Mental Health, An Issue of Primary Care Clinics in Office Practice (The Clinics: Internal Medicine)

Prim Care Clin Office Pract 34 (2007) xi–xii

Preface

Ralph A. Gillies, PhD J. Sloan Manning, MD Guest Editors

Primary care clinicians often provide continuity of care, emphasize prevention, and address chronic illness with their patients. All these endeavors require the active involvement of the patient in treatment planning and adherence. An active and healthy therapeutic alliance that recognizes that patients are the chief consumers of health care is essential in this regard. This critical role in directing one’s health care can be either facilitated or complicated by a patient’s emotional, cognitive, and behavioral strengths or weaknesses (ie, mental health). It is widely recognized that patients who have mental health concerns often present first to their primary care physician, and most continue to receive treatment of their mental concerns (eg, depression, anxiety) in primary care. This reality is compounded because many health conditions that affect a patient’s level of functioning (eg, chronic pain, diabetes, headaches) often have mental health comorbidities that influence the course of illness and treatment. Primary care clinicians are well positioned to identify and assist patients who have mental health concerns. This central or de facto role in mental health care, however, is complicated by factors that hinder the delivery of evidenced-based care that is optimally integrated into the clinical process as a whole. Among the obstacles to such a rational approach to health care are an undue focus on acute rather than chronic health issues; lack of specific training in the recognition, assessment, and management of mental distress or illness; and financial obstacles (mental health carve-outs and other obstacles) that prevent the effective collaboration among diverse health professionals necessary to implement and manage effective treatment. 0095-4543/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pop.2007.06.002 primarycare.theclinics.com

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The articles in this issue present the latest information on mental health problems commonly seen in primary care. Each article offers practical suggestions on how clinicians can address these problems to improve overall care. We hope that the information contained here will be embraced by readers and enrich insight into mental distress and dysfunction as a biopsychosocial phenomenon. It is hoped that someday the fragmentation currently evidenced in health care delivery that hinders integrated and comprehensive approaches will give way to systems that honor mental health as fundamental to health. Ralph A. Gillies, PhD HB-3041 1120 15th St. Department of Family Medicine Medical College of Georgia Augusta, GA 30912-3500, USA E-mail address: [email protected] J. Sloan Manning, MD PrimeCare of Hickory Branch 501 Hickory Branch Road Greensboro, NC 27409, USA Mood Disorders Clinic Moses Cone Family Practice Residency 1125 N. Church Street Greensboro, NC 27401, USA E-mail address: [email protected]

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Attention Deficit/Hyperactivity Disorder in Adults Shannon B. Moss, PhD*, Rajasree Nair, MD, Anthony Vallarino, DO, Scott Wang, MD Baylor Family Medicine Residency at Garland, 601 Clara Barton Boulevard, Suite 340, Garland, TX 75042, USA

Attention deficit/hyperactivity disorder (ADHD), once considered to be a disorder only of childhood, has gained recognition as a legitimate disorder among adults. As professionals’ awareness of this disorder and its concomitant media attention have increased, more adults have begun to identify themselves as having symptoms of adult ADHD, leading them to present to their primary care providers. Many of these providers, however, may be ill-equipped to identify, diagnose, and treat the symptoms of adult ADHD. Reasons for primary care physicians’ lack of comfort in managing ADHD symptoms in adults may be multifactorial, and include high rates of self-diagnosis, lack of guidelines for evaluation and management, higher rates of comorbid psychiatric and substance use disorders, and the need for treatment with drugs of potential abuse [1,2]. The purpose of this article is to present information on the prevalence, clinical presentation and associated features, diagnosis, and treatment of adults who have ADHD, in order to provide primary care physicians with the necessary tools for managing these patients.

Prevalence Prevalence estimates of ADHD in children range between 2% and 18% in community studies. A recent Centers for Disease Control report from the National Survey of Children’s Health (NSCH-2003) indicated that, in 2003, approximately 4.4 million children aged 4 to 17 years had a history of ADHD [3]. Data regarding the persistence of ADHD into adulthood

* Corresponding author. E-mail address: [email protected] (S.B. Moss). 0095-4543/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pop.2007.05.005 primarycare.theclinics.com

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(ie, ADHD symptoms among adults previously diagnosed with childhood ADHD) vary somewhat by study, with reports ranging from 1% to 36% [4–7]. This variation is likely caused by variation in methodology (eg, prospective reports versus meta-analysis) and diagnostic criteria used; however, there is some agreement amongst studies that the number of adults who continue to be functionally impaired because of ADHD symptoms is greater than the number of adults meeting full ADHD diagnostic criteria. For example, though one study found 8% of adults who had been diagnosed with childhood ADHD continued to meet Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) criteria for ADHD in adulthood, an additional 3% reported continued impairment due to sub-threshold ADHD symptoms [7]. Similar results were reported in a later study using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. In a study of ADHD symptom persistence into adulthood, Faraone and colleagues [8] found a persistence rate of 15% at age 25 when full DSM-IV criteria were applied; however, persistence was estimated to be between 40% and 60% when including ADHD in partial remission. Extrapolating from this data and a childhood prevalence of 8%, the study authors estimate adult ADHD prevalence at age 25 to be 1% for the full criteria and an additional 2% for cases in partial remission [8]. This finding is somewhat lower than more recent research suggesting prevalence rates of 4.4% [9]. Further, it appears that those who have more severe childhood ADHD, defined as having both attentional and hyperactive symptoms, are at greater risk for persistence than those who have attentional or hyperactive symptoms alone [6]. As in children, adult ADHD appears to be more commonly identified in males, with reported male-to-female ratios ranging from 1.7:1 to 2.2:1 [10,11].

Pathophysiology The pathophysiology of adult ADHD is not well- understood, but is considered to be multifactorial, consisting of genetic, environmental, and neurobiologic influences. Medications used to treat ADHD influence the dopaminergic and noradrenergic systems of the nervous system, which may give some insight into abnormalities in neurologic pathways and the potential for genetic locus identification. With the emerging trends in genetic evidence, it is increasingly likely that the pathophysiology of ADHD is complex, involving the action of multiple genes and environmental factors. Family studies ADHD is considered a heritable disorder, with approximately 70% heritability, one of the highest among psychiatric disorders [12,13]. In recent years, many family, twin, and molecular genetic studies have shown a strong probability that genetic factors influence the development of ADHD.

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Children of parents who have ADHD have up to a sevenfold increase in their likelihood of developing ADHD when compared with children of non-ADHD parents. Although it is important to understand that to date no single gene has been implicated as the sole cause of ADHD, there is research to support multiple chromosomal sites that may influence the susceptibility of developing ADHD. Specifically, the dopamine receptor gene (DRD4) and the dopamine transporter gene (DAT) have been associated with ADHD [13]. A recent adoption study reinforced the genetic link, finding that adoptive relatives of ADHD-affected children had lower rates of ADHD and other associated conditions than biological relatives of ADHD patients [14]. In a study of monozygotic twins, behavioral discordance was evident at age 2, and low birth weight and delayed motor development were significant markers for development of ADHD [15]. Neuro-imaging of high-risk concordant twins has yielded significant differences in the affected areas of prefrontal lobes compared with discordant twins, further confirming a genetic etiology for the development of ADHD [16]. Environmental factors Although all environmental factors required for emergence of ADHD are not known, several have been implicated, including physical or toxic assaults on the brain and psychological stressors [17]. Prenatal exposure to nicotine has been identified as a significant risk factor for the development of ADHD [15,18–20]. Consumption of alcohol and caffeine and maternal stress during pregnancy have also been implicated in a multitude of studies; however, a recent meta-analysis failed to identify the significance of these factors, mainly because of contradictory and inconsistent findings among studies [20]. Further, exposure to lead, low birth weight, single parenthood, and low parental education levels and socioeconomic status have all been implicated in the etiology of this complex disorder [15,19,21]. Neurobiologic factors Several structural abnormalities in the brain have been documented in patients who have ADHD. In 2003, Sowell and colleagues [22] found a statistically significant correlation between reduced brain volume and ADHD when compared with non-ADHD peers. Specifically, the prefrontal lobe, frontal cortex, cerebellum, and subcortical structures were found to be affected. Further, different areas of the brain were found to be affected in monozygotic discordant and concordant twins, accounting for genetic and environmental factors as etiology for these different structural changes [16]. The concordant high-risk twins showed reduction in brain volume in orbitofrontal subdivision and posterior corpus callosum, whereas the discordant pairs had volume reduction in the right inferior dorsolateral prefrontal cortex.

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Diagnostic criteria Diagnostic and Statistical Manual of Mental Disorders criteria The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for ADHD diagnosis were originally developed for the diagnosis of childhood ADHD. These criteria require either six symptoms of inattention (ie, failure to attend to detail, difficulty sustaining attention, not listening when spoken to, failure to follow through on tasks, organizational deficits, difficulty concentrating, losing items, distractibility, forgetfulness) or hyperactivity/impulsivity (ie, fidgeting, difficulty staying seated, excessive running/climbing, difficulty playing quietly, acts as though ‘‘driven by a motor,’’ excessive talking, difficulty awaiting one’s turn, interrupting frequently, prematurely responding to questions) be present for a diagnosis of ADHD. In addition, the symptoms must result in significant impairment observable in at least two settings, and must be present before age 7. Individuals may be diagnosed with one of the three subtypes: predominantly hyperactive-impulsive type, predominantly inattentive type, and combined type [23]. The use of the DSM diagnostic criteria has been problematic in adults. One of the most significant concerns is the lack of adults in the field trials used to establish the diagnostic criteria for ADHD. In fact, before DSMIV, there was no indication in the diagnostic criteria that ADHD could persist into adulthood; as a result, many of the criteria are not age-appropriate for adults (eg, ‘‘runs or climbs excessively’’) [24]. Though some effort has been made to adjust the criteria to include behaviors more appropriate for adults through the addition of words such as ‘‘work’’ and ‘‘workplace,’’ further studies are still needed to determine if the symptoms of ADHD in childhood are representative of those in adulthood [25,26]. For instance, one study found that several of the DSM criteria did not adequately discriminate between ADHD and non-ADHD adults; criteria found to discriminate between the groups included fidgeting, difficulty remaining seated, difficulty awaiting one’s turn, and engaging in potentially physically harmful behaviors [11]. It is also unclear if the minimum of six criteria for children would result in under-diagnosis when applied to adults, because many ADHD adults learn to compensate for their deficiencies by modifying their environments, relying on others, or choosing careers and lifestyles that more easily accommodate their symptoms [25,27]. Research regarding the validity of minimum criteria for diagnosis is inconsistent to date [28]. One of the most recent studies indicated significant symptom decline with age, particularly with regard to hyperactivity and impulsivity [29]. The study authors caution that, though ADHD adults may not meet full diagnostic criteria, they may continue to experience significant functional impairment because of their residual symptoms and thus warrant treatment.

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Another concern regarding DSM criteria is the age of onset requirement. Adults presenting with ADHD symptoms may have difficulty with the retrospective recall required to meet this criterion and rarely present with elementary school documentation or a family member who can report on their behaviors before age 7 [25,30,31]. The validity of the age of onset criterion has been questioned in prior research, which indicated that a large number of ADHD children did not experience symptoms until after age 7. This was particularly true for those who have ADHD predominantly inattentive type, of whom 75% did not have symptoms until after 9 years of age [32]. This and other research have led some to suggest that the age of onset criterion be modified or eliminated [25,33]. Utah criteria A second set of criteria often used for adult ADHD diagnosis is the Utah Criteria [34,35]. The Utah Criteria require that childhood and adult criteria be met for a diagnosis of ADHD in adults. Childhood criteria include a childhood diagnosis per the DSM-IV, hyperactivity, attention deficits, and one of the following: school behavior problems, impulsivity, over-excitability, and temper outbursts. Adult criteria include motor hyperactivity and attention deficits, and two of the following: labile affect, temper outbursts, excessive emotional reactivity, disorganization, impulsivity, and associated features of ADHD. Per the Utah Criteria, adult ADHD may only be diagnosed in the absence of other psychiatric disorders. One of the most frequent criticisms of the Utah Criteria is its exclusion of inattentive symptoms. This is of particular concern given previous research indicating slower decline of inattentive symptoms as compared with hyperactivity and impulsiveness as ADHD patients age [29]. The inclusion of affective symptoms is also of concern given the many mood disorders that may be characterized by labile mood [25]. Further, requiring that other psychiatric disorders must be absent for ADHD diagnosis would likely result in the under-diagnosis of many symptomatic adults given the high rates of comorbidity of ADHD with other psychiatric diagnoses [36,37]. Clinical presentation With increased public awareness of adult ADHD comes increased self-referral and self-diagnosis in the general population [2]. Many adults begin to suspect they suffer from ADHD during the process of having their children evaluated and treated for ADHD. Whereas children are more likely to be referred for evaluation because of the negative impact their behavior has on others, adults are more likely to seek treatment because of the negative ramifications of their behavior on their own lives, though not all may identify their symptoms as indicative of ADHD [38]. Faraone and colleagues identified the primary presenting complaints of adults diagnosed with

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ADHD, comparing those who suspected themselves of having ADHD and those who did not. Interestingly, both groups presented with similar symptoms, the most common being difficulty concentrating, disorganization, failure to complete projects, inattentiveness, and poor school performance. Affective complaints included anxiety, increased temper, and depression [2]. Other affective complaints, such as hostility and emotional lability, may also prompt adults who have ADHD to seek treatment [11,39,40]. Cognitive complaints, including poor concentration and impaired memory, are common in these patients as well [1,34,37,39,41–43]. Poor academic and work performance may result in part from poor organizational, prioritization and time management skills, and lack of attention to details or over-focus on unimportant details [1,34,37,39–43]. Not surprisingly, these patients also report making a high rate of careless errors and experiencing impatience, low frustration tolerance, and impulsivity [37–39,41–43]. Low self-esteem often accompanies these complaints [40] (Box 1). Associated features and impact In trying to understand adult ADHD more fully, it is worthwhile to examine some of the areas affected by this condition, because functional and Box 1. Clinical presentations of adult ADHD Poor concentration Fidgeting Difficulty remaining seated Impulsivity (eg, difficulty awaiting one’s turn) General disorganization Failure to complete projects Inattention Poor school and work performance Poor time management Poor anger management Cognitive impairment Anxiety/depression Hyperfocused Substance abuse Hostility Emotional lability Low self-esteem Problems in family and relationships (divorce, separation) Increased rate of motor vehicle accidents Adapted from Refs. [1,2,11,37–43].

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psychosocial deficits present substantial difficulties in various aspects of the lives of ADHD adults. Academic and work performance The aforementioned deficits may lead ADHD adults to complain of poor work performance or academic underachievement, which in school may be accompanied by more grade retention, higher drop-out rates, lower grade point averages, increase probation rates, and poor college adjustment [12,44–47]. Additionally, 20% of ADHD patients may have auditory processing deficits [12]. At work, symptoms may result in higher rates of unemployment, frequent job changes, lower occupational status, and more work absences, which in turn results in lower socioeconomic status [7,11,34,37,39,42,45,48–51]. Social interactions Strained relationships with spouses, other family members, friends, and coworkers may result from a lack of understanding of the disorder and frustration with the symptoms [11,35,37,39]. In the workplace, inattention, procrastination, and attention to insignificant detail can lead to frequent frustration and strained relationships. For example, the inability of adults who have ADHD to manage time appropriately and needing to enlist coworkers to assist in task completion can cause workplace conflict, as can difficulty monitoring and inhibiting their own behavior (eg, interrupting, excessive talking) and engaging in socially inappropriate behavior (eg, explosive outbursts, making rude comments, engaging in phone conversations during meetings) [1,2,12,38]. Their interpersonal difficulties may contribute to conflicts in social acceptance, with ADHD patients exhibiting poorer social skills and self-esteem than their non-ADHD peers [47,52–54]. Family and romantic relationships can be strained as well, as demonstrated by higher rates of separation and divorce among ADHD patients and lower rates of marital, family, and social life satisfaction [11,45,54]. Common complaints include not listening to or interrupting others, inattentiveness to others’ emotional needs, disorganization in managing household responsibilities (eg, finances), and poor communication and problem-solving [55]. The presence of an ADHD child can compound the family strain. The chance of an adult ADHD patient having children who share their diagnosis is approximately 50%, which may result in a chaotic household when symptoms are not well-controlled [2]. Driving Adults who have ADHD exhibit a significantly higher rate of traffic accidents and greater rates of damage in such accidents as compared with nonADHD adults. Barkley and colleagues found that adolescents who had

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ADHD were four times more likely to have had a motor vehicle accident than their non-ADHD peers [56]. Their data also found that ADHD adolescents were more likely to have driven an automobile before being of legal driving age, less likely to employ sound driving habits, more likely to have had their licenses suspended or revoked, and more likely to have received repeated traffic citations (mostly for speeding). These driving problems are reportedly apparent to others as well as the patients themselves [11,57]. Substance abuse ADHD patients are more likely to develop substance abuse, and at an earlier age, than those who did not have ADHD [58,59]. The risks of substance abuse are further increased by the presence of comorbid bipolar or conduct disorders [7]. Several reasons for the elevated substance abuse rates have been proposed, including self-medication of ADHD symptoms and gaining social acceptance [60]. Unfortunately, ADHD adults have lower remission rates and longer periods of substance abuse than their non-ADHD peers [26,61]. Health care costs It is interesting to note that people who have ADHD have higher health care costs than non-ADHD individuals. A comparison of 9-year median medical costs between the two groups indicated ADHD medical costs as $4306 versus non-ADHD medical costs of $1944 [62]. Similar findings were reported by Secnik and colleagues [49], who found significantly greater outpatient, inpatient, prescription, and total health care costs among ADHD individuals as compared with non-ADHD individuals. Higher rates of substance abuse treatments and increased treatment frequency because of noncompliance with medical recommendations may contribute to these health care costs [52]. Further, health care costs of ADHD patients’ family members are also higher, which may be caused by elevated stress, depression, and substance abuse found in these families [52,63].

Assessment Whereas primary care physicians often recognize and treat ADHD in children, they may experience difficulties in identifying and diagnosing the disorder in adults. As of this writing, there are no tests diagnostic for ADHD; however, a thorough history accompanied by questionnaire and checklist data can be beneficial in clarifying the diagnosis. Neuropsychological assessment may also help elucidate patients’ deficits and provide target areas for treatment. It should also be noted that, in addition to the approaches below, patients should be screened for other psychiatric disorders, given their high rates of comorbidity with ADHD.

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Interviews The first step in conducting an ADHD assessment is a thorough interview. Patients should be queried about ADHD symptoms, both past and present. Murphy and Schachar [64] recommend asking specific questions rather than open-ended questions to improve the accuracy of retrospectively reported symptoms. Patients should be asked to provide an educational and occupational history, including conduct and disciplinary actions, to determine if symptoms (eg, losing homework, difficulty staying in one’s seat, excessive talking, difficulty playing quietly) of ADHD were present in childhood, and to discern the functional impact of the symptoms on performance [1,65]. When possible, collateral information should be obtained; this may be done by way of reviewing school records or seeking input from patients’ family members [1,65]. Input from each of these sources can provide information on the presence of ADHD symptoms during childhood as discussed above; further, family members may be able to provide information on current symptoms and functioning. Questioning patients about their performance in a variety of situations during the prior week, the level of effort required to function, and coping strategies used may also provide valuable information regarding functional impairment [40,65,66]. Given the heritability of ADHD, assessing family history of ADHD may provide insight into the patient’s presenting symptoms [42]. Although not necessary for obtaining a history of ADHD symptoms, diagnostic interviews are available to assist with the interview process, including the Brown Attention Deficit Disorder (ADD) Scale, Conners’ Adult ADHD Diagnostic Interview for DSM-IV, and the Diagnostic Interview Schedule [40]. Rating scales Several rating scales are available to assist with adult ADHD diagnosis. Research indicates significant positive correlations between ratings of adults who have suspected ADHD and their significant others [11,41,67]; however, they should not be used alone as diagnostic tools because of unacceptable rates of false positives [26,68]. Many of the available rating scales use Likert-type scales to assess symptoms, have acceptable psychometric properties, can be administered in 5 minutes or less, and require no additional training of the administrator (eg, Brown ADD Scale for Adults, Conner’s Adult ADHD Rating Scale, Adult ADHD Self Report Scale, ADHD Rating Scale-IV) [26,69,70]. Scales such as Connor’s Adult ADHD Rating Scales can be administered to a spouse or parent, and thus can assist in gathering collaterals’ views of patients’ symptoms. The Wender Utah Rating Scale, based on the aforementioned Utah Criteria, takes 10 minutes to administer and is also commonly used [35]; however, criticism of this scale is similar to that of the Utah criteria on which it is based, with research indicating that it measures affective and conduct disorders not specific to ADHD and lacks field testing [71,72].

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Neuropsychological assessment Compared with non-ADHD adults, ADHD adults exhibit significant deficits in a variety of functional domains and on specific neuropsychological tests. For example, meta-analyses of neuropsychological performance differences between ADHD and non-ADHD adults have revealed deficits in verbal memory, focused and sustained attention, behavioral inhibition, and abstract problem solving among ADHD adults [73,74]. Reviews of the literature suggest that specific neuropsychological assessments found to discriminate between the two groups include continuous performance tasks, the Stroop task, Trail Making Tasks, the Controlled Word Association Test, and Weschler intelligence measures, with most effect sizes being moderate [75,76]. The Digit Symbol subtest of the Weschler intelligence scale appears to be the most effective subtest for identifying ADHD adults, particularly when used in combination with the Arithmetic subtest [75–77]. Both the Digit Symbol and Arithmetic subtests are measures of working memory, which suggests that other assessments of working memory may also be sensitive to ADHD in adults. As with rating scales, there are no neuropsychological assessments to date that are diagnostic of adult ADHD. Despite this, neuropsychological assessment can assist patients with legal services, such as seeking accommodations through the Americans with Disabilities Act, and targeting deficient areas for treatment and vocational counseling [66,78]. Laboratory and radiological tests Routine laboratory and radiological tests are useful for differentiating ADHD from common medical conditions that can mimic symptoms of ADHD. Common laboratory tests include complete blood count, metabolic profile, including liver function tests, and thyroid function studies. Serum lead level and heavy metal screening should be undertaken if history warrants. Serum vitamin B12 level should be obtained in patients who have anemia, nutritional deficiencies, and cognitive impairment. Electroencephalogram and computed tomography of the head should be performed in patients who have a recent history of trauma to the head or history suggestive of seizure disorders. In patients who have concurrent sleep disorder symptoms, polysomnography should be undertaken to rule out obstructive sleep apnea (OSA) as the etiology for ADHD symptoms [1,79].

Comorbidity Psychiatric comorbidity is significantly higher in ADHD adults as compared with non-ADHD controls, and may often be the primary concern with which patients present to their primary care providers [36,37]. Biederman and colleagues [53] found that 44% of a sample of ADHD adults had

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at least one comorbid psychiatric diagnosis. Mood disorders are among the most commonly reported comorbidities in the literature, and occur at significantly higher rates in ADHD adults as compared with controls [11,49,80,81]. Rates of major depressive disorder among adult ADHD samples range from 11.5% to 53.5%, and dysthymia rates range from 11.5% to 25% [9,41,82– 84]. Rates of bipolar disorder and cyclothymia are reported to be 19.4% and 25%, respectively [9,82]. The high rate of mood disorders in this population may be caused in part by the difficulties of living with the symptoms of ADHD; however, it is not possible to attribute causality, because the cause for each disorder is likely multifactorial [39]. It is important that comorbid psychopathology be identified, given that failure to identify bipolar illness or misattributing mood symptoms solely to ADHD may lead to iatrogenic worsening of a bipolar disorder treated with antidepressants or psychostimulants. Anxiety disorders are also commonly reported at a greater rate among ADHD adults than controls [49,53,80,81]. For example, rates of generalized anxiety disorder range from 8% to 53% among ADHD adults [9,82,83]. Similarly, agoraphobia, panic disorder, post-traumatic stress disorder, social phobia, and specific phobia have been noted to occur at higher rates among ADHD adults than non-ADHD peers [9,54]. Antisocial disorder, conduct disorder, and oppositional defiant disorder among ADHD adults have also been frequently investigated. The majority of research to date indicates a higher rate of each of these disorders among ADHD adults [7,11,41,49,53,81]. One study suggests that the prevalence of comorbid antisocial personality disorder in ADHD adults is tenfold compared with non-ADHD peers [7]. Both conduct disorder and antisocial personality disorder have been found to be more common in adult ADHD males than females [54]. Rates of substance use have also been found to occur at significantly higher rates among ADHD adults versus non-ADHD adults, with one study reporting a five times greater risk [7,9,11,41,49,53,81]. Identified substances of abuse have included alcohol, cannabis, and amphetamines [84]. Some gender differences have been identified, with males exhibiting significantly greater rates of alcohol abuse than females [54]. One potential explanation for the elevated rates of substance use is self-medication of untreated ADHD symptoms [43]. It is also possible that impulsivity characteristic of ADHD contributes to higher rates of abuse in this population. Other disorders identified more frequently among ADHD adults include enuresis, stuttering, speech and language disorders, and tics [53,54].

Differential diagnosis ADHD should be considered in the differential of any condition presenting with complaints of inattention, fatigue, and hyperactivity, as well as in

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patients presenting with depression, anxiety, substance abuse or bipolar disorder [2,53] (Table 1). Medical diagnoses A complete history and physical examination should be conducted in patients presenting with symptoms of ADHD. A medical diagnosis should be suspected particularly in patients with recent onset of symptoms. The most common disorders that may present with symptoms similar to those of ADHD include thyroid disorders (hypo- and hyperthyroidism), seizure disorders (petit mal or partial complex), drug interactions, hepatic diseases, lead toxicity, post-head injury and hearing deficits [1]. Sleep-disordered breathing, OSA, has been found to present with sleep disturbances, inattention, and cognitive impairment, which resolve with treatment for OSA. Hence, OSA should be considered in the differential of patients who have ADHD and who have symptoms of snoring, excessive daytime somnolence, inattention, and memory difficulties [79]. Psychiatric diagnoses Given the frequency of comorbid psychiatric diagnoses with ADHD and its symptoms overlapping with other psychiatric diagnoses (eg, poor concentration, restlessness, talkativeness), conducting a thorough history and symptom evaluation is paramount. Mood disorders share many symptoms with ADHD. For example, both major depressive disorder and ADHD share symptoms of decreased concentration, attention, and memory; however, unlike ADHD, major depressive disorder is marked by neuro-vegetative symptoms (eg, anhedonia and appetite disturbance) [1,48]. Questioning the patient about the course of symptoms to determine if cognitive symptoms occur in the absence of mood symptoms can also clarify the diagnosis [66]. Bipolar disorder and ADHD also share common symptoms, including Table 1 Differential diagnosis of adult ADHD Medical

Psychiatric

Thyroid disorders (hypo/hyperthyroidism) Head trauma Obstructive sleep apnea Seizure disorders (petit mal or partial complex) Vitamin B12 deficiency Drug interactions Heavy metal poisoning Hearing deficits Liver disease Lead toxicity

Major depression Bipolar disorders Generalized anxiety disorder Substance abuse and dependence

Adapted from Refs. [2,79,85].

Personality disorders (antisocial and borderline)

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hyperactivity, decreased attention, and mood lability [1]. Excessive spending, delusions or other psychotic symptoms, grandiosity, racing thoughts, and decreased need for sleep help differentiate ADHD from mania or hypomania. Anxiety disorders (eg, generalized anxiety disorder) share attention and concentration deficits with ADHD, but excessive worry and somatic symptoms seen in these disorders are not characteristic of ADHD [1,66]. Personality disorders must also be differentiated from ADHD. Borderline personality disorder, like ADHD, is characterized by impulsivity, mood lability, and hostility [48]; however, these symptoms in ADHD patients are typically intermittent, shorter in duration, and less severe. Further, ADHD is not characterized by the dichotomous thinking, abandonment fears, or self-injurious behavior seen in borderline personality disorder [48]. Antisocial personality disorder shares impulsivity and affective lability with ADHD; however, an arrest history and lack of insight into and remorse regarding the behaviors seen in antisocial personality disorder can assist in differentiating the two disorders [1,85] (Table 2).

Treatment The mainstay of adult ADHD treatment includes pharmacological interventions, behavioral interventions, or a combination of both, with the goals of symptom remission and return to full social functioning. Studies in children indicate that combined treatment results in greater symptom improvement and is superior to pharmacotherapy alone, especially in improving non-ADHD symptoms and functional impairment [86]. Multiple other studies comparing cognitive-behavioral therapy to pharmacological management indicate that cognitive-behavioral therapy alone may be insufficient, and that combined treatment is more effective than either treatment alone in control of symptoms and improving functional status [80,83,87]. Table 2 Differentiating ADHD from other psychiatric diagnoses Psychiatric diagnosis

Distinguishing characteristics

Major depressive disorder

Neuro-vegetative symptoms (eg, anhedonia, appetite disturbance) Excessive spending Delusions Insomnia Excessive worry Somatic complaints Dichotomous thinking Abandonment fears Self-injurious behavior Arrest history Lack of insight into and remorse for behaviors

Bipolar disorder

Anxiety disorders Borderline personality disorder

Antisocial personality disorder Adapted from Refs. [1,48,66,85].

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Pharmacological As in childhood ADHD, medications, especially central nervous system stimulants, have shown to significantly improve adult ADHD symptoms [88–91]. Much of the evidence for adult ADHD treatment is based on treatment efficacy in children and adolescents; long-term data are lacking in the treatment of adult ADHD. The presence of psychiatric and medical comorbidities and substance abuse in adults who have ADHD makes drug choices difficult. Patients should be counseled that medications provide only symptomatic relief, and that concurrent psychotherapy and counseling are recommended to acquire necessary organizational and social skills for independent adult functioning. Although stimulants are effective in ADHD treatment, physicians’ concerns about the use of controlled substances with abuse potential play a significant role in the choice of medications. In a recent survey, 38% of physicians responded that they prefer prescribing a nonstimulant medication, and 58% preferred prescribing a noncontrolled medication without evidence of abuse potential [92]. In 2003, atomoxetine, a nonstimulant, was the first drug to receive United States Food and Drug Administration (USFDA) approval for the treatment of adult ADHD. Stimulants Stimulants are typically the first-line agents used in the treatment of adult ADHD [89–91]. Patients who have moderate to severe impairment in two different settings (occupational, social, academic, and family) should be considered for treatment with stimulants [89]. Methylphenidate (MPH), dextroamphetamines (DEX), mixed amphetamine salts (levoamphetamine and dextroamphetamine) (AMP) and pemoline are the stimulants commonly used in the treatment of adult ADHD [89]. They act by blocking the reuptake of dopamine and norepinephrine, resulting in their accumulation in the presynaptic cleft. Amphetamines also increase these neurotransmitter levels in the presynaptic cleft by direct release of dopamine and norepinephrine. MPH and amphetamines are the most commonly used agents in the treatment of adult ADHD, with no significant differences in efficacy, side-effect profiles, and response rates [87,89]. Pemoline, a weak stimulant, has been withdrawn from the market amid concerns of increased risk of hepatotoxicity [93]. Earlier studies in adults showed a lesser stimulant response rate in adults compared with children, with rates ranging from 25% to 78% [88,94,95]. This difference in clinical response could be caused by the diagnostic criteria used, insufficient doses of medication, and the presence of comorbid psychiatric disorders. Recent studies with higher doses of stimulants (1.1 mg/kg/ day of MPH) have shown more than 75% therapeutic response in ADHD symptoms [96–98]. Similar results were described by Weisler and colleagues [98] using mixed amphetamine salts.

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Stimulants have an immediate onset of action, and extended-release formulations should be used whenever possible to increase compliance, provide longer duration of symptom relief, and decrease the potential for abuse. Some of these are Concerta (McNeil Pediatrics, Fort Washington, Pennsylvania), Adderrall XR (Shire, Wayne, Pennsylvania), and Ritalin LA (Novartis, East Hanover, New Jersey). Patients should be initiated on the lowest dose available and titrated up until symptom relief is obtained with least side effects. Patients who fail to have a response to one group should be tried on the other before initiating second line treatments [89]. Most patients on stimulant therapy take ‘‘drug holidays’’ on weekends and on vacation, mainly from concerns of adverse effects; however, there are no significant data on the efficacy of this practice, and it should not be advocated to patients [2,89]. In addition to relief of ADHD symptoms, stimulants have been shown to improve self-esteem, cognition, and social and family functioning [89]. They also have shown improvement on comorbid anxiety, conduct, and tic disorders [89]. Further, stimulants have a protective effect against substance abuse and improve driving skills [99,100]. A recent meta-analysis of six studies (two with follow-up in adolescence and four in young adulthood) showed a 1.9-fold reduction in risk for substance use disorders and later drug and alcohol use disorders in youths who were treated with stimulants compared with youths who did not receive pharmacotherapy for ADHD [99]. Nonstimulants Nonstimulants are typically used to treat patients who do not tolerate stimulants, or who have comorbid psychiatric or medical conditions in which stimulants are contraindicated [89]. These agents can be used in combination with stimulants to treat comorbid psychiatric disorders and may help in decreasing the stimulant dose required. Commonly used medications include atomoxetine, tricyclic antidepressants (TCAs), and buproprion. Atomoxetine, a norepinephrine reuptake inhibitor, is the first drug to receive USFDA approval for the treatment of adult ADHD. Earlier studies of atomoxetine in children have shown similar efficacy and tolerability compared with stimulants [87,90]. Two large, multicenter, randomized control trials of 10 weeks duration using atomoxetine indicated reduction of inattentive and hyperactive and impulsive symptoms, with less than 10% discontinuation rate caused by adverse effects [101]. It has been increasingly used in patients who have comorbid anxiety disorders, substance use disorders, and tics. A use study for treatment initiation with atomoxetine indicated that patients were more likely to receive atomoxetine than a stimulant if they had a psychiatric diagnosis or alcohol dependence [102]. Atomoxetine has the added benefit of not being a controlled substance and having no abuse potential. Most of the evidence on TCA efficacy for ADHD is based on child and adolescent studies. For example, in one study, desipramine at a target dose of 200 mg yielded a 68% response rate over placebo in a 6-week period

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[103]. Most common adverse effects include cardiac side effects, increased seizure risk, dry mouth, and constipation. Buproprion is an antidepressant with dopamine and noradrenergic agonist effects. It has been shown to be efficacious as a second-line agent in the treatment of ADHD, especially in patients who have comorbid bipolar disorder, depression, or substance abuse [104]. In a 6-week trial comparing patients receiving sustained-release bupropion (up to 200 mg twice a day) to patients receiving placebo, bupropion treatment was associated with a 42% improvement in ADHD symptoms, compared with 24% reduction in placebo [105]. Other rarely used nonstimulant medications include mono amino oxidase inhibitors, clonidine, and cholinergic agents with structural similarities to nicotine (ABT-418) [106]. Clondine may also be used as an adjunct to stimulants in the treatment of comorbid aggression and insomnia [89]. Adverse effects Most common side effects of stimulants are mild and include disturbances of sleep, appetite and mood, weight loss, nervousness, irritability, agitation, and confusion [87,89,96]. Most of these side effects can be effectively managed by giving medications with meals, lowering the dose, changing the timing of administration to earlier in the day, or using long-acting preparations [89]. Stimulants are contraindicated mainly in patients who have previous history of sensitivity, glaucoma, hyperthyroidism, hypertension, and acute psychosis. Further, they should be used with caution in patients who have a prior history of abuse of stimulants [89]. MPH and bupropion may cause seizures in adults who have seizure disorders; hence, these patients should be stabilized with anti-seizure medications before using higher doses of medications [89]. Stimulant and nonstimulant medications may also be associated with increased rates of cardiovascular side effects, such as palpitation, tachycardia, and hypertension, because of their pressor and chronotropic effects; hence, close monitoring of vitals should be done before the initiation of treatment and at periodic intervals [96,107–109]. In 2006, the USFDA issued a warning on all stimulants, prompted by sudden unexpected deaths in children and adolescents using stimulants between 1999 and 2003 [110]. They recommend against the use of stimulants in children or adolescents who have known serious structural cardiac abnormalities, cardiomyopathy, heart rhythm abnormalities, or other serious cardiac disorders. Further, the American Heart Association suggests careful evaluation for cardiac disease before initiation of stimulant therapy in adults. They recommend careful evaluation of patients’ family histories for sudden death at less than 40 years of age, long QT Syndrome, cardiac arrhythmias, hypertrophic cardiomyopathy and personal history of heart disease, symptoms of palpitation, dizziness, or syncope [111]. A basal electrocardiogram before the initiation of medications (especially TCAs) may be useful in monitoring of these patients.

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In 2006, the USFDA also issued a warning on all stimulants and atomoxetine because of the potential for psychotic or manic symptom development, especially in children and adolescents. Atomoxetine may also increase suicidal thoughts and thus carries an additional USFDA warning [112]. Hence, patients should be closely monitored for behavior change, psychosis, and suicidal ideation while on treatment with these medications. Nonpharmacological Numerous strategies for assisting ADHD adults in managing their symptoms have been suggested anecdotally; however, there is a paucity of research investigating the benefits of nonpharmacologic interventions [113]. The most frequently researched interventions are cognitive-behavioral, offered both in individual and group formats, and with and without pharmacological treatment. Cognitive-behavioral therapy includes identification and modification of patients’ maladaptive thought patterns and instruction in behavioral modifications to minimize functional impairment [114]. Data indicate that cognitive-behavioral therapy results in statistically significant improvements in ADHD symptoms, functional impairment, depression, anxiety, hopelessness, health status, and self-esteem [80,83,115,116]. Skills typically taught during cognitive-behavioral therapy include psychoeducation about ADHD symptoms and medications, strategies for improving motivation, concentration (eg, minimizing distractions, self-monitoring), listening, impulsivity, organization and time management (eg, using a calendar, making lists; working during personally optimal times of day), emotional regulation, self-esteem, problem-solving skills, and mindfulness [1,37,80,115,116]. Additional specific recommendations are listed in Box 2. Other strategies recommended to assist ADHD adults include couples/family therapy and support groups, such as the Attention Deficit Disorder Association (www.add.org) and Children and Adults with Attention Deficit Disorder (www.chadd.org) [34,117,118].

Special considerations Primary care/psychiatry Adult ADHD is often under-diagnosed. In one study, only 25% of adults who had ADHD were diagnosed in childhood, even though retrospective assessments supported the presence of childhood ADHD. One potential explanation for under-diagnosis of adult ADHD is primary care physicians’ lack of knowledge of ADHD presentation in adults. Rates of adult ADHD identification are significantly higher among psychiatric settings as compared with primary care settings (52% versus 27%), and ADHD is recognized at younger ages in primary care settings [2]. Education and training may be necessary to overcome this discrepancy [2].

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Box 2. Strategies for management of ADHD symptoms Behavioral strategies  Minimize distractions (eg, no clutter on desk, no working near windows)  Develop a daily routine  Use a calendar to schedule activities  Make ‘‘to do’’ lists, and keep them in sight  Keep note pads available to write down things to remember  Use a filing system  Take time each evening to prepare for the next day  Work at personally optimal times of day  Break large tasks down into smaller tasks and create respective deadlines  Prioritize tasks  Consider and determine pros and cons of multiple options before acting  Delegate tasks when necessary  Ask friends or family to remind of dates and deadlines  Take a ‘‘time out’’ when becoming upset or frustrated  Make multiple sets of keys Other beneficial strategies  Educate patient about ADHD symptoms and medications  Anger management  Mindfulness training (eg, meditation)  Encourage patient to reward self for positive changes and symptom management Adapted from Refs. [2,37,38,80,114,115,117–119].

Substance abuse ADHD symptoms, such as poor impulse control, may present unique challenges to treatment, especially in patients with concurrent substance abuse [60,120,121]. Early treatment of ADHD, with concomitant management of substance abuse, may result in increased rates of compliance and abstinence [60,120,121]. Stimulants should be used with caution in patients who have history of stimulant abuse or dependence [89]. Recent studies of long-acting stimulants in patients who had ADHD and history of substance abuse yield positive effects, with no significant increase in substance abuse [120,121]. In patients who have concurrent substance abuse, atomexitine, desipramine, and bupropion may be preferable to methylphenidate because they are associated with a decreased risk of abuse [26]. When treating

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patients who have concurrent substance abuse, increased vigilance is advised to include compliance evaluation, random drug screens, and coordination with addiction counselors [122]. Pregnancy and lactation There is little known about the effect of ADHD treatment on pregnancy and lactation. Patients who have ADHD have 38% more unplanned pregnancies, and more and more young adults who have ADHD present to primary care physicians for preconception counseling [12]. All stimulants and nonstimulants except bupropion are pregnancy category C (ie, inability to rule out risk); however, there is no indication for therapeutic termination of pregnancy for patients who become pregnant on ADHD medication. Further, abrupt withdrawal of psychotropic medications upon diagnosis of pregnancy may result in unfavorable physiological effects and possible reemergence of symptoms [123]. Therefore, each patient should be properly counseled regarding risks and benefits of treatment, and patients wishing to discontinue or change medications should be closely monitored. A recent evaluation by the National Toxicology Program Center for the Evaluation of Risks to Human Reproduction concluded that there are insufficient data associating methylphenidate therapy in pregnant women and pregnancy loss and reproductive effects in humans [124]; however, a similar study of amphetamines and methamphetamine [125] revealed potential neurobehavioral alterations, low birth weight, and shortened gestation. A confounding effect of other potential drug use could not be ruled out in these patients. The effects of stimulant and nonstimulant medications on lactation are still unknown, and amphetamines and methylphenidate are contraindicated by American Academy of Pediatrics during lactation [126] (Table 3).

Pearls Adult patients who present with cognitive complaints (including inattention), mood complaints, and functional impairment in school, work, and interpersonal relationships may be exhibiting ADHD symptoms. Assessment of adult ADHD should include educational and occupational history, collateral information (both from significant others and school records when available), and assessment of prior and current functional impairment. Diagnostic interviews and rating scales may facilitate this process. Neuropsychological testing may be helpful for treatment planning, vocational counseling, and assisting patients with legal services. Assessment for adult ADHD should include assessment of mood, anxiety, and personality disorders, and substance abuse caused by high rates of comorbidity and symptom overlap.

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Table 3 Treatment of adult ADHD Duration of action

Dose

Side effects

Comments

Methylphenidate (MPH) Short-acting: (Ritalin, Methylin)

3–5 h

10–80 mg/day

Titrate dose weekly by 5–10 mg. Monitor pulse rate and Blood pressure. Pregnancy risk: category Ca Contraindicated in lactation.

Intermediate-acting: (Ritalin SR, Methylin ER, Metadate ER)

3–8 h

20–80 mg/day

Insomnia Loss of appetite Weight loss Headache Nervousness Increase in pulse rate and blood pressure

Long-acting: (Metadate CD, Ritalin LA) Concerta Daytrana (patch) Dextroamphetamine (DEX) Short-acting (Dexedrine)

8–12 h

10–80 mg/day

10–12 h 10–12 h

18–72 mg/day 10–60 mg/day patch

4–6 h

5–45 mg/day

Long-acting (Dexedrine spansules)

6–8 h

5–45 mg/day

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Patch on for 9 hours and off for 15 h. Insomnia Loss of appetite Weight loss Headache Nervousness Increase in pulse rate and blood pressure

Titrate by 5 mg per week. Pregnancy category C Monitor blood pressure and pulse.

4–6 h

5–40 mg/day

Adderall XR

8–10 h

5–60 mg/day

Bupropion (Wellbutrin)

12 h

37.5–450 mg/day

Atomoxetine (Strattera)

24 h

40–80 mg/day

Insomnia Loss of appetite Weight loss Headache Nervousness Palpitation, tachycardia, elevation of blood pressure Insomnia Increased risk of seizures Headache Sleep disturbance Nausea Vomiting Dyspepsia Abdominal pain Headache Changes in blood pressure and pulse rate Jaundice and hepatotoxicity

Pregnancy category C Monitor blood pressure and pulse. Dosing in the morning to reduce sleep disturbances. Titrate by 2.5–5 mg per week.

Pregnancy category B Effect on lactation unknown. Contraindicated in patients with seizures and bulimia. Response after 4–5 weeks Pregnancy category C Effect on lactation unknown. Should be discontinued in patients who develop jaundice or have elevated liver function tests.

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Table 3 (continued ) Duration of action

Dose

Side effects

Comments

Tricyclic antidepressants (TCA) Desipramine or imipramine

24 h

10–150 mg/day

Dry mouth Constipation Changes in pulse rate, blood pressure Conduction abnormalities

Monitor therapeutic levels. Response after 4 weeks Monitor ECG before and after stabilization on treatment.

Insomnia Weight loss Decreased appetite Headaches Nervousness Hepatotoxicity

Pregnancy Category B Effect on lactation unknown. Withdrawn from the market because of hepatotoxicity. Monitor liver function tests.

a

10–150 mg/day 37.5–75 mg/day

FDA use in pregnancy ratings: category A, no risk indicated in controlled studies; B, no evidence of risk in humans; C, inability to rule out risk; D, positive evidence of risk; X, contraindicated in pregnancy. Data from Refs. [2,88,89].

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Nortriptyline (Pamelor) Pemoline (Cyclert)

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A retrospective diagnosis of childhood ADHD should be investigated in all adult patients diagnosed with adult ADHD, and may be facilitated by open-ended questions and structured interviews. Prenatal tobacco exposure has been documented to be a significant risk factor in the development of ADHD. Stimulants (methylphenidate and amphetamine) are the first-line agents in the treatment of adult ADHD. Stimulants and nonstimulant medications used in the treatment of ADHD may cause changes in pulse rate and blood pressure. Hence, vitals should be monitored before the starting of medications and at periodic intervals. Stimulants should not be used in patients who have underlying cardiac disorders, or in patients who have positive family history of sudden cardiac death, other severe cardiac arrhythmias, and structural abnormalities. Atomoxetine and stimulants can induce mania, psychosis, and suicidal ideations; thus, ADHD patients should be closely monitored for behavioral changes. Summary The diagnosis and treatment of adult ADHD can be daunting for primary care providers. One factor contributing to this is the lack of criteria based on field studies with adults, rather than extrapolated from childhood symptom data; however, recent research has provided indications that, though the symptom presentation may change somewhat over time, many of the characteristics of adult ADHD are similar to those manifested in childhood. Providers’ awareness of these changes in presentation and familiarity with strategies that can be easily implemented in the primary care setting are necessary to insure that symptomatic adults are identified. Further, providers must be aware that symptoms commonly attributed to mood, anxiety, and personality disorders may be indicative of adult ADHD, and therefore warrant careful evaluation. By obtaining a childhood history, collateral information on childhood and current functioning (when possible), and assessing current symptoms, providers will be able to identify these patients and provide treatment, including facilitating interventions to minimize patients’ functional impairment (eg, psychological intervention, vocational counseling). References [1] Faraone SV, Spencer TJ, Montano CB, et al. Attention-deficit/hyperactivity disorder in adults: a survey of current practice in psychiatry and primary care. Arch Intern Med 2004;164(11):1221–6. [2] Searight HR, Burke JM, Rottnek F, Adult ADHD. evaluation and treatment in family medicine. Am Fam Physician 2000;62:2077–86.

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[3] Mental Health in the United States: prevalence of diagnosis and medication treatment for attention-deficit/hyperactivity disorderdUnited States, 2003. Centers for Disease Control. Morbidity and mortality weekly report [monograph on the Internet]. Washington: Centers for Disease Control; 2005. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/ mm5434a2.htm. Accessed March 9, 2007. [4] Hill JC, Schoener EP. Age-dependent decline of attention deficit hyperactivity disorder. Am J Psychiatry 1996;153:1143–6. [5] McCormick LH. Adult outcome of child and adolescent attention deficit hyperactivity disorder in a primary care setting. South Med J 2004;97(9):823–6. [6] Kessler RC, Adler LA, Barkley R, et al. Patterns and predictors of attention-deficit/hyperactivity disorder persistence into adulthood: results from the National Comorbidity Survey replication. Biol Psychiatry 2005;57:1442–51. [7] Mannuzza S, Klein RG, Bessler A, et al. Adult outcome of hyperactive boys: educational achievement, occupational rank, and psychiatric status. Arch Gen Psychiatry 1993;50: 565–76. [8] Faraone SV, Biederman J, Mick E. The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med 2006;36:159–65. [9] Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey replication. Am J Psychiatry 2006;163:716–23. [10] Biederman J, Faraone SV, Monuteaux MC, et al. Gender effects on attention-deficit/hyperactivity disorder in adults, revisited. Biol Psychiatry 2003;55:692–700. [11] Murphy K, Barkley RA. Attention deficit hyperactivity disorder in adults: comorbidities and adaptive impairments. Compr Psychiatry 1996;37(6):393–401. [12] Barkley RA, Murphy KR. Attention-deficit/hyperactivity disorder: a clinical workbook. 2nd edition. New York: Guilford Publications, Incorporated; 1998. [13] Faraone SV, Perlis RH, Doyle AE, et al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 2005;57(11):1313–23. [14] Sprich S, Biederman J, Crawford MH, et al. Adoptive and biological families of children and adolescents with ADHD. J Am Acad Child Adolesc Psychiatry 2000;39:1432–7. [15] Lehn H, Derks EM, Hudziak JJ, et al. Attention problems and attention-deficit/hyperactivity disorder in discordant and concordant monozygotic twins: evidence of environmental mediators. J Am Acad Child Adolesc Psychiatry 2007;46(1):83–91. [16] van ’t Ent D, Lehn H, Derks EM, et al. A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: evidence for genetic and environmental heterogeneity in the developing brain. Neuroimage 2007;35(3):1004–20. [17] Faraone SV, Biederman J, Spencer T, et al. Attention-deficit/hyperactivity disorder in adults: an overview. Biol Psychiatry 2000;48:9–20. [18] Mick E, Biederman J, Prince J, et al. Impact of low birth weight on attention-deficit hyperactivity disorder. J Dev Behav Pediatr 2002;23:16–22. [19] Braun JM, Kahn RS, Froehlich T, et al. Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect 2006;114(12): 1904–9. [20] Linnet KM, Dalsgaard S, Obel C, et al. Maternal lifestyle factors in pregnancy risk of attention deficit hyperactivity disorder and associated behaviors: review of the current evidence. Am J Psychiatry 2003;160(6):1028–40. [21] St Sauver JL, Barbaresi WJ, Katusic SK, et al. Early life risk factors for attention deficit/ hyperactivity disorder: a population-based cohort study. Mayo Clin Proc 2004;79(9): 1124–31. [22] Sowell ER, Thompson PM, Welcome SE, et al. Cortical abnormalities in children and adolescents with attention-deficit hyperactivity disorder. Lancet 2003;362:1699–707. [23] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edition. Washington, DC: American Psychiatric Association; 2000.

ATTENTION DEFICIT HYPERACTIVITY DISORDER IN ADULTS

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[24] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edition. Washington, DC: American Psychiatric Association; 1994. [25] McGough JJ, Barkley RA. Diagnostic controversies in adult attention deficit hyperactivity disorder. Am J Psychiatry 2004;161:1948–56. [26] Kalbag AS, Levin FR. Adult ADHD and substance abuse: diagnostic and treatment issues. Subst Use Misuse 2005;40(13–14):1955–81, 2043–8. [27] Riccio CA, Wolfe M, Davis B, et al. Attention deficit hyperactivity disorder: manifestation in adulthood. Arch Clin Neuropsychol 2005;20:249–69. [28] O’Donnell JP, McCann KK, Pluth S. Assessing adult ADHD using a self-report symptom checklist. Psychol Rep 2001;88:871–81. [29] Mick E, Faraone SV, Biederman J. Age-dependent expression of attention-deficit/hyperactivity disorder symptoms. Psychiatr Clin North Am 2004;27:215–24. [30] Mannuzza S, Klein RG, Klein DF, et al. Accuracy of adult recall of childhood attention deficit hyperactivity disorder. Am J Psychiatry 2002;159:1882–8. [31] Roy-Byrne P, Scheele L, Brinkley J, et al. Adult attention-deficit hyperactivity disorder: assessment guidelines based on clinical presentation to a specialty clinic. Compr Psychiatry 1997;38(3):133–40. [32] Applegate B, Lahey BB, Hart EL, et al. Validity of the age-of-onset criterion for ADHD: a report from the DSM-IV field trials. J Am Acad Child Adolesc Psychiatry 1997;36(9): 1211–21. [33] Barkley RA, Biederman J. Toward a broader definition of the age-of-onset criterion for attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 1997;36(9): 1204–11. [34] Wender PH, Wolfe LE, Wasserstein J. Adults with ADHD: an overview. Ann N Y Acad Sci 2001;931:1–16. [35] Ward MF, Wender PH, Reimherr FW. The Wender Utah Rating Scale: an aid in the retrospective diagnosis of childhood attention deficit hyperactivity disorder. Am J Psychiatry 1993;150:885–90. [36] Wilens TE, Kwon A, Tanguay S, et al. Characteristics of adults with attention deficit hyperactivity disorder plus substance use disorder: the role of psychiatric comorbidity. Am J Addict 2005;14:319–27. [37] Elliott H. Attention-deficit/hyperactivity disorder in adults: a guide for the primary care physician. South Med J 2002;95(7):736–42. [38] Weiss MD, Weiss JR. A guide to the treatment of adults with ADHD. J Clin Psychiatry 2004;65(Suppl 3):27–37. [39] Adler L, Cohen J. Diagnosis and evaluation of adults with attention-deficit/hyperactivity disorder. Psychiatr Clin North Am 2004;27:187–201. [40] Asherson P. Clinical assessment and treatment of attention deficit hyperactivity disorder in adults. Expert Rev Neurother 2005;5(4):525–39. [41] Downey KK, Stelson FW, Pomerleau O, et al. Adult attention deficit hyperactivity disorder: psychological test profiles in a clinical population. J Nerv Ment Dis 1997;185: 32–8. [42] Wilens TE, Dodson W. A clinical perspective of attention-deficit/hyperactivity disorder into adulthood. J Clin Psychiatry 2004;65:1301–13. [43] Montano B. Diagnosis and treatment of ADHD adults in primary care. J Clin Psychiatry 2004;65(suppl 3):18–21. [44] Frazier TW, Youngstrom EA, Glutting JJ, et al. ADHD and achievement: meta-analysis of the child, adolescent and adult literatures and a concomitant study with college students. J Learn Disabil 2007;40:49–65. [45] Biederman J, Faraone SV, Spencer TJ, et al. Functional impairments in adults with selfreports of diagnosed ADHD: a controlled study of 1001 adults in the community. J Clin Psychiatry 2006;67:524–40.

470

MOSS

et al

[46] Heiligenstein E, Guenther G, Levy A, et al. Psychological and academic functioning in college students with attention deficit hyperactivity disorder. J Am Coll Health 1999;47(4): 181–5. [47] Shaw-Zirt B, Popali-Lehane L, Chaplin W, et al. Adjustment, social skills, and self-esteem in college students with symptoms of ADHD. J Atten Disord 2005;8(3):109–20. [48] Wender PH. Attention-deficit hyperactivity disorder in adults. Psychiatr Clin North Am 1998;21:761–74. [49] Secnik K, Swensen A, Lage MJ. Comorbidities and costs of adult patients diagnosed with attention-deficit hyperactivity disorder. Pharmacoeconomics 2005;23(1):93–102. [50] Centers for Disease Control. Morbidity and mortality weekly report [monograph on the Internet].Washington: Centers for Disease Control; 2005 Sept. Available from: http://www. cdc.gov/MMWR/preview/mmwrhtml/mm5434a1.htm. Accessed March 9, 2007. [51] Biederman J, Faraone SV, Monuteaux MC. Differential effect of environmental adversity by gender: Rutters’ index of adversity in a group of boys and girls with and without ADHD. Am J Psyhiatry 2002;158:1556–62. [52] Harpin VA. The effect of ADHD on the life of an individual, their family, and community from preschool to adult life. Arch Dis Child 2005;90(Suppl 1):i2–7. [53] Biederman J, Faraone SV, Spencer T, et al. Patterns of psychiatric comorbidity, cognition, and psychosocial functioning in adults with attention deficit hyperactivity disorder. Am J Psychiatry 1993;150:1792–8. [54] Biederman J, Faraone SV, Spencer T, et al. Gender differences in a sample of adults with attention deficit hyperactivity disorder. Psychiatry Res 1994;53:13–29. [55] Eakin L, Minde K, Hechtman L, et al. The marital and family functioning of adults with ADHD and their spouses. J Atten Disord 2004;8(1):1–10. [56] Barkley RA, Guevremont DC, Anastopoulos AD, et al. Driving-related risks and outcomes of attention deficit hyperactivity disorder in adolescents and young adults: a 3- to 5-year follow-up survey. Pediatrics 1993;92(2):212–8. [57] Murphy K, Barkley R. Prevalence of DSM-IV symptoms of ADHD in adult licensed drivers: implications for clinical diagnosis. J Atten Disord 1996;1:147–61. [58] Wilens TE, Biederman J, Mick E, et al. Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders. J Nerv Ment Dis 1997;185(8): 475–82. [59] Biederman J, Wilens T, Mick E, et al. Psychoactive substance use disorders in adults with attention deficit hyperactivity disorder (ADHD): effects of ADHD and psychiatric comorbidity. Am J Psychiatry 1995;152(11):1652–8. [60] Aviram RB, Rhum M, Levin FR. Psychotherapy of adults with comorbid attention-deficit/ hyperactivity disorder and psychoactive substance use disorder. J Psychother Pract Res 2001;10(3):179–86. [61] Wilens TE, Biederman J, Mick E. Does ADHD affect the course of substance abuse? Findings from a sample of adults with and without ADHD. Am J Addict 1998;7(2):156–63. [62] Leibson CL, Katusic SK, Barbaresi WJ, et al. Use and costs of medical care for children and adolescents with and without attention-deficit/hyperactivity disorder. JAMA 2001;285(1): 60–6. [63] Swensen AR, Birnbaum HG, Secnik K, et al. Attention-deficit/hyperactivity disorder: increased costs for patients and their families. J Am Acad Child Adolesc Psychiatry 2003; 42(12):1415–23. [64] Murphy P, Schachar R. Use of self-ratings in the assessment of symptoms of attention deficit hyperactivity disorder in adults. Am J Psychiatry 2000;157:1156–9. [65] Gallagher R, Blader J. The diagnosis and neuropsychological assessment of adult attention deficit/hyperactivity disorder: scientific and practical guidelines. Ann N Y Acad Sci 2001; 931:148–71. [66] Wasserstein J. Diagnostic issues for adolescents and adults with ADHD. J Clin Psychol 2005;61:535–47.

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[67] Zucker M, Morris MK, Ingram SM, et al. Concordance of self- and informant ratings of adults’ current and childhood attention-deficit/hyperactivity disorder symptoms. Psychol Assess 2002;14(4):379–89. [68] McCann BS, Roy-Byrne P. Screening and diagnostic utility of self-report attention deficit hyperactivity disorder scales in adults. Compr Psychiatry 2004;45(3):175–83. [69] Kessler RC, Adler L, Ames M, et al. The World Health Organization adult ADHD selfreport scale (ASRS): a short screening scale for use in the general population. Psychol Med 2005;35:245–56. [70] Adler L, Spencer T, Faraone SV, et al. Validity of pilot Adult ADHD Self-Report Scale (ASRS) to rate adult ADHD symptoms. Ann Clin Psychiatry 2006;18(3):145–8. [71] McCann BS, Scheele L, Ward N, et al. Discriminant validity of the Wender Utah Rating Scale for attention-deficit/hyperactivity disorder in adults. J Neuropsychiatry Clin Neurosci 2000;12:240–5. [72] Mehringer AM, Downey KK, Schuh LM, et al. The assessment of hyperactivity and attention: development and preliminary validation of a brief self-assessment of adult ADHD. J Atten Disord 2002;5(4):223–31. [73] Schoechlin C, Engel RR. Neuropsychological performance in adult attention-deficit hyperactivity disorder: meta-analysis of empirical data. Arch Clin Neuropsychol 2005;20:727–44. [74] Hervey AS, Epstein JN, Curry JF. Neuropsychology of adults with attention-deficit/hyperactivity disorder: a meta-analytic review. Neuropsychology 2004;18:485–503. [75] Seidman LJ, Doyle A, Fried R, et al. Neuropsycholgoical function in adults with attentiondeficit/hyperactivity disorder. Psychiatr Clin North Am 2004;27:261–82. [76] Seidman LJ. Neuropsychological functioning in people with ADHD across the lifespan. Clin Psychol Rev 2006;26:466–85. [77] Mackin RS, Horner MD. Relationship of the Wender Utah Rating Scale to objective measures of attention. Compr Psychiatry 2005;46:468–71. [78] Fargason RE, Ford CV. Attention deficit hyperactivity disorder in adults: diagnosis, treatment, and prognosis. South Med J 1994;87(3):302–10. [79] Naseem S, Chaudhary B, Collop N. Attention deficit hyperactivity disorder in adults and obstructive sleep apnea. Chest 2001;119(1):294–6. [80] Rostain AL, Ramsay JR. A combined treatment approach for adults with ADHDdresults of an open study of 43 patients. J Atten Disord 2006;10(2):150–9. [81] McGough JJ, Smalley SL, McCracken JT, et al. Psychiatric comorbidity in adult attention deficit hyperactivity disorder: findings from multiplex families. Am J Psychiatry 2005;162: 1261–7. [82] Shekim WO, Asarnow RF, Hess E, et al. A clinical and demographic profile of a sample of adults with attention deficit hyperactivity disorder, residual state. Compr Psychiatry 1990; 31(5):416–25. [83] Wilens TE, McDermott SP, Biederman J, et al. Cognitive therapy in the treatment of adults with ADHD: a systematic chart review of 26 cases. J Cogn Psychother 1999;13(3):215–26. [84] Torgerson T, Gjervan B, Rasmussen K. ADHD in adults: a study of clinical characteristics, impairment and comorbidity. Nord J Psychiatry 2006;60:38–43. [85] Searight HR, Burke JM. Adult attention deficit hyperactivity disorder. Waltham, MA: UpToDate; 2006. Available at: http://www.utdol.com/utd/content/topic.do?topicKey¼ psychiat/8007&selectedTitle¼2w1758&source¼search_result. Accessed May 9, 2006. [86] MTA Cooperative Group. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 1999;56(12): 1073–86. [87] Brown RT, Amler RW, Freeman WS, et al. American Academy of Pediatrics Committee on Quality Improvement; American Academy of Pediatrics Subcommittee on AttentionDeficit/Hyperactivity Disorder. Pediatrics 2005;115(6):e749–57. [88] Lutton ME, Leach L, Triezenberg D. Clinical inquiries. Does stimulant therapy help adult ADHD? J Fam Pract 2003;52(11):888–9, 892.

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MOSS

et al

[89] Greenhill LL, Pliszka S, Dulcan MK, et al. American Academy of Child and Adolescent Psychiatry. Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults. J Am Acad Child Adolesc Psychiatry 2001;41(2 Suppl): 26S–49S. [90] Wolraich ML, Wibbelsman CJ, Brown TE, et al. Attention-deficit/hyperactivity disorder among adolescents: a review of the diagnosis, treatment, and clinical implications. Pediatrics 2005;115(6):1734–46. [91] Nutt DJ, Fone K, Asherson P, et al. Evidence-based guidelines for management of attention-deficit/hyperactivity disorder in adolescents in transition to adult services and in adults: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2007;21(1):10–41. [92] Stockl KM, Hughes TE, Jarrar MA, et al. Physician perceptions of the use of medications for attention deficit hyperactivity disorder. J Manag Care Pharm 2003;9(5):416–23. [93] Food and Drug Administration. Alert for healthcare professionals: pemoline tablets and chewable tablets (marketed as Cylert). Available at: www.fda.gov/cder/drug/InfoSheets/ HCP/pemolineHCP.htm. Accessed March 10, 2007. [94] Mattes JA, Boswell L, Oliver H. Methylphenidate effects on symptoms of attention deficit disorder in adults. Arch Gen Psychiatry 1984;41(11):1059–63. [95] Wender PH, Reimherr FW, Wood D, et al. A controlled study of methylphenidate in the treatment of attention deficit disorder, residual type, in adults. Am J Psychiatry 1985; 142(5):547–52. [96] Spencer T, Biederman J, Wilens T, et al. Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 2001;58(8): 775–82. [97] Spencer T, Biederman J, Wilens T, et al. A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder. Biol Psychiatry 2005;57(5):456–63. [98] Weisler RH, Biederman J, Spencer TJ, et al. Mixed amphetamine salts extended-release in the treatment of adult ADHD: a randomized, controlled trial. CNS Spectr 2006;11(8): 625–39. [99] Wilens TE, Faraone SV, Biederman J, et al. Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics 2003;111(1):179–85. [100] Cox DJ, Merkel RL, Moore M, et al. Relative benefits of stimulant therapy with OROS methylphenidate versus mixed amphetamine salts extended release in improving the driving performance of adolescent drivers with attention-deficit/hyperactivity disorder. Pediatrics 2006;118(3):e704–10. [101] Michelson D, Adler L, Spencer T, et al. Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies. Biol Psychiatry 2003;53(2):112–20. [102] Van Brunt DL, Johnston JA, Ye W, et al. Factors associated with initiation with atomoxetine versus stimulants in the treatment of adults with ADHD: retrospective analysis of administrative claims data. J Manag Care Pharm 2006;12(3):230–8. [103] Wilens TE, Biederman J, Prince J, et al. Six-week, double-blind, placebo-controlled study of desipramine for adult attention deficit hyperactivity disorder. Am J Psychiatry 1996; 153(9):1147–53. [104] Wilens TE, Prince JB, Spencer T, et al. An open trial of bupropion for the treatment of adults with attention-deficit/hyperactivity disorder and bipolar disorder. Biol Psychiatry 2003;54(1):9–16. [105] Wilens TE, Prince JB, Spencer T, et al. A controlled clinical trial of buproprion for attention deficit hyperactivity disorder in adults. Am J Psychiatry 2001;158(2):282–8. [106] Wilens TE, Biederman J, Spencer TJ, et al. A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder. Am J Psychiatry 1999;156(12):1931–7.

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[107] Weisler RH, Biederman J, Spencer TJ, et al. Long-term cardiovascular effects of mixed amphetamine salts extended release in adults with ADHD. CNS Spectr 2005;10(12 Suppl. 20): 35–43. [108] Wilens TE, Hammerness PG, Biederman J, et al. Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry 2005;66(2):253–9. [109] Wilens TE, Zusman RM, Hammerness PG, et al. An open-label study of the tolerability of mixed amphetamine salts in adults with attention-deficit/hyperactivity disorder and treated primary essential hypertension. J Clin Psychiatry 2006;7(5):696–702. [110] Center for Drug Evaluation and Research. Food and Drug Administration. Available at: www.accessdata.fda.gov/scripts/cder/drugsatfda. Accessed March 10, 2007. [111] Gutgesell H, Atkins D, Barst R, et al. AHA Scientific Statement: cardiovascular monitoring of children and adolescents receiving psychotropic drugs. J Am Acad Child Adolesc Psychiatry 1999;38(8):1047–50. [112] Center for Drug Evaluation and Research. Public Health Advisory: Suicidal thinking in children and adolescents being treated with Strattera (atomoxetine). Food and Drug Administration. Available at: www.fda.gov/cder/drug/advisory/atomoxetine.htm. Accessed March 10, 2007. [113] Ramsay JR, Rostain AL. A cognitive therapy approach for adult attention/deficit hyperactivity disorder. J Cogn Psychother 2003;17(4):319–34. [114] Safren SA, Sprich S, Chulvick S, et al. Psychosocial treatments for adults with attentiondeficit/hyperactivity disorder. Psychiatr Clin North Am 2004;27:349–60. [115] Hesslinger B, van Elst LT, Nyberg E, et al. Psychotherapy of attention deficit hyperactivity disorder in adults: a pilot study using a structured skills training program. Eur Arch Psychiatry Clin Neurosci 2002;252:177–84. [116] Stevenson CS, Whitmont S, Bornholt L, et al. A cognitive remediation program for adults with attention deficit hyperactivity disorder. Aust N Z J Psychiatry 2002;36:610–6. [117] Silver LB. Attention deficit/hyperactivity disorder in adult life. Child Adolesc Psychiatr Clin North Am 2000;9(3):511–23. [118] Murphy K. Psychosocial treatments for ADHD in teens and adults: a practice-friendly review. J Clin Psychol 2005;61:607–19. [119] Kates N. Attention deficit disorder in adults: management in primary care. Can Fam Physician 2005;51:53–9. [120] Schubiner H, Saules KK, Arfken CL, et al. Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence. Exp Clin Psychopharmacol 2002;10(3):286–94. [121] Castaneda R, Sussman N, Levy R, et al. Treatment algorithm for attention deficit hyperactivity disorder in cocaine-dependent adults: a one-year private practice study with longacting stimulants, fluoxetine, and bupropion. Subst Abus 1999;20(1):59–71. [122] Wilens TE. Attention-deficit/hyperactivity disorder and the substance use disorders: the nature of the relationship, subtypes at risk, and treatment issues. Psychiatr Clin North Am 2004;27(2):283–301. [123] Einarson A. Abrupt discontinuation of psychotropic drugs following confirmation of pregnancy: a risky practice. J Obstet Gynaecol Can 2005;27(11):1019–22. [124] Golub M, Costa L, Crofton K, et al. NTP-CERHR Expert Panel report on the reproductive and developmental toxicity of methylphenidate. Birth Defects Res B Dev Reprod Toxicol 2005;74(4):300–81. [125] Golub M, Costa L, Crofton K, et al. NTP-CERHR Expert Panel report on the reproductive and developmental toxicity of amphetamine and methamphetamine. Birth Defects Res B Dev Reprod Toxicol 2005;74(6):471–584. [126] Briggs GG, Freman RK, Yaffe SJ. Drugs in pregnancy and lactation, 6th edition. Baltimore: Lippincott Williams & Wilkins p. 66–71, 909–10.

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Recent Advances in the Understanding and Treatment of Anxiety Disorders Steven L. Shearer, PhDa,b,* a

Residency Training Program in Family Medicine, Department of Family Medicine, Franklin Square Hospital Center, 9101 Franklin Square Drive, Suite 205, Baltimore, MD 21237, USA b Anxiety and Stress Disorders Institute of Maryland, 6525 North Charles Street, Towson, MD 21204, USA

Anxiety is ubiquitous. Everyone experiences episodic or situational anxiety symptoms. Diagnosable anxiety disorders are the most common mental health disorders, more prevalent than both affective and substance abuse disorders. In the general population, 1-year prevalence for any criterionbased anxiety disorder is 16% [1], and lifetime prevalence is 28.8% [2]. Compared with median age of onset among mood disorders (age 30), median age of onset among anxiety disorders is much younger (age 11) [2]. Anxiety disorders can adversely affect quality of life, mobility, education, employment, social functioning, health care, and physical well being. Although the directional sequence of comorbidity varies, a primary anxiety disorder often contributes to secondary depression or substance abuse. The presence of an anxiety disorder is significantly associated with thyroid disease, respiratory disease, gastrointestinal disease, arthritis, migraine headaches, and allergic conditions, and, this comorbidity with physical conditions is significantly associated with poor quality of life and disability [3]. Anxiety disorders impose a societal economic burden comparable with the cost of depression, with 54% of the cost expended for nonpsychiatric medical care of physical complaints [4]. Individuals with anxiety disorders incur twofold the primary care costs and overall health care costs compared with those without anxiety disorders, even when adjusted for medical comorbidities [5]. Among patients presenting to their primary care physician with a new complaint, point prevalence of anxiety disorders was 16.4% [6] Lifetime prevalence rates for anxiety disorders in primary care settings range from * Department of Family Medicine, Franklin Square Hospital Center, 9101 Franklin Square Drive, Suite 205, Baltimore, MD 21237. E-mail address: [email protected] 0095-4543/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pop.2007.05.002 primarycare.theclinics.com

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14% to 30% [7]. Most people suffering from anxiety disorders seek treatment in primary care settings, and, most present with generalized anxiety disorder (GAD), panic disorder, and posttraumatic stress disorder (PTSD) [7]. Although anxiety disorders are prevalent, costly, and disruptive to patients’ lives, rates of detection and of evidence-based treatment remain low in primary care settings [7]. Surveyed family physicians report that they are much more knowledgeable about effective treatments for depression (88%) compared with panic disorder (17%) and generalized anxiety disorder (13%) [8]. Nearly half of primary care patients with anxiety disorders remain untreated; however, when treated, the care received from primary care physicians and psychiatrists is similar [9]. This review summarizes the phenomenology, diagnosis, and evidencebased treatment of panic disorder, specific phobia, social anxiety disorder, generalized anxiety disorder, and obsessive–compulsive disorder (OCD). (Posttraumatic stress disorder [PTSD] is reviewed in the article by Nakell in this issue.) Given the brevity of this review, preference is given to literature from the last 4 years that has contributed to better understanding and treatment of the anxiety disorders. Panic disorder and agoraphobia Prevalence Lifetime prevalence is 22.7% for isolated panic attacks, 3.7% for panic disorder, and 1.1% for panic disorder with agoraphobia (ie, anxiety or avoidance related to situations in which escape may be difficult or in which help may not be available) [10]. Although agoraphobia especially is associated with substantial severity, impairment, and comorbidity, even isolated panic attacks are associated with meaningful role impairment [10]. Other recent data suggest higher lifetime prevalence for panic disorder (5.1%) and lower lifetime prevalence for agoraphobia (0.17%) but confirm that the presence of agoraphobia reflects a more severe variant of panic disorder [11]. Individuals with panic disorder coupled with agoraphobia were more likely to seek treatment and had earlier ages at onset and first treatment, longer episodes, and more severe disability, impairment, panic symptomatology, and Axis I and II comorbidity than those having panic disorder without agoraphobia [11]. Etiology and perpetuation Despite the obvious burst of sympathetic arousal, no specific biological dysfunction seems to underlie most panic attacks. Isolated panic attacks are common; panic disorder is much less common. Susceptibility to panic disorder is moderately heritable, but etiology is multifactorial [1], including adverse early experiences that may sensitize an individual to feelings of being overwhelmed or loss of control.

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Components of the fear-conditioning process and temperamental ‘‘anxiety sensitivity’’ (ie, fearful response to anxiety symptoms) both seem to aggregate in families. Panicky arousal and compelling symptoms that occur in the context of such preexisting vulnerabilities may initiate a vicious cycle. In short, fearful self-monitoring and efforts to control or avoid panicky arousal that is deemed dangerous only escalate panic proneness. Clinical presentation and impact In the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), panic disorder is defined by discreet episodes of marked autonomic arousal (eg, tachycardia, palpitations, sweating, trembling, shortness of breath, chest pain, dizziness) that are accompanied by catastrophic thinking (eg, fear of fainting, going crazy, losing control, dying) and are not directly caused by a substance or medical condition. Episodic, acute panic is the defining feature, but the ongoing impact of panic disorder is more a function of worry about and avoidance of anxious arousal and/or physical symptoms between panic attacks. Panic attacks can occur in any of the anxiety disorders; however, fear of panicky arousal that feels dangerous, unprovoked, and unexplained, plus the consequences of that fear, are what define panic disorder. When, in about half of cases, panic disorder includes attribution of possible panic to particular places or situations (eg, driving, crowds, flying, enclosed places), often with significant avoidance, it is designated as panic disorder with agoraphobia. The DSM-IV-TR portrays agoraphobia as a complication of panic disorder; however, recent data suggest that such a one-way causal relationship between spontaneous panic attacks and agoraphobia is incorrect [12]. Panic attacks, unlike ordinary anxiety, can feel truly life threatening. Therefore, sufferers usually first seek care in emergency or primary care settings and may be quite persistent in seeking medical consultations despite reassurance. They often are consumed by daily ‘‘what if?’’ worries related to the perceived dangerousness of panic attacks (eg, ‘‘What if I pass out while driving? What if my doctor is wrong and this is cardiac? What if I can’t sleep at all? What if this happens while I’m sitting in church?’’). If there is prominent depersonalization or derealization during panic, fear usually focuses on ‘‘going crazy’’ or ‘‘losing control.’’ A person may also experience being awakened from sound sleep by terrifying panic. Nocturnal panic attacks are non–rapid eye movement events that are distinguished from sleep terrors, sleep apnea, nightmares, or dreaminduced arousals and are not linked with differences in sleep architecture. Nocturnal panic attacks are common among patients with panic disorder, with 44% to 71% reporting at least 1 experience [13]. In a randomized, controlled trial, cognitive–behavioral treatment effectively reduced panic

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disorder severity, frequency of daytime and nocturnal panic attacks, and worry about nocturnal panic [14]. In primary care, patients typically present with unexplained symptoms or pain rather than direct complaints about panic attacks. It often is difficult to distinguish whether the presenting symptoms are a contributor to panic, a correlate of panic, or a compounding factor in the experience of panic. Various reports have suggested that panic disorder frequently contributes to noncardiac chest pain (40%), palpitations (45%), unexplained faintness (20%), irritable bowel syndrome (40%), and unexplained vertigo and dizziness (20%) [1]. Untreated panic disorder often is a chronically recurring, stress-sensitive disorder with a waxing and waning course marked by residual symptoms such as agoraphobia and somatization even during periods when panic attacks have ceased [15]. It is linked with higher medical utilization, medical comorbidity (eg, asthma, irritable bowel syndrome), poorer subjective physical and emotional health, depression, substance abuse, higher likelihood of suicide attempts, lower educational achievement, higher likelihood of unemployment and low work productivity, impaired social and marital functioning, and financial dependency that cannot be attributed to comorbid disorders [16]. Assessment Screening with the five-question Anxiety and Depression Detector’s two panic disorder questions (ie, In the past 3 months: ‘‘Did you ever have a spell or an attack when all of a sudden you felt frightened, anxious or very uneasy?’’ ‘‘Would you say that you have been bothered by ‘nerves’ or feeling anxious or on edge?’’) yields high sensitivity (.92) and modest specificity (.74) [17]. A positive screening result should prompt further questioning informed by the DSM-IV-TR criteria, a review of recent stressors, screening for affective disorders and substance abuse, and inquiry about the perceived danger in panic. There are many other instruments for assessing panic disorder and agoraphobia [18], but most are too time consuming or redundant for routine use in primary care. Assessment must include consideration of medical conditions commonly associated with anxiety or panic (eg, paroxysmal atrial tachycardia, supraventricular tachycardia, asthma, hyperthyroidism, Meniere’s). Most patients with panic disorder will not have positive findings that explain their panic attacks. However, panic disorder has been linked with a twofold increase in risk for coronary heart disease even when relevant confounding factors are controlled [19]. Treatment Both pharmacologic and nonpharmacologic treatments have an evidence base of established effectiveness for panic disorder. Limitations of these evidence bases and evidence regarding alternative treatments will be summarized in another section below.

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Selective serotonin reuptake inhibitors (SSRIs) are the drug of choice for treatment of panic disorder with no indication of differential efficacy within this class. Many placebo-controlled, randomized trials, meta-analyses and systematic reviews have reported medium to large effect sizes for SSRIs relative to placebo for periods up to 1 year [20]. Data also support comparable efficacy of the extended-release form of the serotonin/norepinephrine reuptake inhibitor (SNRI), venlafaxine, in panic disorder [21]. Although other second-generation antidepressants may also be helpful, supporting evidence is modest. Use of bupropion in panic disorder usually is discouraged because evidence supporting its use is lacking, and many patients report that it is uncomfortably activating or worsens panic attacks. Both the tricyclic antidepressants and monoamine oxidase inhibitors have shown effectiveness in panic disorder but have been relegated to second-line use. One report suggests that benzodiazepines prevail as the most common treatment for panic disorder in primary care despite treatment guidelines to the contrary [22]. However, a more recent report suggests that SSRIs/ SNRIs are most commonly used for anxiety disorders by both primary care physicians and psychiatrists and that primary care physicians are less likely than psychiatrists to prescribe benzodiazepines [9]. Benzodiazepines are considered second-line or adjunctive treatment because of failure to address frequent comorbid depression, tolerance or abuse potential, effects on driving, and possible deleterious effects on cognitive–behavioral treatment (CBT), especially with as-needed use [22]. Benzodiazepines, usually in extended-release or longer-acting forms, are sometimes administered concomitant to the first few weeks of an SSRI trial. Neither buspirone nor beta blockers have shown effectiveness for panic disorder in controlled trials [20]. Both initiating and discontinuing drug treatment of panic disorder often are complicated by side effects that can mimic or augment symptoms of panic attacks. Beginning antidepressants at half (or less) of the usual starting dose, gradual increases, and repeated reassurance usually are recommended. Because of its short half-life, paroxetine is especially prone to causing both common (eg, dizziness, nausea, lethargy, headache) and uncommon (eg, anxiety, tremor, confusion, paresthesias) discontinuation symptoms. Among SSRI-treated patients with panic disorder, 45% experienced a discontinuation syndrome, which subsided within a month in all but three patients who had been taking paroxetine for a long time. Discontinuation syndromes appeared to be fairly common even when performed with slow tapering and during clinical remission [23]. Approximately 40% of patients with panic disorder cannot tolerate or do not respond to SSRI or venlafaxine trials of adequate dose and duration. Many patients who do not respond to medication trials will respond to CBT; and, many patients who do not respond to CBT will respond to medication trials. The addition of CBT to imipramine treatment of panic disorder was associated with less severe side effects and fewer dropouts as a result of

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perceived side effects than treatment with imipramine alone [24]. It should be noted also that physician experience (ie, years since residency training) has been linked with medication response in panic disorder even in drug trials [25]. Many patients seem to benefit from the combination of medication and CBT in the short term, but combined treatment actually may be associated with worse outcome in panic disorder compared with CBT alone [26]. A recent Cochrane Database Review suggests that either combined therapy or psychotherapy alone may be chosen as first-line treatment for panic disorder with or without agoraphobia, depending on patient preference [27]. In more than 24 controlled trials, CBT has shown effectiveness for panic disorder that is at least comparable to pharmacologic treatment and may have effects of greater duration when treatment ends. True remission of panic disorder with high end-state functioning occurs in 50% to 70% of patients who receive CBT [28]. The cognitive component of CBT usually begins with patient education (eg, symptoms, autonomic nervous system, fear conditioning, generalization) and gentle challenging of the distorted assumptions and catastrophic thinking that perpetuate the vicious cycle of panic disorder. The belief that panic is dangerous must be addressed repeatedly, often with encouragement of relevant self-talk (eg, ‘‘This feels dangerous but it’s not’’). Patients need very specific reassurance, (eg, ‘‘No, you will not faint, have a heart attack, go crazy, or lose control because of panic’’). Avoidance of bodily arousal or places associated with past panic attacks is gradually reframed not as a solution but as the primary perpetuator of panic disorder. Every effort is made to encourage patients’ willingness to accept panic and, eventually, to seek panic to defuse its power over them. This process usually requires time, patience, and repetition, often over a period of months. The behavioral component of CBT emphasizes exposure to panicky arousal with the goal of gradual habituation to such cues. If there is no agoraphobia, interoceptive (ie, focused on stimuli within the body) exposure may focus on voluntary provocation of bodily symptoms associated with panic, (eg, running stairs to recreate tachycardia, hyperventilating to recreate shortness of breath, spinning to recreate dizziness, staring in the mirror to recreate depersonalization). With agoraphobia, in vivo exposure may focus on graduated exposure to places or situations associated with panic, (eg, driving, riding the subway, shopping, elevators). Many patients do not have access to specialist-delivered CBT because of financial means, insurance barriers, or geographic location. Books based on CBT principles are available for physician-assisted, self-directed treatment [29]. Web-based, self-directed CBT for panic disorder is evolving, but there are data suggesting that it may be an effective alternative [30]. Many physicians recommend aerobic exercise, relaxation exercises, diaphragmatic breathing exercises, or yoga for patients with panic disorder. Although there is a limited evidence base for judging the effectiveness of such techniques,

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their likely amelioration of bodily sensitization (ie, lowered threshold for panic and hyperreactivity to bodily sensations) suggests that they may have indirect benefits for patients with panic disorder. Panic disorder: pearls  Do not underestimate the importance of patient education, (eg, ‘‘The tachycardia and hypertension you have during panic are not dangerous and will keep you from passing out’’, ‘‘Your chest pain and shortness of breath are caused by hyperventilation but are not dangerous’’). Educate about how symptoms reflect false alarms from the autonomic nervous system, that panic feels dangerous but it’s not, and that panic is usually short circuited by the very willingness to have it rather than trying to control or avoid it.  Encourage reading and CBT, (eg, self-directed CBT [29] or referral for specialist-delivered CBT [31–34]). Emphasize that the best route to recovery is through willing acceptance and, eventually, even seeking panic.  When initiating an SSRI or SNRI for panic disorder, start low, go slow, reassure often, and, when discontinuing, taper slowly. Use benzodiazepines judiciously.

Specific phobias Prevalence Lifetime prevalence of specific phobias is 12.5% [2]. Developmentally normal, transient fears (eg, darkness, separation, intruders, water) are common among children; however, prevalence of specific phobias among children has been reported as high as 17.6% [35]. Etiology and perpetuation The etiology of specific phobias is likely multifactorial with variation across phobia types and individuals. Conditioning and genetic models have both garnered support and criticism. The fear-conditioning model depicts a specific phobia as the product of pairing an alarm of anxious arousal with a situation that has high likelihood of acquiring phobic properties. However, twin studies support a nonassociative model that postulates largely innate vulnerability to phobias based on exaggerated fear response to evolutionary, survival-relevant cues or a largely innate deficiency in adaptation to such cues [36]. Clinical presentation and impact In DSM-IV-TR, specific phobias are defined by excessive and persistent fear that is cued by presence or anticipation of a specific stimulus. Although

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the person usually recognizes that the fear is excessive or unreasonable, exposure to the stimulus almost invariably provokes immediate anxiety that may take the form of a panic attack. Contact with the phobic stimulus is endured with intense distress or it is avoided entirely. The avoidance, anxious anticipation, or distress must interfere significantly with the person’s normal routine, occupational or academic functioning, or social activities and relationships. Most people who have specific phobias do not present for treatment. Conversely, most anxiety disorders that present in primary care settings are not specific phobias. The DSM-IV-TR requires that the distress and avoidance associated with the phobic stimulus are not better accounted for by another disorder that may have different treatment implications. For example, if panic attacks occur primarily in response to catastrophic thinking about anxious arousal, panic disorder is the likely diagnosis, and a selective serotonin reuptake inhibitor or interoceptive exposure to bodily arousal is indicated. Apparent phobias may focus primarily on contamination and illness concerns or fear related to intrusive thoughts about losing control that would suggest OCD. A trauma history could be relevant to onset or perpetuation of some apparent phobias that actually reflect posttraumatic stress disorder. Typical phobic stimuli include small animals (eg, dogs, cats, snakes, spiders, bees, rats, mice); natural environment (eg, heights, water, dark, thunderstorms); situational (eg, closed spaces/confinement, flying, bridges); other (eg, choking, vomiting); and, blood-injury-injection phobia. Rather than a specific phobia, so-called ‘‘school phobia’’ in children may reflect separation anxiety, social anxiety, panic attacks, depression, attention/learning problems, bullying, or willful refusal without anxiety. Specific phobias cued by commonly encountered stimuli (eg, pets, insects) or accompanied by panic attacks may significantly affect mobility, social or employment possibilities, and quality of life. In contrast, someone with a severe snake phobia could easily arrange a lifestyle that precludes potential contact with the phobic stimulus. Dental phobia or blood-injury-injection phobia may lead to avoidance of needed health care with potentially serious consequences. Similarly, poor diabetic control has been reported among diabetics with blood-injury-injection phobia [37]. Assessment Although screening instruments and phobia-specific questionnaires are available [18], they are unlikely to be helpful in the primary care setting. If a specific phobia is suspected, the primary care physician should clarify first whether the presentation is best explained by another anxiety disorder with different treatment implications. If specific phobia seems the likely diagnosis, the physician should clarify the impact on functioning and decide

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whether graduated exposure is indicated, either by encouraging patient education and self-conducted exposure or by making a specialty referral. Treatment Medication generally is not indicated in the treatment of specific phobias and may dilute the effectiveness of behavioral treatment. Graduated exposure to the feared stimulus is first-line treatment for specific phobias. Preliminary reports suggest that the effects of such exposure treatment for specific phobias may be augmented by acute administration of d-cycloserine just before exposure [38]. However, in one report, d-cycloserine did not enhance the reduction of spider fears or the generalization of treatment of a single session of exposure-based therapy [39]. Confronting a hierarchy from less to more fear-arousing situations and, most importantly, staying in the situation until anxiety diminishes, usually leads to gradual habituation of the fear response. Recent reviews have documented the effectiveness of CBT for specific phobias in both children [40] and adults [41]. For example, 14 controlled studies of in vivo (ie, in reallife situations) exposure for specific phobias have consistently shown benefit [41]. Although in vivo exposure is the standard, exposure may be helpful whether it is based on imaginal, in vivo, or virtual reality cues and whether it is self-conducted or specialist-conducted [41–43]. Self-help approaches yield greater benefit for specific phobias than for other anxiety disorders [44,45]. Preparatory cognitive therapy may set the stage for exposure treatment by addressing distorted risk assessments, anxiety-arousing self-talk, feelings of being overwhelmed, and the demoralization that accompanies chronic avoidance. Anxiety management skills may be taught to encourage acceptance of distress, without escape or distraction, to best facilitate extinction. Recent emphasis in CBT has moved toward encouraging willingness to seek and accept anxiety rather than to control it through conscious effort or techniques. Results of both functional magnetic resonance and positron-emission tomography imaging studies suggest that exposure-based CBT modifies the dysfunctional neural circuitry that underpins specific phobias [46–49]. However, relapse after successful treatment is likely if intermittent, self-conducted exposure is abandoned. Blood-injury-injection phobia is a special case of specific phobia with different treatment implications. Contact with most phobic stimuli prompts increased arousal typified by tachycardia; however, exposure to bloodinjury-injection cues provokes the opposite. Initial hyperarousal is followed moments later by abrupt bradycardia and hypotension thought to reflect remnants of evolutionary adaptation to predator attack, (ie, no movement and staunched blood flow promote survival). If this vasovagal response is marked, syncope can result and may contribute to subsequent phobic conditioning to such cues. Exposure treatment is indicated, often beginning

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with verbal descriptions or pictures, but progressing to direct exposure to the relevant cues (eg, donating blood). The vasovagal response requires special adaptation. Patients are instructed to increase muscle tension or to stimulate memories of angry feelings to counter bradycardia and hypotension during exposure [50]. Specific phobias: pearls  Most individuals with specific phobias do not present for treatment. Most individuals who present with ‘‘phobias’’ do not have specific phobias. Consider whether the presented fears are best explained by a diagnosis of panic disorder with agoraphobia, OCD, or PTSD.  Graduated exposure, whether self/parent conducted [51] or specialist conducted, is likely to be helpful if it is repetitive and sustained long enough for anxiety to diminish before the exposure is terminated.  Blood-injury-injection phobia is uniquely characterized by bradycardia and hypotension that can cause syncope. Although exposure treatment is still indicated, deliberate muscle tension or angry imagery may be necessary to prevent vasovagal syncope. Social anxiety disorder (Social phobia) Prevalence Conservative estimates suggest that lifetime prevalence of social anxiety disorder is 5% [52]. Primary care data suggest similar lifetime prevalence (5.7%) [53]. Compared with patients with other psychiatric disorders in primary care, social anxiety disorder was characterized by greater functional impairment, fewer visits, and tenfold the number of concomitant substance abuse disorders [53]. Etiology and perpetuation As with panic disorder, the vulnerability for anxious apprehension, caused by hypersensitive fear circuits in the brain or adverse developmental experiences, seems to be fundamental to the etiology of social anxiety disorder. Both shyness and behavioral inhibition (ie, wariness in response to novelty) are moderately heritable and associated with subsequent development of social anxiety disorder [1]. Understanding of the neurobiology of social anxiety disorder is evolving [54]. Most of us experience memorable embarrassment without becoming consumed by the possibility of recurrence. If embarrassment is accompanied by panic, shame, repetitive replays in memory, and preexisting propensities for performance anxiety and worry-proneness, social anxiety disorder is the likely result. More than one third of social anxiety disorder sufferers report posttraumaticlike reexperiencing of socially stressful events with

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accompanying hyperarousal and avoidance [55]. Social anxiety becomes self-perpetuating, because self-absorption and self-monitoring impede social performance, creating a vicious cycle, and subsequent avoidance preempts exposure that would facilitate habituation and disprove distorted assumptions. Clinical presentation and impact Social anxiety disorder has evolved as the preferred term in the literature, but the DSM-IV-TR still uses the term social phobia. The diagnosis is defined by persistent fear of social or performance situations that involve possible scrutiny and disapproval by others. Exposure to a feared situation provokes marked distress, panic attacks, or preemptive avoidance. Worrying about possible bungled performance and subsequent embarrassment may be very specific (eg, public speaking, musical performance, or athletics) or may be generalized across many social situations (eg, dating, introductions, parties, speaking to authority figures, using the telephone, writing/eating in public, public restrooms). Hyperhidrosis, body dysmorphic disorder, or paruresis may complicate social anxiety disorder. Comorbidity between social anxiety disorder and other anxiety disorders, substance abuse disorders, and affective disorders is common. The high prevalence of alcohol abuse, especially in socially anxious men, has been explained by the self-medication hypothesis [1], but the interrelationship is complex [56]. Social phobics experience similar anxiety with and without alcohol, but they remember this experienced anxiety less precisely, perhaps serving as a reinforcer for the use of alcohol for the purpose of self-medication in future situations [57]. Popular press critics have disparaged social anxiety disorder as merely the medicalization of shyness and normal performance anxiety. Shyness correlates with but does not effectively predict social anxiety disorder, (ie, true social anxiety disorder does not develop in most shy individuals) [1]. True generalized social anxiety disorder is usually marked by significant avoidance, with deleterious impact on social relationships, lower academic and occupational achievement, lower quality-of-life ratings, and a rate of attempted suicide as high as 22% [58]. Social anxiety disorder is characterized by early-onset (mean, 15 years) and a disruptive, unremitting course if untreated; yet, more than 80% remain untreated [53]. A long-term, prospective, longitudinal, naturalistic treatment study found that social anxiety disorder has a chronic course and a greater adverse impact on social functioning than depressive symptoms or chronic medical illnesses [59]. Only 35% of patients with social anxiety disorder recovered after 10 years of prospective follow-up, and the postrecovery relapse rate was 34% during the 10-year follow-up [59]. In short, the evidence confirms that generalized social anxiety disorder is trivialized by popular conflation with shyness.

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Assessment Two well-studied tools appropriate for assessment or for tracking treatment of social anxiety disorder in the primary care setting are the self-administered Social Phobia and Anxiety Inventory and the physicianadministered Leibowitz Social Anxiety Scale [18]. However, for brief screening, use of only three questions identifies social anxiety disorder with 89% sensitivity and 90% specificity, (ie, ‘‘Is being embarrassed or looking stupid among your worst fears?’’ ‘‘Does fear of embarrassment cause you to avoid doing things or speaking to people?’’ ‘‘Do you avoid activities in which you are the center of attention?’’) [60]. Treatment The SSRIs and the SNRI venlafaxine are established as effective treatments for social anxiety disorder with the added advantage of treating common comorbidities [61]. A recent meta-analysis of 15 randomized, double-blind, placebo-controlled trials reported effectiveness of the SSRIs for social anxiety disorder with benefits in both social and occupational functioning [62]. Second-line treatments may include clonazepam, mirtazapine, and gabapentin [63]. The benefits of beta blockers are limited to very specific performance situations (eg, public speaking, musical/dance/athletic performance) rather than generalized social anxiety disorder [61]. As in specific phobias, preliminary evidence shows that d-cycloserine may augment exposure therapy in social anxiety disorder. In a randomized, double-blind, placebo-controlled trial, 50 mg of d-cycloserine administered 1 hour before exposure therapy sessions (ie, public speaking) resulted in greater effectiveness compared with a placebo before exposure sessions [64]. Five meta-analyses support the efficacy of cognitive behavioral therapy for social anxiety disorder, suggesting that in vivo exposure to social cues and cognitive interventions are most efficacious [65]. A subsequent, randomized, double-blind, placebo-controlled trial found that both fluoxetine and CBT were effective for social anxiety disorder, but combined treatment had no further advantage, and many patients remained symptomatic after 14 weeks of treatment [66]. In a Norwegian primary care setting, exposure therapy combined with sertraline showed deterioration at 1-year follow-up compared with exposure alone [67]. In a randomized, controlled trial, individual CBT for social anxiety disorder was superior both to intensive group CBT and to SSRIs [68]. Active ingredients in CBT for social anxiety disorder are being identified. For example, in a randomized, controlled trial, cognitive therapy showed superiority to social anxiety exposure therapy coupled with applied relaxation techniques [69]. Similarly, in a randomized, controlled trial comparing group therapy based on CBT versus exposure without explicit cognitive

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intervention, only participants who received the cognitive component continued to improve after treatment ended with data suggesting that this was mediated by changes in the estimated ‘‘social cost’’ in anxious situations [70]. Given frequent comorbidity with depression, it is noteworthy that CBT’s effect on social anxiety mediated 91% of the improvement in depression, but decreases in depression only accounted for 6% of the improvement in social anxiety [71]. Patients’ accessibility to CBT is a continuing concern. Initial data suggest that internet-delivered CBT supplemented with telephone support or exposure is effective for social anxiety disorder [72,73]. Social anxiety disorder: pearls  When patients present shyness, apparent isolation, or interpersonal discomfort, screen for social anxiety disorder by asking about fears of embarrassment and related avoidance of social activities.  Among patients with social anxiety disorder, watch for comorbid substance abuse (especially alcohol in men), depression, and other anxiety disorders.  SSRIs and venlafaxine may be useful for social anxiety disorder; however, a more conservative approach would begin with self-help CBT readings [74] and/or referral for specialist-delivered CBT [31]. Generalized anxiety disorder Prevalence Reported 1-year and lifetime prevalence of GAD is 2.1% and 4.1% [75]. In an earlier study, 1-year prevalence for GAD was 1.5%; however, 3.6% presented with at least subthreshold syndromes of GAD [76]. Such subthreshold presentations are as seriously impairing as full GAD [77] and are significantly related to elevated risk of subsequent psychopathology [78]. There is an 8% point prevalence of GAD in primary care settings, suggesting that this is the anxiety disorder most often seen by primary care physicians [79]. Etiology and perpetuation Generalized anxiety disorder seems to be the product of biological and psychological vulnerabilities similar to those described for panic disorder and social anxiety disorder. Although GAD is moderately heritable, findings suggest that it is a nonspecific tendency to develop emotional disorders that is heritable rather than GAD specifically [1]. For vulnerable individuals, worry becomes a self-perpetuating, self-reinforcing habit. Worry reduces subjective uncertainty, contributes to subjective vigilance and preparedness, usually dampens autonomic arousal, and

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fuels the belief that uncertain events and risk can be controlled [1]. Such relief, coupled with the nonoccurrence of low-probability feared events, provides salient reinforcement for the worry process. Repetitions tend to shape superstitious beliefs that worry is akin to problem solving that can somehow preempt bad things from happening. Worry functions as cognitive suppression and avoidance that becomes self-perpetuating and persistently distressing, in part, because it blocks other emotional processing [1]. Patients with GAD tend to overvalue the worry process, but their worries also distress them. Thus, they often cycle between indulging their worries, while at other times trying to suppress their worries. Recent evidence suggests that efforts to suppress intrusive thoughts are not effective and actually tend to increase distress [80]. Thus, efforts to suppress worries may sometimes serve as a short-term solution but, over time, probably contribute to the vicious cycle of worry-proneness. Clinical presentation and impact The current DSM-IV-TR characterization of GAD emphasizes excessive anxiety and worry about multiple foci of concern that occur more days than not for at least 6 months with significant disruption to daily life. In contrast to the tenth edition of the International Classification of Diseases (ICD-10), DSM-IV-TR emphasizes excessive worry and difficulty controlling worry. Accompanying symptoms include muscle tension, restlessness, irritability, difficulty concentrating, fatigue, or sleep disturbance. Because subthreshold presentations can be as impairing as full generalized anxiety disorder, the DSM-IV-TR diagnostic criteria (eg, 6-month duration, excessive worry) remain controversial [78,81]. Many patients with generalized anxiety disorder readily report, ‘‘I’ve been a worrier all my life.’’ However, in one sample, 87% of primary care patients with GAD did not present with the complaint of anxiety or worry; most had nonspecific somatic complaints (eg, insomnia, head/muscle aches, fatigue, gastrointestinal symptoms) [82]. Although there are many reports of GAD’s high comorbidity with depression, other anxiety disorders (especially panic disorder and social anxiety disorder), and substance use disorders, there is also a high proportion of pure GAD in primary care that is significantly impairing, poorly recognized, and rarely treated appropriately [82]. GAD is associated strongly with alcohol, drug, and nicotine dependence [75]. GAD is the anxiety disorder linked to the highest frequency (35.6%) of self-medication with alcohol and drugs, which, in turn, was associated with greater comorbidity and suicidality [83]. Comorbidities notwithstanding, recent data support the concept of generalized anxiety disorder as an independent disorder with significant impairment and disability [75]. Generalized anxiety disorder is associated with significant economic costs because of lost productivity and because of high use of medical resources.

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GAD is associated also with significant personal costs reflected in role and quality of life impairment comparable to major depression [84]. Impairment and effects on quality of life are comparable in both pure GAD and GAD that is comorbid with other disorders [85,86]. Assessment Pragmatic screening for generalized anxiety disorder in primary care should include queries about worry-proneness (eg, nearly daily, variable content); somatic symptoms of anxiety (eg, muscle tension, gastrointestinal distress, fatigue, restlessness); and impact on daily life (eg, insomnia, demoralization). The content of worries may indicate a different anxiety disorder such as panic disorder (ie, worry that arousal and related symptoms are dangerous), OCD (eg, fear of losing control, doubt or uncertainty, contamination or disease), or social anxiety disorder (eg, bungled performance, embarrassment). For more thorough assessment or treatment tracking, options include the revised Generalized Anxiety Disorder Questionnaire, which conforms to the DSM-IV-TR criteria, and the Penn State Worry Questionnaire (PSWQ) [18]. Because worry is a common feature of all anxiety disorders, the PSWQ is not specific to GAD but is a well-established measure of worryproneness with norms for GAD [87]. A newer, seven-item scale (GAD-7) has shown reliability, validity, and adequate sensitivity (89%) and specificity (82%) in a primary care setting [88]. Treatment The standard drug treatments for generalized anxiety disorder for many years were benzodiazepines and buspirone, both of which have established efficacy in GAD [89]. However, other reports question the deleterious effects of benzodiazepines (eg, driving, memory, sedation, tolerance, and possible dependence), possible adverse impact of as-needed use on CBT, and poor effectiveness for cognitive anxiety (ie, worry) as opposed to somatic anxiety [90]. Despite US Food and Drug Administration (FDA) approval for use with GAD, others conclude that buspirone is not well established as monotherapy and may be no more effective than placebo for most patients [90]. Because of established efficacy for generalized anxiety disorder and comorbid anxiety and affective disorders, the SSRIs, particularly escitalopram, paroxetine, and sertraline, are now considered first-line drug treatments. Venlafaxine and duloxetine are alternatives [91,92]. Other alternatives include tricyclic antidepressants (especially imipramine) [93] and possibly pregablin [94]. Despite practice guidelines established in 1998 that recommended SSRIs and venlafaxine for GAD, benzodiazepines remain the most common treatment [95]. There is no evidence that combined psychopharmacologic and psychological treatment is more effective than either treatment alone [26].

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A recent Cochrane Database Review reported that 13 studies showed the effectiveness of CBT for GAD compared with treatment as usual or waiting list control; however, when compared with supportive therapy, the efficacy of CBT was less clear [96]. A meta-analysis of studies comparing drug treatment and CBT for generalized anxiety disorder suggested no difference in efficacy but lower attrition rates for CBT [97]. A recent controlled trial of worry-based CBT showed effectiveness for GAD, with indications of continued improvement over the course of 2-year follow-up [98]. Current CBT for generalized anxiety disorder typically includes a variety of components, (eg, education about worry, self-recording of worries, relaxation training, exposure to worries paired with coping strategies, designated worry periods, focus on mindful attention to present experience, worries as ‘‘just thinking’’ rather than valid risk assessment and management, and challenging the worrier’s intolerance for uncertainty and rationalization of worry as adaptive safety-seeking) [99]. Historically, relaxation training has been the hallmark of treatment for GAD, but there is no evidence that physiological activation actually decreases even when patients report benefit from this treatment [100]. Alternatively, recent interest has focused on the integration of mindfulness meditation with CBT for GAD to reframe worried thought content, to encourage a present-moment mindset that is contrary to worrying, and to offer an alternative to ineffective suppression. Initial findings suggest effectiveness of this approach for GAD [101]. Similarly, initial data support ‘‘metacognitive’’ approaches for GAD that address patients’ reactivity to and efforts to control their own worried thoughts [102]. Other reports suggest that CBT for GAD also has significant impact on insomnia [103] and comorbid conditions [104] even if they are not specifically targeted. Generalized anxiety disorder: pearls  The SSRIs, particularly escitalopram, paroxetine, and sertraline, and the SNRI venlafaxine, are now considered first-line treatments for both the cognitive and somatic manifestations of GAD. As with panic disorder, it is prudent to start at half the usual starting dose.  CBT for GAD is at least as effective as drug treatment but seems to be associated with less attrition from treatment and more durable effects over time. Both drug treatment and CBT are helpful for insomnia and conditions commonly comorbid with GAD.  Worry management skills [105] and mindfulness meditation [106] encourage greater tolerance for uncertainty, an alternative to ineffective suppression, a focus on the present moment rather than future-oriented worrying, and devaluation of the worry process as ‘‘just thinking’’ rather than effective risk management. Although some patients will benefit from physician-directed self-help, specialist-delivered treatment for GAD may be necessary [31].

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Obsessive-compulsive disorder Prevalence The prevalence of OCD is not well established, but lifetime prevalence in the general population usually is estimated at 2% [107]. Other data suggest lifetime prevalence as high as 3.5% for OCD and 8.7% for obsessivecompulsive symptoms short of criterion-based diagnosis [108]. A large scale study of a Kaiser Permanente database suggested 1-year OCD prevalence of 0.84% with higher prevalence among women than men but higher prevalence among boys than girls [109]. The heterogeneity of OCD and continuing controversy about diagnostic boundaries have complicated understanding of prevalence. Etiology and perpetuation Obsessive–compulsive disorder aggregates in families with reported fourfold greater lifetime prevalence among primary relatives compared with controls [110]. Twin studies suggest that obsessive–compulsive symptoms in children are heritable, with genetic influences ranging from 45% to 65% [111]. Vulnerability to OCD seems to be greater when personal or family history is marked by excessive responsibility taking, rigid codes of conduct, equation of thought and action, perfectionism, cognitive inflexibility, or black-and-white perception that tends to be intolerant of uncertainty and ambiguity [1]. Many findings suggest that OCD is underpinned by the prefrontal cortex–basal ganglia–thalamic circuitry and the serotonergic and dopaminergic systems [107]. There are many reports of distinctive imaging studies, deranged neurocircuitry, and abnormal sertononin and dopamine activity in OCD; however, effective treatment seems to correct such changes in many patients whether the treatment is biological or behavioral. Because OCD can first appear in children after a group A beta-hemolytic streptococcal infection, there has been much interest in possible immune triggers in the onset or worsening of OCD [112]. The validity of pediatric autoimmune neuropsychiatric disorders and the significance of streptococcal infections in later onset and recurrent OCD both remain to be clarified. During periods of stress, an individual who is genetically vulnerable to OCD may experience compelling intrusive thoughts (eg, possible loss of control, possible human immunodeficiency virus [HIV] contamination) that are hard to dismiss. When alarmed by these intrusions, the individual is very likely to increase efforts to neutralize such thoughts or to seek reassurance repetitively, both of which, over time, worsen anxiety and make the intrusions more salient. A cycle of escalating intrusions, hypervigilance, futile control of inherently uncontrollable thoughts, reactive panic, and powerfully reinforcing relief through neutralizing rituals becomes self-perpetuating [1].

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Clinical presentation and impact The DSM-IV-TR defines OCD as the presence of either (1) obsessions: anxiety-arousing thoughts or images (eg, ‘‘What if I unwittingly harm my child with this bleach?’’ ‘‘What if I carelessly left appliances on that could start a fire?’’ ‘‘How can I be certain that this is not impending insanity?’’) that are experienced as remarkably intrusive and inappropriate, or (2) compulsions: anxiety-relieving, repetitive behaviors (eg, hand washing, checking, reassurance seeking) or mental acts (eg, praying, covert words or images, counting) that aim to neutralize distress or ‘‘prevent’’ bad outcomes. Obsessional thoughts are much more compelling than worries about real-life problems, such as those noted in GAD. OCD is a remarkably heterogeneous disorder across individuals, within individuals, and across time. There are both common (eg, safety checking) and uncommon (eg, ‘‘What if I run outside naked?’’) presentations across a spectrum of insight from known irrationality to quasi-delusion. Obsessive-compulsive disorder usually has gradual onset during childhood or adolescence and, without treatment, remains persistently disruptive. High health care use and low productivity are primary economic costs; diminished quality of life, functional impairment, and disruption of relationships are primary personal costs [107]. OCD has also been linked to other sources of diminished physical well being. For example, 35% of OCD patients had irritable bowel syndrome compared with only 2.5% of matched controls [113]. The similar DSM-IV-TR terms, obsessive–compulsive disorder on Axis I and obsessive–compulsive personality disorder on Axis II, have confused many physicians. Obsessive–compulsive personality disorder (OCPD) is not marked by the usually distressing obsessions and compulsions of OCD; rather, OCPD is characterized by orderliness, control, rigidity, and perfectionism that the individual sees as virtues even at the cost of flexibility, efficiency, and relationships. Although OCD and OCPD are linked, a systematic review reported that neither is a necessary or sufficient component of the other; indeed, 75% of those with OCD do not have OCPD, and 80% of those with OCPD do not have OCD [114]. Despite some overlap, popular terms for impulse-control disorders like compulsive shopping and compulsive gambling must be distinguished from the anxiety-relieving compulsions of OCD. The relationship between impulsivity and compulsivity is complex, but there are important differences such that treatment is usually dissimilar [115]. Overlap between OCD and apparently related disorders, such as hoarding, trichotillomania, skin picking, Tourette’s syndrome, body dysmorphic disorder, and hypochondriasis, is frequently observed but poorly understood. For example, unlike the DSM-IV-TR, some contend that hypochondriasis is a variant of OCD, whereas others report that, despite overlap, OCD and hypochondriasis are separable and valid diagnoses [116]. Although hoarding can function as an anxiety-relieving compulsion in OCD, hoarding

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in the absence of other OCD symptoms is marked by significantly less distress and poorer response to treatment and seems to be a clinically distinct syndrome [117]. Because OCD overlaps with so many other similar disorders, some have proposed an obsessive–compulsive spectrum of disorders, but this remains controversial [118]. The question remains whether OCD will be removed from the anxiety disorders section of DSM-V in favor of a new grouping of spectrum disorders with obsessive–compulsive features [119]. In addition to such overlapping disorders, OCD is frequently comorbid with other psychiatric disorders. In one large sample of children and adults, three of four with OCD had comorbid psychiatric disorders [109]. Depression, bipolar disorder, and other anxiety disorders are the most commonly reported comorbidities. Sex differences also have been reported: Mood disorders, anxiety disorders, eating disorders, and skin picking were more prevalent in women or girls with OCD, whereas tics, Tourette’s syndrome, and alcohol dependence were more prevalent in men or boys with OCD [120]. Although postpartum depression has been well publicized, postpartum-onset OCD is also common. In one sample, the incidence of postpartum OCD was 4% 6 weeks postnatally [121]. Given the helplessness of a newborn, the most reprehensible and frightening obsession for a new mother is that she might unwittingly harm her infant. Such obsessions are common in new mothers and, in the absence of a history of aggressive, impulsive, or psychotic behavior, can be ameliorated by appropriate education and reassurance [122]. Assessment Obsessive–compulsive disorder should be considered when patients present unrelenting reassurance seeking, frightening intrusive thoughts, persistent and marked concern about HIV/cancer/contamination, or repetitive behaviors, including repetitive avoidance. The standard assessment instrument for OCD is the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) [18]. A physician-administered form is available online [123]. Treatment First-line pharmacotherapy for OCD consists of those drugs with potent serotonergic actions (ie, SSRIs and, secondarily because of side effects, clomipramine) [124]. Direct comparisons with SSRIs suggest that the SNRI, venlafaxine, may be a viable alternative, but double-blind, placebo-controlled trials are lacking [125]. OCD often requires higher eventual SSRI dosing (two to four times the standard doses) and longer treatment (more than 1 to 2 years) compared with other anxiety disorders [107]. SSRIs also may be useful in some cases of other obsessive–compulsive spectrum disorders such as hypochondriasis and body dysmorphic disorder [126]. The treatment effect for OCD is usually gradual and partial, and many patients do not respond adequately to first-line treatment [127]. If OCD remains

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refractory after at least 3 months of maximal-tolerated SSRI dose administration, there is evidence to support augmentation with antipsychotic medications, especially risperidone; however, only about one third of this group responds, particularly those with comorbid tic disorders [128]. A recent Cochrane’s Database Review reports that antipsychotic augmentation can benefit refractory OCD but questions the efficacy of augmentation over the longer term and the value of medication augmentation compared with other strategies (eg, switching medication, adding psychotherapy) [129]. Some cases of very refractory and seriously impairing OCD may also respond to neurosurgical procedures, brain stimulation techniques, or electroconvulsive treatment [130]. Findings from several meta-analyses suggest that cognitive–behavioral treatment is at least as effective as medication for OCD [107]. CBT usually begins with challenging the beliefs that underpin OCD (eg, errant assumptions about safety, futile certainty seeking, thought–action fusion, compulsions momentarily relieve anxiety but only perpetuate OCD). Such cognitive work is usually preparation for eventual ‘‘exposure and response prevention’’ (ERP), (ie, creative exposure to anxiety-arousing obsessive thoughts coupled with delay or blocking of anxiety-relieving compulsions). There are reports of greater effectiveness of cognitive interventions [131] and other reports that cognitive intervention adds little to ERP [132]. One review notes that ERP is the most effective treatment currently available (ie, 50% to 60% recovered); however, when the asymptomatic criterion is used as the index of outcome, ERP and cognitive therapy have low and equivalent recovery rates (approximately 25%) [133]. There is some evidence that CBT may be helpful for obsessive–compulsive spectrum disorders such as hypochondriasis and body dysmorphic disorder [134]. Because both drug treatment alone and CBT alone are significantly effective for only about half of OCD sufferers, there has been much interest in combined treatments but little indication that combined treatment is superior [135]. One recent trial comparing both treatments and their combination reported that CBT had a more specific anti-obsessional effect than medication, but CBT plus medication showed the greatest improvement in mood [136]. In contrast, another study reported that at 5-year follow-up, both individual and combined treatments were equally effective [137]. Given the limited availability of OCD specialists in many communities, self-help efforts with limited professional direction may also be helpful as initial intervention in stepped care [138]. Increasing OCD sufferers’ willingness to seek anxiety-arousing obsessions [139] and addressing the overly accommodating or overly antagonistic responses of family members [140] may be integral to supporting self-help efforts. Obsessive-compulsive disorder: pearls  Contrary to common stereotypes of cleaning and checking, OCD is characterized by much more variability in presentation and phenomenology.

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Consider OCD when patients present unrelenting reassurance seeking, frightening intrusive thoughts, persistent and marked concern about HIV/cancer/germs/toxins, or repetitive behaviors, including repetitive avoidance.  The SSRIs are first-line drug treatment for OCD. Clomipramine and venlafaxine may be alternatives. Compared with SSRI indications for other disorders, drug treatment for OCD will likely require higher doses, longer duration of treatment, and multiple drug trials; yet, only about half of treated patients will improve significantly.  Cognitive–behavioral treatment that encourages willing exposure to anxiety-arousing obsessions and willing disruption of anxiety-relieving compulsions is at least as effective as drug treatment for OCD. Physicians may direct OCD sufferers to appropriate self-help resources [141] or specialist referrals [31,34] consistent with the CBT approach. Caution about evidence-based treatments Psychopharmacologic agents and cognitive–behavioral interventions have earned the status of evidence-based treatments for anxiety disorders. However, a few cautionary notes are indicated. Regarding drug trials, the placebo response rate for anxiety disorders regularly exceeds 30%; yet, a minority of antidepressant trials shows statistical superiority when compared with such a high placebo response rate [142]. Hence, negative or nonsignificant trials are not rare but rarely are published given the current climate of research sponsorship. Noncompleters often are deleted such that trials for anxiety disorders may be based on as little as one third of the original sample [143]. In a climate of competitive pressure for market share among drug manufacturers, statistically significant results may have more modest clinical significance. For example, duloxetine recently received an FDA-approved indication for generalized anxiety disorder [144]. Patients assigned randomly to either 60 mg or 120 mg once daily experienced an average 46% improvement in anxiety symptoms compared with 32% for those who took placebo. Psychic anxiety symptoms improved significantly compared with placebo, but somatic anxiety failed to separate from placebo. As has been true with other agents, there was both a modest treatment effect and a significant placebo effect. Although the measured drug response of some individuals is robust, grouped data suggest that an impressive evidence base should be tempered by humility about the efficacy of current drug treatments. Direct-to-consumer advertising may lead to unrealistic expectations about remission rates, recovery, and the burden of adverse effects associated with drug treatment. Participants for drug and CBT studies are so carefully screened that they are not typical of the real-world comorbidities familiar to primary care physicians [143]. Treatment in outcome studies is brief, usually without

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long-term follow-up; yet, anxiety disorders typically are chronic or recurrent disorders that are stress sensitive and have a fluctuating course. In one large meta-analysis, 36% of those who completed evidence-based treatment reentered treatment within 18 months [143]. Successful treatment of anxiety disorders usually requires longer treatment times, recurrent treatment, and a more individualized approach than is characteristic of published trials. Cognitive–behavioral treatment is so well established primarily because it lends itself to the manualized treatment desirable for clinical trials. On rare occasions when non-CBT approaches are standardized and scrutinized, similar efficacy has been noted [145]. Fundamental questions have been raised about whether CBT’s ostensible components are, in fact, the active ingredients [146]. Specific CBT techniques, even exposure methods, are probably less important than the relationship in which they are embedded; different clinicians get different results using the same CBT techniques [1,147]. The relationship with the physician prescriber may be just as critical to patients’ tolerance of adverse effects, perseverance with medication, eventual medication response and willingness to pursue other forms of treatment [24,25]. Because many patients or rural areas have limited access to CBT-oriented treatment by an anxiety specialist, self-help efforts deserve consideration, perhaps coupled with some physician direction or telephone or online support. Such approaches have shown improved symptoms and psychological well being for panic disorder and phobias [148]. Various alternative therapies for anxiety disorders have been advocated with widely varying evidence and safety. For example, kava extract was once commonly recommended for anxiety until extended use was linked to potential liver damage [149]. A systematic review suggested best evidence of effectiveness for exercise (GAD), relaxation training (GAD, panic disorder, dental phobia, test anxiety), and bibliotherapy (specific phobias); more limited evidence supported effectiveness for acupuncture, music, autogenic training and meditation (GAD), inositol (panic disorder, OCD), and for alcohol avoidance by people with alcohol-use disorders to reduce a range of anxiety disorders [45]. More recent reports suggest antipanic effectiveness of aerobic exercise [150] and lifestyle modification [151]. A rigorous review suggested that anxiety reduction was the largest effect of ongoing massage therapy, yielding an effect size comparable to a course of psychotherapy [152]. In a national sample, 57% of individuals with panic attacks reported using alternative treatment methods, and most reported that conventional and complementary methods were similarly helpful [153].

Summary Anxiety disorders usually are chronic or recurrent disorders characterized by stress sensitivity and a fluctuating course. Both psychopharmacologic and cognitive-behavioral approaches are well established, evidence-based

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treatments for panic disorder, social anxiety disorder, generalized anxiety disorder, and OCD. Exposure-based behavioral treatment is well established as evidence-based treatment for specific phobias. Despite impressive evidence of treatment effectiveness, there are many indications that primary care patients with anxiety disorders are not well identified and treated. Among the top two reasons given by primary care patients for their not receiving both pharmacotherapy and psychotherapy was that the patient did not ‘‘believe in’’ that form of treatment for emotional problems; however, ‘‘my doctor didn’t recommend it’’ was also a highly patient-rated reason for no treatment [9]. Such data highlight the importance of effective patient education about anxiety disorders and the range of treatment options. In one review, only 25% of primary care patients with anxiety disorders received adequate medication trials, and fewer than 10% had received specialist counseling with elements of CBT [154]. Primary care physician–delivered, guided self-help [155] and specialist-delivered CBT [156] may be helpful alternatives or additions to drug treatment of anxiety disorders. Primary care physicians can make a significant impact on patients’ lives by identifying and educating about anxiety disorders, directing patients to appropriate self-help resources, choosing evidence-based drug treatment when indicated, and making referrals for specialist care.

References [1] Barlow DH. Anxiety and its disorders: the nature and treatment of anxiety and panic. 2nd edition. New York: Guilford Press; 2002. [2] Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62(6):593–602. [3] Sareen J, Jacobi F, Cox BJ, et al. Disability and poor quality of life associated with comorbid anxiety disorders and physical conditions. Arch Intern Med 2006;166(19):2109–16. [4] Greenberg PE, Sisitsky T, Kessler RC, et al. The economic burden of anxiety disorders in the 1990s. J Clin Psychiatry 1999;60:427–35. [5] Simon G, Ormel J, VonKorff M, et al. Health care costs associated with depressive and anxiety disorders in primary care. Am J Psychiatry 1995;152(3):352–7. [6] Toft T, Fink P, Oernboel E, et al. Mental disorders in primary care: prevalence and co-morbidity among disorders. Results from the Functional Illness in Primary Care (FIP) study. Psychol Med 2005;35:1175–84. [7] Demertzis KH, Craske MG. Anxiety in primary care. Curr Psychiatry Rep 2006;8:291–7. [8] Katerndahl D, Ferrer RL. Knowledge about recommended treatment and management of major depressive disorder, panic disorder, and generalized anxiety disorder among family physicians. Prim Care Companion J Clin Psychiatry 2004;6:147–51. [9] Weisberg RB, Dyck I, Culpepper L, et al. Psychiatric treatment in primary care patients with anxiety disorders: a comparison of care received from primary care providers and psychiatrists. Am J Psychiatry 2007;164:276–82. [10] Kessler RC, Chiu WT, Jin R, et al. The epidemiology of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2006; 63:415–24.

498

SHEARER

[11] Grant BF, Hasin DS, Stinson FS, et al. The epidemiology of DSM-IV panic disorder and agoraphobia in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2006;67:363–74. [12] Bienvenu OJ, Onyike CU, Stein MB, et al. Agoraphobia in adults: incidence and longitudinal relationship with panic. Br J Psychiatry 2006;188:432–8. [13] Craske MG, Tsao JC. Assessment and treatment of nocturnal panic attacks. Sleep Med Rev 2005;9:173–84. [14] Overbeek T, Schruers K. Cognitive behavioural therapy reduces nocturnal panic in people with panic disorder. Evid Based Ment Health 2006;9:13. [15] Rubio G, Lopez-Ibor JJ Jr. What can be learnt from the natural history of anxiety disorders? Eur Psychiatry 2007;22(2):80–6. [16] Pollack MH, Allgulander C, Bandelow B, et al. WCA recommendations for the long-term treatment of panic disorder. CNS Spectr 2003;8(Suppl 1):17–30. [17] Means-Christensen AJ, Sherbourne CD, Roy-Byrne PP, et al. Using five questions to screen for five common mental disorders in primary care: diagnostic accuracy of the Anxiety and Depression Detector. Gen Hosp Psychiatry 2006;28:108–18. [18] Antony MM, Orsillo SM, Roemer L. Practitioner’s guide to empirically based measures of anxiety. New York: Kluwer Academic/Plenum Publishers; 2001. [19] Gomez-Caminero A, Blumentals WA, Russo LJ, et al. Does panic disorder increase the risk of coronary heart disease? A cohort study of a national managed care database. Psychosom Med 2005;67:688–91. [20] Roy-Byrne PP, Craske MG, Stein MB. Panic disorder. Lancet 2006;368:1023–32. [21] Bradwejn J, Ahokas A, Stein DJ, et al. Venlafaxine extended-release capsules in panic disorder: flexible-dose, double-blind, placebo-controlled study. Br J Psychiatry 2005;187: 352–9. [22] Bruce SE, Vasile RG, Goisman RM, et al. Are benzodiazepines still the medication of choice for patients with panic disorder with or without agoraphobia? Am J Psychiatry 2003;160:1432–8. [23] Fava GA, Bernardi M, Tomba E, et al. Effects of gradual discontinuation of selective serotonin reuptake inhibitors in panic disorder with agoraphobia. Int J Neuropsychopharmacol 2007, in press. [24] Marcus SM, Gorman J, Shear MK, et al. A comparison of medication side effect reports by panic disorder patients with and without concomitant cognitive behavior therapy. Am J Psychiatry 2007;164:273–5. [25] Gorman JM, Martinez JM, Goetz R, et al. The effect of pharmacotherapist characteristics on treatment outcome in panic disorder. Depress Anxiety 2003;17:88–93. [26] Black DW. Efficacy of combined pharmacotherapy and psychotherapy versus monotherapy in the treatment of anxiety disorders. CNS Spectr 2006;11(10 Suppl 12):29–33. [27] Furukawa T, Watanabe N, Churchill R. Combined psychotherapy plus antidepressants for panic disorder with or without agoraphobia. Cochrane Database Syst Rev 2007;1: CD004364. [28] Rayburn NR, Otto MW. Cognitive-behavioral therapy for panic disorder: a review of treatment elements, strategies, and outcomes. CNS Spectr 2003;8:356–62. [29] Wilson R. Facing panic: self-help for people with panic attacks. Silver Spring (MD): Anxiety Disorders Association of America; 2003. [30] Carlbring P, Bohman S, Brunt S, et al. Remote treatment of panic disorder: a randomized trial of internet-based cognitive behavior therapy supplemented with telephone calls. Am J Psychiatry 2006;163:2119–25. [31] Anxiety Disorders Association of America. Available at: www.adaa.org. Accessed July 9, 2007. [32] Association for Behavioral and Cognitive Therapies. Available at: www.aabt.org. Accessed July 9, 2007.

TREATMENT OF ANXIETY DISORDERS

499

[33] National Association of Cognitive-Behavioral Therapists. Available at: www.nacbt.org. Accessed July 9, 2007. [34] Obsessive-Compulsive Foundation. Available at: www.ocfoundation.org. Accessed July 9, 2007. [35] Muris P, Merckelbach H. How serious are common childhood fears? II. The parent’s point of view. Behav Res Ther 2000;38:813–8. [36] Kendler KS, Myers J, Prescott CA. The etiology of phobias: an evaluation of the stressdiathesis model. Arch Gen Psychiatry 2002;59:242–8. [37] Mollema ED, Snoek FJ, Ader HJ, et al. Insulin-treated diabetes patients with fear of selfinjecting or fear of self-testing: psychological comorbidity and general well-being. J Psychosom Res 2001;51:665–72. [38] Ressler KJ, Rothbaum BO, Tannenbaum L, et al. Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. Arch Gen Psychiatry 2004;61:1136–44. [39] Guastella AJ, Dadds MR, Lovibond PF, et al. A randomized controlled trial of the effect of d-cycloserine on exposure therapy for spider fear. J Psychiatr Res 2006;41(6):466–71. [40] Silverman WK, Moreno J. Specific phobia. Child Adolesc Psychiatr Clin N Am 2005;14: 819–43. [41] Choy Y, Fyer AJ, Lipsitz JD. Treatment of specific phobia in adults. Clin Psychol Rev 2007;27(3):266–86. [42] Rentz TO, Powers MB, Smits JA, et al. Active-imaginal exposure: examination of a new behavioral treatment for cynophobia (dog phobia). Behav Res Ther 2003;41:1337–53. [43] Park JM, Mataix-Cols D, Marks IM, et al. Two-year follow-up after a randomised controlled trial of self- and clinician-accompanied exposure for phobia/panic disorders. Br J Psychiatry 2001;178:543–8. [44] Newman MG, Erickson T, Przeworski A, et al. Self-help and minimal-contact therapies for anxiety disorders: is human contact necessary for therapeutic efficacy? J Clin Psychol 2003; 59:251–74. [45] Jorm AF, Christensen H, Griffiths KM, et al. Effectiveness of complementary and self-help treatments for anxiety disorders. Med J Aust 2004;181:S29–46. [46] Veltman DJ, Tuinebreijer WE, Winkelman D, et al. Neurophysiological correlates of habituation during exposure in spider phobia. Psychiatry Res 2004;132:149–58. [47] Paquette V, Levesque J, Mensour B, et al. ‘‘Change the mind and you change the brain’’: effects of cognitive-behavioral therapy on the neural correlates of spider phobia. Neuroimage 2003;18:401–9. [48] Knight DC, Smith CN, Cheng DT, et al. Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning. Cogn Affect Behav Neurosci 2004;4:317–25. [49] Straube T, Mentzel HJ, Miltner WH. Neural mechanisms of automatic and direct processing of phobogenic stimuli in specific phobia. Biol Psychiatry 2006;59:162–70. [50] Ost LG, Fellenius J, Sterner U. Applied tension, exposure in vivo, and tension-only in the treatment of blood phobia. Behav Res Ther 1991;29:561–74. [51] Antony MM, Craske MG, Barlow DH. Mastering your fears and phobias: workbook. In: 2nd edition. New York: Oxford University Press; 2006. [52] Grant BF, Hasin DS, Blanco C, et al. The epidemiology of social anxiety disorder in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2005;66:1351–61. [53] Gross R, Olfson M, Gameroff MJ, et al. Social anxiety disorders in primary care. Gen Hosp Psychiatry 2005;27:161–8. [54] Matthew SJ, Ho S. Etiology and neurobiology of social anxiety disorder. J Clin Psychiatry 2006;67(Suppl 12):9–13. [55] Erwin BA, Heimberg RG, Marx BP, et al. Traumatic and socially stressful life events among persons with social anxiety disorder. J Anxiety Disord 2006;20:896–914.

500

SHEARER

[56] Morris EP, Stewart SH, Ham LS. The relationship between social anxiety disorder and alcohol use disorders: a critical review. Clin Psychol Rev 2005;25:734–60. [57] Gerlach AL, Schiller A, Wild C, et al. Effects of alcohol on the processing of social threatrelated stimuli in socially phobic women. Br J Clin Psychol 2006;45:279–95. [58] Katzelnick DJ, Kobak KA, DeLeire T, et al. Impact of generalized social anxiety disorder in managed care. Am J Psychiatry 2001;158:1999–2007. [59] Keller MB. Social anxiety disorder clinical course and outcome: review of Harvard/Brown Anxiety Research Project (HARP) findings. J Clin Psychiatry 2006;67(suppl 12):14–9. [60] Kobak KA, Schaettle SC, Greist JH, et al. Computer-administered rating scales for social anxiety in a clinical drug trial. Depress Anxiety 1998;7:97–104. [61] Davidson JR. Pharmacotherapy of social anxiety disorder: what does the evidence tell us? J Clin Psychiatry 2006;67(suppl 12):20–6. [62] Hedges DW, Brown BL, Shwalb DA, et al. The efficacy of selective serotonin reuptake inhibitors in adult social anxiety disorder: a meta-analysis of double-blind, placebocontrolled trials. J Psychopharmacol 2007;21:102–11. [63] Schneier FR. Clinical practice. Social anxiety disorder. N Engl J Med 2006;355:1029–36. [64] Hofmann SG, Meuret AE, Smits JA, et al. Augmentation of exposure therapy with D-cycloserine for social anxiety disorder. Arch Gen Psychiatry 2006;63:298–304. [65] Hambrick JP, Weeks JW, Harb GC, et al. Cognitive-behavioral therapy for social anxiety disorder: supporting evidence and future directions. CNS Spectr 2003;8:373–81. [66] Davidson JR, Foa EB, Huppert JD, et al. Fluoxetine, comprehensive cognitive behavioral therapy, and placebo in generalized social phobia. Arch Gen Psychiatry 2004;61: 1005–13. [67] Haug TT, Blomhoff S, Hellstrom K, et al. Exposure therapy and sertraline in social phobia: I-year follow-up of a randomised controlled trial. Br J Psychiatry 2003;182:312–8. [68] Mortberg E, Clark DM, Sundin O, et al. Intensive group cognitive treatment and individual cognitive therapy vs. treatment as usual in social phobia: a randomized controlled trial. Acta Psychiatr Scand 2007;115:142–54. [69] Clark DM, Ehlers A, Hackmann A, et al. Cognitive therapy versus exposure and applied relaxation in social phobia: a randomized controlled trial. J Consult Clin Psychol 2006; 74:568–78. [70] Hofmann SG. Cognitive mediation of treatment change in social phobia. J Consult Clin Psychol 2004;72:393–9. [71] Moscovitch DA, Hofmann SG, Suvak MK, et al. Mediation of changes in anxiety and depression during treatment of social phobia. J Consult Clin Psychol 2005;73:945–52. [72] Andersson G, Carlbring P, Holmstrom A, et al. Internet-based self-help with therapist feedback and in vivo group exposure for social phobia: a randomized controlled trial. J Consult Clin Psychol 2006;74:677–86. [73] Carlbring P, Gunnarsdottir M, Hedensjo L, et al. Treatment of social phobia: randomised trial of internet-delivered cognitive-behavioural therapy with telephone support. Br J Psychiatry 2007;190:123–8. [74] Hope DA, Heimberg RG, Turk CL. Managing social anxiety: a cognitive-behavioral therapy approach therapist guide (Treatments That Work). New York: Oxford University Press; 2006. [75] Grant BF, Hasin DS, Stinson FS, et al. Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder in the USA: results from the National Epidemiologic Survey on alcohol and related conditions. Psychol Med 2005;35: 1747–59. [76] Carter RM, Wittchen HU, Pfister H, et al. One-year prevalence of subthreshold and threshold DSM-IV generalized anxiety disorder in a nationally representative sample. Depress Anxiety 2001;13:78–88. [77] Kessler RC, Wittchen HU. Patterns and correlates of generalized anxiety disorder in community samples. J Clin Psychiatry 2002;63(Suppl 8):4–10.

TREATMENT OF ANXIETY DISORDERS

501

[78] Ruscio AM, Chiu WT, Roy-Byrne P. Broadening the definition of generalized anxiety disorder: effects on prevalence and associations with other disorders in the National Comorbidity Survey Replication. J Anxiety Disord 2007;21(5):662–76. [79] Wittchen HU, Hoyer J. Generalized anxiety disorder: nature and course. J Clin Psychiatry 2001;62(suppl 11):15–9. [80] Marcks BA, Woods DW. A comparison of thought suppression to an acceptance-based technique in the management of personal intrusive thoughts: a controlled evaluation Behav Res Ther 2005;43:433–45. [81] Ruscio AM, Lane M, Roy-Byrne P, et al. Should excessive worry be required for a diagnosis of generalized anxiety disorder? Results from the US National Comorbidity Survey Replication. Psychol Med 2005;35:1761–72. [82] Wittchen HU, Kessler RC, Beesdo K, et al. Generalized anxiety and depression in primary care: prevalence, recognition, and management. J Clin Psychiatry 2002;63(suppl 8):22–34. [83] Bolton J, Cox B, Clara I, et al. Use of alcohol and drugs to self-medicate anxiety disorders in a nationally representative sample. J Nerv Ment Dis 2006;194:818–25. [84] Hoffman DL, Dukes EM, Wittchen HU. Human and economic burden of generalized anxiety disorder. Depress Anxiety, in press. [85] Henning ER, Turk CL, Mennin DS, et al. Impairment and quality of life in individuals with generalized anxiety disorder. Depress Anxiety, in press. [86] Wetherell JL, Thorp SR, Patterson TL, et al. Quality of life in geriatric generalized anxiety disorder: a preliminary investigation. J Psychiatr Res 2004;38:305–12. [87] Shearer S, Gordon L. The patient with excessive worry. Am Fam Physician 2006;73: 1049–56. [88] Spitzer RL, Kroenke K, Williams JB, et al. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med 2006;166:1092–7. [89] Mitte K, Noack P, Steil R, et al. A meta-analytic review of the efficacy of drug treatment in generalized anxiety disorder. J Clin Psychopharmacol 2005;25:141–50. [90] Allgulander C, Bandelow B, Hollander E, et al. WCA recommendations for the long-term treatment of generalized anxiety disorder. CNS Spectr 2003;8(suppl 1):53–61. [91] Baldwin DS, Polkinghorn C. Evidence-based pharmacotherapy of Generalized Anxiety Disorder. Int J Neuropsychopharmacol 2005;8:293–302. [92] Rynn MA, Riddle MA, Yeung PP, et al. Efficacy and safety of extended-release venlafaxine in the treatment of generalized anxiety disorder in children and adolescents: two placebocontrolled trials. Am J Psychiatry 2007;164:290–300. [93] Kapczinski F, Lima MS, Souza JS, et al. Antidepressants for generalized anxiety disorder. Cochrane Database Syst Rev 2003;2:CD003592. [94] Montgomery SA, Tobias K, Zornberg GL, et al. Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder: a 6-week, multicenter, randomized, doubleblind, placebo-controlled comparison of pregabalin and venlafaxine. J Clin Psychiatry 2006;67:771–82. [95] Vasile RG, Bruce SE, Goisman RM, et al. Results of a naturalistic longitudinal study of benzodiazepine and SSRI use in the treatment of generalized anxiety disorder and social phobia. Depress Anxiety 2005;22:59–67. [96] Hunot V, Churchill R, Silva de Lima M, et al. Psychological therapies for generalised anxiety disorder. Cochrane Database Syst Rev 2007;1:CD001848. [97] Mitte K. Meta-analysis of cognitive-behavioral treatments for generalized anxiety disorder: a comparison with pharmacotherapy. Psychol Bull 2005;131:785–95. [98] Dugas MJ, Ladouceur R, Leger E, et al. Group cognitive-behavioral therapy for generalized anxiety disorder: treatment outcome and long-term follow-up. J Consult Clin Psychol 2003;71:821–5. [99] Borkovec TD, Newman MG, Castonguay LG. Cognitive-behavioral therapy for generalized anxiety disorder with integrations from interpersonal and experiential therapies. CNS Spectr 2003;8:382–9.

502

SHEARER

[100] Conrad A, Roth WT, Dugas MJ. Muscle relaxation therapy for anxiety disorders: it works but how? J Anxiety Disord 2007;21(3):243–64. [101] Roemer L, Orsillo SM. An open trial of an acceptance-based behavior therapy for generalized anxiety disorder. Behav Ther 2007;38:72–85. [102] Wells A, King P. Metacognitive therapy for generalized anxiety disorder: an open trial. J Behav Ther Exp Psychiatry 2006;37:206–12. [103] Belanger L, Morin CM, Langlois F, et al. Insomnia and generalized anxiety disorder: effects of cognitive behavior therapy for gad on insomnia symptoms. J Anxiety Disord 2004;18: 561–71. [104] Provencher MD, Ladouceur R, Dugas MJ. [Comorbidity in generalized anxiety disorder: prevalence and course after cognitive-behavioural therapy]. Can J Psychiatry 2006;51: 91–9 [in French]. [105] Craske MG, Barlow DH. Mastery of your anxiety and worry: workbook (Treatments That Work). In: 2nd edition. New York: Oxford University Press; 2006. [106] Kabat-Zinn J. Full Catastrophe Living. London: Piatkus Books; 2001. [107] Griest JH, Bandelow B, Hollander E, et al. WCA recommendations for the long-term treatment of obsessive-compulsive disorder in adults. CNS Spectr 2003;8(Suppl 1):7–16. [108] Angst J, Gamma A, Endrass J, et al. Obsessive-compulsive severity spectrum in the community: prevalence, comorbidity, and course. Eur Arch Psychiatry Clin Neurosci 2004;254: 156–64. [109] Fireman B, Koran LM, Leventhal JL, et al. The prevalence of clinically recognized obsessive-compulsive disorder in a large health maintenance organization. Am J Psychiatry 2001; 158:1904–10. [110] Nestadt G, Samuels J, Riddle M, et al. A family study of obsessive-compulsive disorder. Arch Gen Psychiatry 2000;57:358–63. [111] van Grootheest DS, Cath DC, Beekman AT, et al. Twin studies on obsessive-compulsive disorder: a review. Twin Res Hum Genet 2005;8:450–8. [112] Murphy TK, Sajid MW, Goodman WK. Immunology of obsessive-compulsive disorder. Psychiatr Clin North Am 2006;29:445–69. [113] Masand PS, Keuthen NJ, Gupta S, et al. Prevalence of irritable bowel syndrome in obsessive-compulsive disorder. CNS Spectr 2006;11:21–5. [114] Mancebo MC, Eisen JL, Grant JE, et al. Obsessive compulsive personality disorder and obsessive compulsive disorder: clinical characteristics, diagnostic difficulties, and treatment. Ann Clin Psychiatry 2005;17:197–204. [115] Grant JE, Potenza MN. Compulsive aspects of impulse-control disorders. Psychiatr Clin North Am 2006;29:539–51. [116] Greeven A, van Balkom AJ, van Rood YR, et al. The boundary between hypochondriasis and obsessive-compulsive disorder: a cross-sectional study from the Netherlands. J Clin Psychiatry 2006;67:1682–9. [117] Saxena S. Is compulsive hoarding a genetically and neurobiologically discrete syndrome? Implications for diagnostic classification. Am J Psychiatry 2007;164:380–4. [118] Hollander E, Kim S, Khanna S, et al. Obsessive-compulsive disorder and obsessive-compulsive spectrum disorders: diagnostic and dimensional issues. CNS Spectr 2007;12(2 Suppl. 3):5–13. [119] Bartz JA, Hollander E. Is obsessive-compulsive disorder an anxiety disorder? Prog Neuropsychopharmacol Biol Psychiatry 2006;30:338–52. [120] Samuels JF, Riddle MA, Greenberg BD, et al. The OCD collaborative genetics study: methods and sample description. Am J Med Genet B Neuropsychiatr Genet 2006;141:201–7. [121] Uguz F, Akman C, Kava N, et al. Postpartum-onset obsessive-compulsive disorder: incidence, clinical features, and related factors. J Clin Psychiatry 2007;68:132–8. [122] Baer L. Imp of the mind: exploring the silent epidemic of obsessive bad thoughts. New York: Plume; 2002.

TREATMENT OF ANXIETY DISORDERS

503

[123] Available at: http://www.cnsforum.com/streamfile.aspx?filename¼YBOCS.pdf&path¼pdf. Accessed July 9, 2007. [124] Denys D. Pharmacotherapy of obsessive-compulsive disorder and obsessive-compulsive spectrum disorders. Psychiatr Clin North Am 2006;29:553–84. [125] Dell’Osso B, Nestadt G, Allen A, et al. Serotonin-norepinephrine reuptake inhibitors in the treatment of obsessive-compulsive disorder: a critical review. J Clin Psychiatry 2006;67: 600–10. [126] Fallon BA. Pharmacotherapy of somatoform disorders. J Psychosom Res 2004;56:455–60. [127] Fineberg NA, Gale TM. Evidence-based pharmacotherapy of obsessive-compulsive disorder. Int J Neuropsychopharmacol 2005;8:107–29. [128] Bloch MH, Landeros-Weisenberger A, Kelmendi B, et al. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry 2006;11:622–32. [129] Ipser JC, Carey P, Dhansay Y, et al. Pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders. Cochrane Database Syst Rev 2006;18(4):CD005473. [130] Dell’Osso B, Altamura AC, Allen A. Brain stimulation techniques in the treatment of obsessive-compulsive disorder: current and future directions. CNS Spectr 2005;10:966–979, 983. [131] Whittal ML, Thordarson DS, McLean PD. Treatment of obsessive-compulsive disorder: cognitive behavior therapy vs. exposure and response prevention. Behav Res Ther 2005; 43:1559–76. [132] Abramowitz JS, Taylor S, McKay D. Potentials and limitations of cognitive treatments for obsessive-compulsive disorder. Cogn Behav Ther 2005;34:140–7. [133] Fisher PL, Wells A. How effective are cognitive and behavioral treatments for obsessivecompulsive disorder? A clinical significance analysis. Behav Res Ther 2005;43:1543–58. [134] Neziroglu F, Henricksen J, Yaryura-Tobias JA. Psychotherapy of obsessive-compulsive disorder and spectrum: established facts and advances, 1995–2005. Psychiatr Clin North Am 2006;29:585–604. [135] Cottraux J, Bouvard MA, Milliery M. Combining pharmacotherapy with cognitive-behavioral interventions for obsessive-compulsive disorder. Cogn Behav Ther 2005;34:185–92. [136] O’Connor KP, Aardema F, Robillard S, et al. Cognitive behaviour therapy and medication in the treatment of obsessive-compulsive disorder. Acta Psychiatr Scand 2006;113:408–19. [137] van Oppen P, van Balkom AJ, de Haan E, et al. Cognitive therapy and exposure in vivo alone and in combination with fluvoxamine in obsessive-compulsive disorder: a 5-year follow-up. J Clin Psychiatry 2005;66:1415–22. [138] Mataix-Cols D, Marks IM. Self-help with minimal therapist contact for obsessive-compulsive disorder: a review. Eur Psychiatry 2006;21:75–80. [139] Twohig MP, Hayes SC, Masuda A. Increasing willingness to experience obsessions: acceptance and commitment therapy as a treatment for obsessive-compulsive disorder. Behav Ther 2006;37:3–13. [140] Renshaw KD, Steketee G, Chambless DL. Involving family members in the treatment of OCD. Cogn Behav Ther 2005;34:164–75. [141] Grayson J. Freedom from obsessive-compulsive disorder: a personalized recovery program for living with uncertainty. New York: Jeremy P. Tarcher/Putnam; 2003. [142] Khan A, Detke M, Khan SR, et al. Placebo response and antidepressant clinical trial outcome. J Nerv Ment Dis 2003;191:211–8. [143] Westen D, Morrison K. A multidimensional meta-analysis of treatments for depression, panic, and generalized anxiety disorder: an empirical examination of the status of empirically supported therapies. J Consult Clin Psychol 2001;69:875–99. [144] Rynn M, Russell J, Erickson J, et al. Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trial. Depress Anxiety, in press.

504

SHEARER

[145] Milrod B, Leon AC, Busch F, et al. A randomized controlled clinical trial of psychoanalytic psychotherapy for panic disorder. Am J Psychiatry 2007;164:265–72. [146] Longmore RJ, Worrell M. Do we need to challenge thoughts in cognitive behavior therapy? Clin Psychol Rev 2007;27:173–87. [147] Huppert JD, Bufka LF, Barlow DH, et al. Therapists, therapist variables, and cognitive-behavioral therapy outcome in a multicenter trial for panic disorder. J Consult Clin Psychol 2001;69:747–55. [148] Barlow JH, Ellard DR, Hainesworth JM, et al. A review of self-management interventions for panic disorders, phobias and obsessive-compulsive disorders. Acta Psychiatr Scand 2005;111:272–85. [149] Pittler MH, Ernst E. Kava extract for treating anxiety. Cochrane Database Syst Rev 2004: CD003383. [150] Strohle A, Feller C, Onken M, et al. The acute antipanic activity of aerobic exercise. Am J Psychiatry 2005;162:2376–8. [151] Lambert RA, Harvey I, Poland F. A pragmatic, unblinded randomised controlled trial comparing an occupational therapy-led lifestyle approach and routine GP care for panic disorder treatment in primary care. J Affect Disord 2007;99:63–71. [152] Moyers CA, Rounds J, Hannum JW. A meta-analysis of massage therapy research. Psychol Bull 2004;130:3–18. [153] Kessler RC, Soukup J, Davis RB, et al. The use of complementary and alternative therapies to treat anxiety and depression in the United States. Am J Psychiatry 2001;158:289–94. [154] Stein MB, Sherbourne CD, Craske MG, et al. Quality of care for primary care patients with anxiety disorders. Am J Psychiatry 2004;161:2230–7. [155] van Boeijen CA, van Oppen P, van Balkom AJ. Treatment of anxiety disorders in primary care practice: a randomised controlled trial. Br J Gen Pract 2005;55:763–9. [156] Craske MG, Golinelli D, Stein MB, et al. Does the addition of cognitive behavioral therapy improve panic disorder treatment outcome relative to medication alone in the primary-care setting? Psychol Med 2005;35:1645–54.

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Navigating the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study: Practical Outcomes and Implications for Depression Treatment in Primary Care Robert A. Cain, MD* Cleveland Clinic Lerner College of Medicine, 9500 Euclid Avenue, Cleveland, OH 44195, USA

Depression is a common medical illness with enormous personal and societal impact. The lifetime prevalence of depressive illness is 15% to 20% [1]. Approximately one third of women will experience depression in their lifetimes. For perspective, that is more common than blond hair with blue eyes for women in the United States. The global public health implications are staggering. Depressive illness constitutes 4% of the worldwide disease burden [2] and affects some 121 million people worldwide [3]. The World Health Organization estimates that by 2020 unipolar depression will be second only to ischemic heart disease as a cause of illness burden worldwide, and will be the leading cause of disability in the world [3]. There is substantial comorbidity associated with depression coexisting with other serious health problems [4–6]. Similarly, the economic impact is astronomical. Recent estimates calculate a cost of at least $44 billion dollars in related direct expenses and productivity loss associated with depression in the United States [7–11]. The need for better understanding of the disease process and improved treatment is undeniable. In the primary care of adults and adolescents, treatment of depression is an often complex daily concern. The challenge is made even more daunting

* Cleveland Clinic Brunswick Family Health Center, 3724 Center Road Suite 100, Brunswick, OH 44212, USA. E-mail address: [email protected] 0095-4543/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pop.2007.05.006 primarycare.theclinics.com

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by the paucity of real-world treatment data to guide the physician through clinical decisions. Most traditional depression studies have been of the ‘‘clinical efficacy trials’’ variety, in which generally healthy (ie, few or no comorbid health problems, no substance abuse, age less than 65, no other psychiatric disorders) recruited volunteers who have depression are treated with either drug or placebo for a relatively short time. These blinded, randomized studies (often funded by the pharmaceutical industry) compare response rates of the control and treatment groups. From this, inferences must be made regarding which treatments are most appropriate for real-world primary care patients. Such information, however, does not often translate well into real-world practice, where patients often have substantial comorbidities, and where lifelong remission, rather than short-term response, is the ultimate goal of therapy. The need for practical clinical trials in psychiatry is made even more obvious as evidence-based practice becomes the standard. Such studies describe research that is focused upon answering questions that will inform those making patient care decisions [12]. These practical studies are designed to be conducted in clinical practice settings (rather than solely in specialized or academic centers), and to be replicable under best-practice clinical conditions [12]. The National Institute of Mental Health (NIMH) addressed this pressing need with the funding of three large practical clinical trials. The most ambitious of these was the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, the largest study ever conducted with depressed patients. The other trials in this NIMH series are Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) [13], and Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) [14] which focus on bipolar disorder and psychosis and Alzheimer’s disease, respectively.

Sequenced Treatment Alternatives to Relieve Depression study design STAR*D, initially funded in 1998, was a 7-year, $35 million, multicenter, prospective, sequentially randomized controlled trial of outpatients who had nonpsychotic unipolar depression. The study used randomization at multiple levels (Box 1) via the unique equipoise-stratified randomization strategy [15] to compare switching medications or medication augmentation strategies that were deemed either to be in common use or based on distinct pharmacological properties [16,17]. Equipoise randomization implies that all available randomization choices are equally favorable to the clinician. The STAR*D protocol takes this into the real world, where patients or clinicians may rank, or stratify, available options as ‘‘more ‘‘or ‘‘less’’ favorable. The resultant design, equipoise-stratified randomization, allows patients to be randomized to available treatment options based on patient preference for

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Box 1. Multiple-level randomization of depression treatment Level 1  CIT Level 2  Switch: BUP, CT, SER, VEN  Augment: BUP, BUS, CT Level 3  Switch: NOR, MIR  Augment: LI, THY Level 4  Switch: TCP, VEN + MIR Abbreviations: BUP, bupropion SR; BUS, buspirone; CIT, citalopram; CT, cognitive therapy; LI, lithium; MIR, mirtazapine; NOR, nortriptyline; SER, sertraline; TCP, tranylcypromine; THY, triiodothyronine; VEN, venlafaxine XR.

mode of therapy. In STAR*D trials, patients could opt for medication switching, augmentation, cognitive therapy, and so forth, and then were subsequently randomized to acceptable arms of the study. This mimics real-world clinical decision-making, in which the patient is an active participant in this decision process. Results obtained in this way have particular clinical relevance for this reason. Over 120 physicians were involved in the care of the enrollees, with 23 psychiatry and 18 primary care facilities used. The inclusion of substantial numbers of primary care clinicians in the study is an important consideration, because most patients who have depression are initially seen in the primary care setting [18]. Broad inclusion criteria ensured a real-world patient population (Box 2). Exclusions were limited to patients who had psychosis, bipolar disorder, substance abuse likely to need inpatient detoxification or treatment, and pregnant or lactating women. Patients who had other concurrent psychiatric diagnoses were not excluded otherwise (in fact, 61% of enrollees had one or more such diagnoses). Significant comorbid medical problems (such as complicated diabetes, coronary artery disease, hypertension, rheumatologic disorders, chronic obstructive pulmonary disease, and so forth) were not excluded unless these conditions contraindicated the use of the study’s protocol medications. It is noteworthy that there were not substantial differences in severity of illness, demographics, or comorbidities between those seen in the primary care setting and those seen in the psychiatry setting [19]. Patients were not recruited for this study, unlike the design for most efficacy trials. Only patients presenting for medical care at one of the study

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Box 2. STAR*D study overview        

4041 patients Nonpsychotic depression Few comorbidities excluded Specialty and primary care populations Equipoise-stratified randomization 12 weeks per treatment level Up to four treatment levels 1 year follow-up upon exit

Data from Trivedi MH, Stegman D, Rush AJ, et al. STAR*D clinical procedures manual. July 31, 2002. Available at: www.edc.pitt.edu/stard/public/study_ manuals.html. Accessed February 15, 2007.

clinical centers were considered for participation. Those 18 to 75 years old with a baseline score of at least 14 on the Hamilton Depression Rating Scale (HAM-D) were then eligible if antidepressant therapy was deemed safe and indicated by a clinician. The treatment protocol included recommended visits at 2, 4, 6, 9, and 12 weeks, with an optional visit at week 14 at the clinician’s discretion. Citalopram was dosed at 20 mg/day initially, and dosing guidelines called for adjustments up to 60 mg total daily dose based on response and time on each dose between adjustments. After an optimal trial, responders and remitters could enter a 12-month follow-up phase, but all responders who did not reach and sustain full remission of their symptoms were encouraged to enter the subsequent randomized level of the study. The study size was determined by statistical projections of the number of patients needed at each treatment level, in order to ensure sufficient power to discriminate between the effectiveness of the different treatment options. An initial pool of approximately 5000 patients was expected, with 4000 participants anticipated to enter the treatment phase at level 1 [20]. About half of these were expected to have insufficient response to level 1 treatment, and thus progress to subsequent levels. At all treatment levels after level 1, participants were randomized to all treatment groups and options they deemed acceptable to them via the equipoise-stratified randomization protocol. STAR*D relied on measurement-based care protocols that included a treatment manual (with protocols and procedures) [21], didactic instruction, the use of structured evaluation of symptoms and side effects at each visit, and a centralized treatment monitoring and feedback system. The clinical decision system relied on measurement of depression symptoms with the 16-item Quick Inventory of Depressive Symptomatology (QIDS), QIDS Clinician Rating (QIDS-C), and QIDS Self-Report (QIDS-SR); side effects with the Frequency and Intensity of Side Effect Rating (FISER) and Global Rating of Side Effect Burden (GRSEB); and exit scores on HAM-D scales.

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The goal of treatment was remission. This is an important consideration, because many clinical trials focus on response rather than remission as the outcome. Remission was the treatment goal because it is associated with better long-term prognosis and functionality than response (ie, reduction of O50% in baseline symptoms) [16]. The investigators defined remission as the virtual absence of symptoms, as measured by a HAM-D score less than or equal to 7, or a last-observed QIDS-SR score of less than or equal to 5. The grand scale of the study allowed investigators the rare opportunity to also meaningfully evaluate moderators of symptom remission based on demographic features (age, rare, sex, ethnicity), social features (education, employment, income, marital status, insurance coverage), and clinical features of their depression and medical disorders. All patients entering level 1 were placed on citalopram (Celexa) and dosed according to treatment protocols guided by measured outcomes. Patients were treated for up to 12 weeks (with visits at 2, 4, 6, 9, and 12 weeks) or until intolerance or remission was evident. All those who did not achieve remission, including those with significant measured response, were encouraged to enter level 2 of treatment. Those who reached remission were followed regularly for up to 12 months. The treatment algorithm is summarized in Fig. 1. In level 2, seven treatment options were available after equipoise randomization, including four medication switch options and three augmentation options. The switch options were sertraline (Zoloft), sustained-release bupropion (Wellbutrin SR), extended-release venlafaxine (Effexor XR), or cognitive therapy. Augmentation strategies included sustained-release bupropion, buspirone (Buspar), or cognitive therapy [17]. Patients were again followed for up to 12 weeks, depending on degree of improvement and tolerability of treatments. Those who received only cognitive therapy as their switch or augmentation option and did not reach remission were then randomized again LEVEL 1

Initial Treatment: citalopram

LEVEL 2

SWITCH TO: bupropion, cognitive therapy, sertraline, venlafaxine OR AUGMENT WITH: bupropion, buspirone, cognitive therapy

LEVEL 2a

(Only for those receiving cognitive therapy in Level 2) SWITCH TO: bupropion or venlafaxine (if exiting Level 2a)

LEVEL 3

SWITCH TO: mirtazapine or nortriptyline OR AUGMENT WITH: lithium or triiodothyronine

LEVEL 4

SWITCH TO: tranylcypromine or mirtazapine combined with venlafaxine Fig. 1. STAR*D treatment algorithm.

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to receive either bupropion SR or venlafaxine XR. This would ensure that no patient would enter level 3 without at least two drug failures. Patients progressing to level 3 were re-randomized to receive either a medication switch or augmentation. This was a rare look at responses by truly treatment-resistant depressed patients. Participants in the switch arm of the study received either mirtazapine (Remeron) at up to 60 mg/day or nortriptyline (Pamelor) at up to 150 mg/day. Those in the augmentation arm were given either lithium (450–900 mg/day) or triiodothyronine (T3) at 50 mcg/day. Nonremitters were then rerandomized before level 4 treatment, which consisted of the monoamine oxidase inhibitor (MAOI) tranylcypromine (Parnate), maximum 60 mg/day, or the combination of venlafaxine XR (300 mg/day maximum) with mirtazapine (45 mg/day maximum). Patients were again followed for up to 12 weeks in this level of the study. Results Outcomes from level 1 were reported in January 2006 [19]. Of the 4041 study-eligible patients, 3671 had a subsequent visit, and 2876 of those were deemed eligible for citalopram therapy. With citalopram and close follow-up over a 12-week period (an optional 14-week visit was available for those responding at 12 weeks, but who had not yet attained remission), about 30% of patients achieved the goal of remission of symptoms (32.9% as measured by QIDS-SR, 27.5% by HAM-D) [21]. Remission rates and medication dosages were similar in the primary care and psychiatry settings [19]. The mean dose of citalopram was 41.8 mg, and mean duration of treatment was 47 days. Higher rates of remission were associated with: female, Caucasian, higher education level, marriage or cohabitation, employed, insured, shorter current episode, and fewer concurrent general medical or psychiatric disorders [19]. Of particular note, 33.5% of those reaching remission in level 1 were subsequently felt to have relapsed during the follow-up period. Thus, for some 70% of patients, it appears that citalopram alone is insufficient to sustain long-term remission from depression symptoms. The demographic analysis of the STAR*D participants provides substantial insight into depression in the United States. For more than 75% of these patients, depression was recurrent, with a greater than 16-year average duration of illness. A mean of seven lifetime depressive episodes was seen. Sixty-one percent had a concurrent psychiatric diagnosis [19]. Trivedi and colleagues [19], concluded that the level 1 results ‘‘should be generalized to routine clinical practice because this is the largest ecologically valid ‘real world’ study of outpatients with non-psychotic major depressive disorder.’’ Level 2 results were published in March 2006 [22,23]. No previous study had attempted to prove the effectiveness of switching among several antidepressant options after initial unsuccessful selective serotonin reuptake

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inhibitor (SSRI) therapy. Level 2 would also attempt to determine efficacy of the common practice of medication augmentation in a controlled, randomized study. The investigators used the equipoise-stratified randomization design to assign 565 patients to the augmentation arm, and 727 patients to switch medications after an initial unsatisfactory response to citalopram therapy in level 1. Here, the somewhat unexpected results of the unique study design were revealed (Fig. 2). Because patients were allowed to choose which therapies they could be randomized to (amongst augmentation, switching, or cognitive therapy), disparate proportions entered each treatment combination. Only 21 of 1439 patients (1.5%) accepted complete randomization to any of the seven level 2 treatments. Only 25.6% (369 of 1439) allowed cognitive therapy to be included amongst acceptable treatments. Some form of drug therapy was requested by 76.3% (1098 of 1439) of patients. Because most patients chose to have their medication either augmented or switched, and few chose to do both options, it was not possible to validly compare the outcomes of augmentation strategies with switching strategies. The reasons for the patient choices were not defined by the study design. The cohort groups in the level 2 study were distinctly different in their outcomes with citalopram treatment. Patients in the switching arm of level 2 had greater intolerance and less benefit from citalopram than did the patients in the augmentation arm of the study. In the medication switch groups, approximately 25% of patients switching to any of the three study medications (bupropion-SR, sertraline, or venlafaxine-XR) achieved remission. There were no significant differences in

Results of Level 2 Equipoise Stratified Randomization 1439 patients Eligible

Patients choose acceptable Options and are Randomized

Switch Only

Augment Only

Any Drug switch or Augment

687

586

57

Any CT (Cognitive Therapy) Switch or Augment 44

Any Treatment Except CT Alone 27

Any Treatment (Full Randomization) 21

Any Treatment Except Augment

Any Treatment Except Switch

Drug Switch or CT Augment

7

7

4

Fig. 2. Results of level 2 equipoise-stratified randomization.

Drug Augment Or CT Switch Only 1

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remission rates, tolerability, or side-effect burden among these medications. A notable finding with significant clinical implication was the revelation that intolerance to one SSRI, citalopram, did not portend intolerance to another SSRI (sertraline). Whereas 56% of patients entering the switch portion of level 2 had intolerance to citalopram at one of the study doses, sertraline was as well-tolerated as the non-SSRI bupropion-SR. Because approximately 17.6% of patients given sertraline in level 2 reached remission, it can be concluded that intolerance or lack of efficacy of one SSRI does not seem to imply the same response to another SSRI [22]. In the augmentation phase, approximately 30% of patients treated with either bupropion-SR or buspirone in addition to their citalopram achieved remission. The study authors concluded that augmentation with bupropionSR was preferred because of greater reduction in measured depression symptoms from baseline and fewer overall side effects [23]. Long-term relapse rates (as defined by relapse at any time during study participation after having achieved remission) for level 2 responders (from any group) totaled an alarming 47.4%. The rate was higher for patients who improved, but did not achieve remission. Intolerance to therapy was demonstrated in 19.5% of patients in level 2. Level 3 results were published in July 2006 [24] for the switching phase and September 2006 [25] for the augmentation phase of the study. Patients could agree to augment only, switch only, or be randomized to either. A total of 142 patients entered level 3 augmentation treatment with lithium or T3; 15.9% of lithium-treated patients and 24.7% of T3 treated patients achieved remission. These rates were not felt to be significantly different [25]. The study authors slightly favored T3 treatment over lithium, primarily because of slight advantages in effectiveness and tolerability, and lack of need for blood level monitoring; however, only 56.5% of patients who received lithium augmentation actually had their lithium blood levels checked. The median lithium blood level was 0.6 meq/liter. Improved response and tolerability may have been attainable with more widely employed lithium blood level monitoring. The switch phase of level 3 treatment studied 235 patients, who were given either mirtazapine or nortriptyline. Remission rates did not differ significantly for these two medications (12.3% for mirtazapine and 19.8% for nortriptyline). There was no difference in tolerability or adverse events. There was no clear advantage to either one of these medications, and the study authors suggest there may be only limited utility to three sequential monotherapies for depression treatment [24]. A total of 13.7% of level 3 patients achieved remission. Total relapse rate for all successful level 3 therapies was 42.9%. Additionally, 25.6% of all patients experienced intolerance to their assigned therapy. Level 4 looked at additional treatment options (MAOI or combination therapy) for multiple-treatment–resistant patients. This was the first report of a randomized treatment trial with prospectively observed patients failing

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to remit with three antecedent medication trials. McGrath and colleagues [26], published their findings in September 2006. The HAM-D average score for level 4 entrants was 20, indicating moderate to severe depression, and showed only minimal improvement from their level 1 baseline score of 23.4. The comorbidity burden was high, with 64.2% of entrants having at least one general medical condition. Some 76% had at least one additional Axis I comorbid condition, and over 19% had at least four. Randomization here produced two potentially influential findings: more of the group assigned to combination therapy had already failed mirtazapine therapy in level 3, and the proportion of patients exiting level 3 because of side effects was greater in the tranylcypromine group. The study authors, however, reported there were no differences in outcomes based on level 3 intolerance. Remission rates as measured by HAM-D scores were paltry in both groups, with only 6.9% of patients in the tranylcypromine group and 13.7% of the venlafaxine-XR and mirtazapine group achieving remission. These were not statistically different. The overall remission rate was 13.0%, but 50% of these remitters subsequently relapsed. Intolerance was experienced by 34.1% of level 4 participants. Patients taking the MAOI tranylcypromine were more likely to exit the study because of side effects. Patients who had atypical symptoms did not have significantly different remission rates when treated with MAOI therapy compared with those without such features. No significant difference in remission or symptom relief was observed between treatment groups. Low remission rates suggested that switching antidepressant medication after failure to achieve remission with three previous medication trials provides only a limited chance for success. The study authors concluded that a more tolerable side effect burden and the lack of dietary interactions favor combination therapy with venlafaxine-XR and mirtazapine for highly treatment-resistant depression patients who have failed multiple other management strategies [26]. Overall remission, relapse, and intolerance rates are summarized in Table 1. Study limitations The very nature of the equipoise-stratified randomization design can lead to unexpected results. Patients have opinions, and statistical projections Table 1 Remission, intolerance and relapse rate for 4041 STAR*D enrollees by level

Level Level Level Level

1 2 3 4

Number entering treatment

Remission rate (%)

Relapse rate (%)

Intolerance experienced (%)

3671 1439 390 123

36.8 30.6 13.7 13.0

33.5 47.4 42.9 50.0

16.3 19.5 25.6 30.1

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(however prescient) may not fully account for these. The participants’ preferences were not well-anticipated by the study’s designers, and this led to disparate number assignments in level 2 treatments and beyond. For example only 21 of 1439 patients (1.5%) in level 2 agreed to randomization of all treatment choices (see Fig. 2). The study’s ability to detect small and moderate response effects was thus compromised in levels 3 and 4. For example, the initial study design anticipated that 698 participants would enter level 3. The actual number was 377. It was also assumed that 25% would choose a switch strategy, 25% would choose an augmentation strategy, and 50% would be willing to accept all possible treatments [20]. In the actual study, 127 patients (33.7%) accepted augmentation only, 221 (58.6%) chose switching strategies only, and a mere 29 (7.7%) accepted all possible treatments. Subsequent estimates of effect sizes were not applicable at the assumed Type I error rate and desired 80% power. Comparison among treatment strategies was limited by this lack of traditional randomization. Therefore, a conclusion cannot be made regarding whether switching or augmentation is superior with any acceptable degree of confidence. The study design did not account for unexpected patient preferences, and did not provide any means of delineating the reasons why patients chose the treatment options they selected. Further investigation of this is warranted to help in the design of future practical outcome trials in psychiatry (and medicine in general). The lack of placebo controls made it difficult to account for nonspecific treatment effects, which can be substantial in depression studies [27]. Adding placebo controls in level 2 and beyond was an ethical concern for the STAR*D investigators because some patients with significant improvement (responders who did not reach remission) would have been assigned to placebo only therapy in subsequent levels. The very frank possibility of adverse outcome (suicide, need for hospitalization, adverse effects on functioning, and the like) cannot be overlooked. The use of a single agent (citalopram) at level 1 limits the generalization of this portion of the study to other medications. Further study is needed with other medications following these practical clinical outcomes trial format to adopt such generalizations. The STAR*D protocols were not blinded to patients or clinicians (but interviewers and other nonclinical personnel participating in informational capacities were blinded to treatment choices). This fosters inherent participant and observer bias. Well-designed treatment protocol manuals and patient self-reports of symptoms and side effects helped to limit clinician bias. Primary outcomes were determined by measurements of the HAM-D scores, which minimize patient bias to treatment at any given intervention. The reliance on self-reports (QIDS-SR) as secondary outcome measures may be less than ideal. The longer duration of therapy (12 weeks per level) may be a primary determining factor for success rather than the mechanism of action on

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a psychopharmacological level. Allowing an extended amount of time for a medication to reach full effectiveness, with generous dosing adjustments as appropriate, is a strategy with obvious clinical implications for treating physicians. This may help explain similar remission rates in the level 2 switch phase for treatments with three different mechanisms of action. By contrast, most traditional clinical efficacy trials stop after 8 weeks of therapy. Although the STAR*D trials are far from perfect in their construct, the primary care practice world is far from a perfect world. Concessions to study design constraints were made to most closely replicate real-world outcomes and enhance patient retention through the entire study. It is this ‘‘real world’’ focus that makes STAR*D a landmark study. As Dr. Thomas R. Insel [28], Director of NIMH stated, ‘‘There has been a gulf between research and practice. This has led to the unfortunate current state where too many research studies have little immediate relevance to practice, and too little practice is based on research evidence. NIMH has developed several practical trials such as STAR*D to bridge this gap between research and practice by studying patients in real-world settings and asking questions with practical relevance.’’ Lessons learned Because much of the STAR*D study was conducted in primary care offices with patients highly representative of such settings, the results have direct clinical implications for primary care physicians. Several of these salient features deserve further attention (Box 3). STAR*D demonstrates emphatically and conclusively that meaningful practical outcomes data can be obtained in the primary care setting. Investigators conducted treatment in primary care offices for 1091 of the 2358 (37.9% of the total patients) who entered the treatment phase with citalopram in level 1 [19]. It is noteworthy that there were no significant differences in outcomes (ie, response or remission rates, dosages prescribed) in the two settings. The use of convenient, reliable self-monitoring tools for symptoms (HAM-D, QIDS-SR) and side effects (FISER) can easily be adopted into any clinician’s routine as an important facet of depressive disease management, analogous to home glucose monitoring and self-measurement of blood pressure. Additionally, many of these measurement tools can be conducted and coordinated by nonclinical personnel. The STAR*D Study team used such personnel as well as a voice-activated interactive phone recording system to conduct follow-up interviews and complete self-assessment questionnaires. The overall results suggest that it may be prudent to consider a longer course of treatment for patients initially failing to respond to a prescribed therapy. The 12- week duration (optionally extended to 14 weeks for patients showing late, incomplete response) of each STAR*D Level may have contributed to some of the surprising findings, including a relatively

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Box 3. STAR*D study highlights  Measurement-based outcomes are crucial in the management of depression. Achieving good results depends on appropriate use of measurement tools, in the same way that the sphygmomanometer is used in hypertension management, or home glucose monitoring and hemoglobin A1c determination is vital to adequate diabetes control.  Application of evidence-based care with measured outcomes and systematically applied treatment guidelines will result in improved symptom relief for the nonremitted depressed patient.  Primary care providers who apply such treatment guidelines and functional monitoring measurements can achieve results equivalent to specialty care clinicians in the treatment of depression in the outpatient setting.  A longer trial of any drug therapy for depression can yield improved response rates. The 12-week protocols in STAR*D may have helped to bolster clinical success without compromising patient safety.  Equipoise randomization applied to practical trials validates a clinical process in which patients and clinicians form a therapeutic alliance to choose rational treatment strategies.  Application of the STAR*D treatment algorithm does not invalidate the value of evidence-based psychotherapies at all levels of pharmacological intervention.  Remission, rather than response, should be the goal of antidepressant therapy.

robust response rate to sertraline (equal to the other switch options of level 2) after initial failure of another SSRI. Longer course of treatment also permitted aggressive dosing protocols for the antidepressants in the study. Selfmeasurement of side effect burden promoted the safety and utility of this practice. Conversely, lithium dosing did not exceed 900 mg per day, and blood level monitoring (with a mean level of 0.6 meq/l) was done in only 56.5% of these patients in level 3. This may have curtailed the remission rates of this augmentation strategy. Irrespective of the treatment pathway chosen, it appears clear that little additional benefit is to be garnered by switching to another medication after the failure of two consecutive monotherapies. Remission, rather than response, should be the goal of antidepressant therapy [29,30]. In this study over 70% of patients did not attain sustained

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remission with citalopram alone, and fewer than half of all patients achieved sustained remission after four treatment levels [31]. Because it is clear that patients who reach remission with their therapy have better functional outcomes than those who do not [30,32], it appears that most patients treated with an SSRI will ultimately require additional or alternate forms of treatment to reap maximum benefit from therapeutic intervention. Many patients will be treatment-resistant if we are using sustained-remission as the gold standard of therapy. STAR*D does not guide us to the most appropriate next treatment steps, because study limitations did not enable meaningful comparison of all options at each level. Because no other form of therapy except the SSRI citalopram was offered at level 1, the effectiveness of this approach as the best available starting point was not addressed. STAR*D elegantly enumerated and detailed treatment-resistant depression on a scale not previously attempted, but it will be up to further practical outcomes studies to delineate optimum treatment of these patients.

Summary The ambitious STAR*D study attempted to answer many clinicallyrelevant issues regarding the treatment of depressed outpatients. The unique study design used an equipoise-stratified randomization scheme that enhanced the real-world expediency of the treatment options studied. Because patients who had significant comorbid medical and psychiatric problems were included, and care was provided in the outpatient primary care setting as well as outpatient psychiatric centers, the findings are particularly pertinent to primary care physicians. The extensive use of measurement-based treatment protocols promotes objectivity in a realm of often subjective clinical decision-making. Although STAR*D was unable to provide specific treatment comparisons for patients at all levels of the study, it succeeded on a grand scale in defining the prevalence of treatment-resistant depression, and serves as a model for further practical clinical outcomes studies.

References [1] Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:593–602. [2] Rodgers A, Vaughan P, Prentice T, et al. The World Health Report 2002dreducing risks, promoting healthy life. Geneva (Switzerland): WHO; 2002. [3] Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990– 2020. Global Burden of Disease Study. Lancet 1997;349:1498–504. [4] Cassano P, Fava M. Depression and public health: an overview. J Psychosom Res 2003;53: 849–57. [5] Gaynes B, Burns B, Tweed D, et al. Depression and health-related quality of life. J Nerv Ment Dis 2002;190:799–806.

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[6] Katon WJ. Clinical and health services relationships between major depression, depressive symptoms, and general medical illness. Biol Psychiatry 2003;54:216–26. [7] Adler D, McLaughlin T, Rogers W, et al. Job performance deficits due to depression. Am J Psychiatry 2006;163:1569–76. [8] Wang P, Patrick A, Avorn J, et al. The costs and benefits of enhanced depression care to employers. Arch Gen Psychiatry 2006;63:1345–53. [9] Simon GE, VonKorff M, Barlow W. Health care costs of primary care patients with recognized depression. Arch Gen Psychiatry 1995;53:850–6. [10] Greenburg PE, Stiglin LE, Finkelstein SN, et al. The economic burden of depression in 1990. J Clin Psychiatry 1993;54:405–18. [11] Chisholm D. The economic costs of depression. In: Dawson A, Tylee A, editors. Depression: social and economic timebomb. London: BMJ Books; 2001. p. 10–2. [12] March J, Silva S, Compton S, et al. The case for practical clinical trials in psychiatry. Am J Psychiatry 2005;5:836–46. [13] Sachs GS, Thase GE, Otto MW, et al. Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry 2003; 53:1028–42. [14] Stroup TS, McEvoy JP, Swartz MS. The national institute of mental health clinical antipsychotic trials of intervention effectiveness (CATIE) project: schizophrenia trial design and protocol development. Schizophr Bull 2003;29:15–31. [15] Lavori PW, Rush AJ, Wisniewski SR, et al. Strengthening clinical effectiveness trials: equipoise-stratified randomization. Biol Psychiatry 2001;50:792–801. [16] Fava M, Rush AJ, Trivedi MH, et al. Background and rationale for the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Psychiatr Clin North Am 2003;26:457–94. [17] Rush AJ, Fava M, Wisniewski SR, et al. Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design. Control Clin Trials 2004;25:119–42. [18] Regier DA, Narrow WE, Rae DS, et al. The de facto US mental and addictive disorders service system: epidemiologic catchment area prospective 1-year prevalence rates of disorders and services. Arch Gen Psychiatry 1993;50:85–94. [19] Trivedi MH, Rush AJ, Wisniewski SR, et al. Outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 2006;163:28–40. [20] Trivedi MH, Stegman D, Rush AJ, et al. STAR*D clinical procedures manual. July 31, 2002. Available at: www.edc.pitt.edu/stard/public/study_manuals.html. Accessed February 15, 2007. [21] Rush AJ, Trivedi M, Wisniewski S. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006; 163(11):1905–17. [22] Rush AJ, Trivedi M, Wisniewski S, et al. Bupropion-SR, sertraline or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med 2006;354:1231–42. [23] Trivedi M, Fava M, Wisniewski S, et al. Medication augmentation after the failure of SSRIs for depression. N Engl J Med 2006;354:1243–52. [24] Fava M, Rush AJ, Wisniewski S, et al. A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report. Am J Psychiatry 2006;163:1161–72. [25] Nierenberg A, Fava M, Trivedi M, et al. A comparison of lithium and T3 augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry 2006;163:1519–30. [26] McGrath P, Stewart J, Fava M, et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry 2006;163:1531–41.

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[27] Khan A, Detke M, Khan SR, et al. Placebo response and antidepressant clinical trial outcome. J Nerv Ment Dis 2003;19:211–8. [28] Insel T. Beyond efficacy: the STAR*D trial. Am J Psychiatry 2006;163:5–7. [29] Sobocki P, Ekman M, Agren H, et al. The mission is remission: health economic consequences of achieving full remission with antidepressant treatment for depression. Int J Clin Pract 2006;60:791–8. [30] Nierenberg AA, Wright EC. Evolution of remission as the new standard in the treatment of depression. J Clin Psychiatry 1999;60(Suppl 2):7–11. [31] Nelson JC. The STAR*D study: a four-course meal that leaves us wanting more. Am J Psychiatry 2006;163:1864–6. [32] Thase ME, Haight BR, Richard N, et al. Remission rates following antidepressant therapy with bupropion-SR or selective serotonin reuptake inhibitors: a meta-analysis of original data from seven randomized clinical trials. J Clin Psychiatry 2005;66:974–81.

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Bipolar Spectrum Disorder: Differential Diagnosis and Treatment David J. Muzina, MD Cleveland Clinic Neurology Institute/Psychiatry, 9500 Euclid Avenue, P57, Cleveland, OH 44195, USA

It must be emphasized that there are many potential causes for ‘‘depression,’’ ranging from normal mood state to pathological depressions that are either secondary to some known cause (eg, grief, induction by substances or medical problems, such as hypothyroidism) or primary mood disorders (psychiatric). This article focuses on one of the primary mood disordersd bipolar affective disorder, commonly referred to as ‘‘bipolar disorder’’ (BPD), as a common cause of depressions. Of the many diagnostic challenges associated with BPD, perhaps the most significant is the need to better differentiate BPD from major depressive disorder (MDD); ie, ‘‘unipolar depression.’’ This is because the depressive episodes associated with each of these primary mood disorders most often present with identical symptomatic featuresdindeed, our current diagnostic classification system outlines criteria for the major depressive episode that do not allow for separation of unipolar from bipolar mood disorders. Current categorical diagnostic thinking forces clinicians to attempt to differentially diagnosing major depressive episodes into either a ‘‘bipolar’’ or ‘‘unipolar’’ diagnosis. In clinical reality, this ‘‘either/or’’ classification is not often easy. Categorical diagnosis, although essential for research purposes, strays far from the early unitary vision of Emil Kraepelin regarding manic-depressive insanity as a single entity with many variants, ranging from mania and hypomania to depression and mood temperaments linked by mixed states [1]. This founding view of an affective illness such as bipolar disorder existing as a ‘‘spectrum illness’’ faded with the dissection of mood disorders into either unipolar or bipolar disorder in the mid-20th century by Leonhard, Angst, Perris and others, returning to ancient Greek phenomenological distinctions between mania and melancholia [2].

E-mail address: [email protected] 0095-4543/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pop.2007.06.001 primarycare.theclinics.com

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Regardless of the methods used to define or to differentiate bipolar versus unipolar disorder, there is relative consensus that important implications regarding treatment are present. Treatment for BPD or bipolar spectrum illness generally includes a very different pharmacological approach than for unipolar major depression. Failure to correctly diagnose may lead to delays in correct treatment, or perhaps worsening of the incorrectly treated mood disorder. Perhaps as much as two thirds of all mental health services are delivered outside of the specialty mental health care sector in the United States [3]. The relative shortage of or access to psychiatrists, development of easierto-use and safer antidepressants, and education efforts sponsored by both government and industry have moved primary care physicians (PCPs) into a principal position in the diagnosis and treatment of major depression. Unfortunately, relatively less attention has been paid to the importance of learning how and why to distinguish bipolar disorders from major depressive disorder. The early identification of BPD has been problematic even within the specialty health sector. Patients who have BPD may be misdiagnosed and inappropriately treated, resulting in significant treatment failure. For example, bipolar patients placed on antidepressant monotherapy may fail to respond, or their symptoms may even worsen. In the primary care setting, patients who have BPD may represent a significant proportion of the difficult-to-treat depressed and anxious patients [4]. Education of PCPs in the appropriate recognition and diagnosis of bipolar disorder is warranted, because a bipolar diagnosis may be missed for several years or more [5]. The missed diagnosis of BPD in the depressed outpatient may contribute significantly to treatment resistance, worsening mood symptoms and dysfunction, increased rates of hospitalization, and suicide. The main objectives of this article are to: (1) review the epidemiology and diagnostic characteristics of BPD and the ‘‘bipolar spectrum’’, (2) draw attention to the need to consider BPD in the differential diagnosis of major depression in primary care; and (3) provide an overview of the treatment of BPD. Epidemiology and diagnostic characteristics of bipolar disorder Large variations in the estimated prevalence rate for BPD have been reported in the literature. The lifetime prevalence rates for BPD in the general population in the 1990s were commonly placed around the 1% mark [6], whereas more recent surveys report rates closer to 4% [7]. Prevalence rates are clearly affected by the diagnostic criteria that are used to define BPD. When the Diagnostic and Statistical Manual for Mental Disorders. 4th edition (DSM-IV) criteria for BPD are relaxed or when other criteria are used, the prevalence of BPD dramatically increases. Based on recent data from the national comorbidity survey replication study, the estimate of lifetime prevalence for the full spectrum of bipolar disorders was 4.4% [8].

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We will see later that several lines of evidence suggest that the risk for BPD among depressed outpatients in psychiatric and primary care settings may be as high as 20% or 30% [5,9,10].

Subtypes of bipolar affective disorder Bipolar I disorder ‘‘Classic’’ manic-depressive illness or bipolar I disorder is only one subtype of this diverse mood disorder. Patients who have bipolar I disorder have experienced at least one manic or mixed episode (mixed episodes are defined by concurrent manic and depressive episodes), and usually have also had one or more major depressive episodes. During a manic episode, the patient demonstrates a persistently and abnormally elevated, expansive, or irritable mood for at least 1 week, and frequently requires hospitalization. Specific manic symptoms include inflated self-esteem or grandiosity, a decreased need for sleep, racing thoughts, more rapid speech, increased activity/agitation, and increased participation in pleasurable or excessive risk-taking activities. Three or more of these criteria in addition to elevated, expansive, or irritable mood must be met for a DSM-IV bipolar I, manic episode diagnosis. Patients are unable to function in their usual roles during a manic episode (Box 1). The typical expression of bipolar I disorder is characterized by the historical presence of at least one manic or mixed episode, embedded within the

Box 1. Acute bipolar maniaa A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary) At least three (four if irritable mood) of the following: Inflated self-esteem or grandiosity Decreased need for sleep More talkative than usual Flight of ideas or racing thoughts Distractibility Increase in goal-directed activity or psychomotor agitation Excessive involvement in pleasurable activitiesdpotential for painful consequences  Causes a marked impairment in occupational or social functioning a

Criteria established by the DSM-IV.

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chronological pattern of recurrent major depressive episodes. Although psychotic features may commonly be seen with severe depressive or manic episodes in BPD, they are not present during periods of euthymia (normal, healthy mood). This helps to distinguish BPD from schizoaffective disorder or schizophrenia. Fulminant episodes of mania do not commonly escape detection. Given the disruptive nature of the symptoms described above, the manic patient calls attention to himself, becoming unable to function in his usual capacity, and frequently requiring psychiatric hospitalization for stabilization. Management of acute mania in the outpatient setting is extremely difficult, and is not ordinarily recommended. Unfortunately, patients who have bipolar I disorder may not recall or report past manic episodes when being evaluated by a clinician when euthymic or depressed. This contributes to missed diagnosis of BPD in the depressed patient. Bipolar II disorder Bipolar II disorder is diagnosed when an individual experiences at least one hypomanic episode (Box 2) in addition to one or more major depressive episodes. By DSM-IV definition, patients who have bipolar II disorder have never experienced a full manic or mixed episode. Hypomania is different from mania in several ways. General impairment in hypomania is less severe than that seen in mania, with hypomanic patients having fewer or milder lapses of judgment than manic patients. Patients who have hypomania frequently respond to outpatient treatment, and may not require urgent Box 2. Hypomanic episodea A distinct period of persistently elevated, expansive, or irritable mood, lasting at least 4 days, that is clearly different from the usual nondepressed mood At least three (four if irritable mood) of the following: Inflated self-esteem or grandiosity Decreased need for sleep More talkative than usual Flight of ideas or racing thoughts Distractibility Increase in goal-directed activity or psychomotor agitation Excessive involvement in pleasurable activitiesdpotential for painful consequences  Causes an unequivocal change in occupational or social functioning, although not marked impairment a

Criteria established by the DSM-IV.

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hospitalization, as is often the case with mania. In other words, hypomanic patients do not experience major disability during the episode. Often they believe that they are more capable of increased productivity, whereas people familiar with the hypomanic individual are able to observe clear changes in their mood and behavior, such as irritability, hyper-talkativeness, or excessive activity, often at odd hours when combined with a decreased need for sleep. Hypomania may loosen inhibitions in the affected individual, contributing to impaired judgment in matters of financial or sexual discretion. Hypomania may prove difficult to diagnose using current DSM-IV diagnostic criteria, particularly given the lack of sound data to support the 4-day threshold for episode duration. Studies suggest that a threshold of 2 days’ duration for hypomania has higher validity, with a modal duration of 1 to 3 days [11]. Compared with mania, the less severe expressions of hypomania with relatively preserved functionality lead to a principal differential diagnosis of hypomania from ‘‘normal happiness,’’ irritability, and personality disorders. Indeed most patients do not view hypomanic periods as being symptomatic of an illness, more commonly believing these times to be interludes of wellness and transient relief from the depressions. Clinicians should be aware of this when attempting to screen for past hypomanic episodes, focusing on the connections between hypomanic symptoms and related behavioral consequences such as atypical impulsivity, inappropriate demeanor, or unusual hyperactivity [12]. Many believe that if BPD truly is unrecognized or underdiagnosed, it is primarily because of the failure of identifying hypomania. In a study of the French Clinical Epidemiology of Depression (EPIDEP) database, a DSM-IV bipolar II disorder diagnosis could be made in 22% of nearly 500 patients who had major depressive disorder at their initial interview [13]. After a second interview 1 month later, supplemented by more detailed evaluation and collateral information from significant others, 40% of patients were diagnosed within the bipolar II spectrum. As a note of caution and for diagnostic balance, clinicians must consider external circumstances (such as life triggers or substance abuse) and collateral sources of information before concluding that a patient’s subjective report of a few days’ of increased energy, irritability, and racing thoughts represents a genuine hypomanic episode as part of a bipolar II or bipolar spectrum illness. If there is a clear pattern of ‘‘hypomanic symptoms’’ tied only to such triggers or psychotropic precipitants, then diagnosing BPD should be deferred while these factors are further explored and addressed, especially if collateral sources are not strongly supportive of historical hypomania. Cyclothymic disorder Cyclothymic disorder is a chronic, fluctuating mood disturbance characterized by numerous periods of distressing hypomanic and depressive symptoms. These periods of mood disturbance may meet criteria for a hypomanic

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episode, but are not sufficient in number, severity, duration, or pervasiveness to satisfy criteria for manic or major depressive episodes, as defined for bipolar I and II disorders. The required duration of this pattern of mood symptoms is 2 years (1 year in children/adolescents) for the DSM-IV diagnosis. Cyclothymic disorder usually has an insidious onset and a chronic course. According to the DSM-IV, an estimated 15% to 50% of patients who have cyclothymia subsequently develop bipolar I or II disorder [14]. Bipolar disorder, not otherwise specified Bipolar disorder not otherwise specified (NOS) is a subtype of BPD that includes patients who experience bipolar symptoms that fall short of full criteria for a particular BPD, as outlined above. BPD, NOS is most commonly used to describe a patient who has recurrent depressions who has also experienced hypomanic symptoms that have lasted less than the DSM-IV–required 4-days. Other examples include recurrent hypomanic episodes without intercurrent depressive episodes; a manic or mixed episode superimposed on schizophrenia, delusional disorder, or other psychotic disorder; or situations in which a clinician concludes that BPD is present, but cannot determine whether it is primary or secondary to a medical condition or substance abuse. In practice, clinicians often use the terms BPD, NOS and ‘‘atypical BPD’’ interchangeably. Bipolar spectrum disorder ‘‘Bipolar spectrum’’ disorder or illness is a term commonly used to describe the full range of suspected phenotypes or symptomatic manifestations expressed by patients who have BPD, recognizing the significant heterogeneity of this population in terms of symptomatic episodes and severity, patterns, and cyclicity. Opposition to the use of this term commonly centers on the argument that overly broad inclusion of such a diverse grouping of patient types dilutes the meaning of ‘‘true’’ manic-depressive illness, usually associated with bipolar I disorder. Indeed, care must be taken to not simply include individuals who have moody temperaments into any categorization of a mental disorder such as BPD or bipolar spectrum disorders. Some individuals who have hyperthymic temperaments or personalities may provoke consideration of bipolarity simply because of their frequent displays of the triad of high energy, excessive cheeriness, and overconfidence. If only ‘‘hyperthymic’’ and without other mood disturbances, these individuals may merely be fortunate to have an adaptive sort of hypomania, and not BPD. The concept of a spectrum of bipolar illness, although evolving, is not new. The bookends of such a spectrum have often been referred to as ‘‘soft’’ versus ‘‘hard,’’ with the ‘‘softest’’ end of the spectrum including cyclothymic disorder and BPD, NOS [15]. This softer end of the bipolar spectrum is often viewed with a skeptical eye, with many arguing that

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a personality disorder may be a better diagnostic explanation. The experience of progressive description and validation of the bipolar II subtype should be remembered before dismissing the validity of ‘‘softer’’ BPD as a diagnostic entity, particularly given the recent discovery that bipolar II disorder may account for a disproportionately large portion of suicidal morbidity and mortality among all affective illnesses [16]. Box 3 summarizes a proposed definition of bipolar spectrum disorder by Ghaemi and colleagues [17]. This definition attempts to establish a comprehensive category of BPD that excludes clear-cut, recognized subtypes of BPD, such as type I, type II, and even pure cyclothymia, because it proposes to exclude spontaneous hypomanic episodes. In its current form, this Ghaemi definition of bipolar spectrum disorder more directly expands on the various features clinicians commonly encounter when describing atypical BPD or BPD, NOS. A more inclusive definition modifying Ghaemi’s is offered in Box 4. Here, the diagnostic theme of ‘‘lumping’’ rather than ‘‘splitting’’ is used, because all types of bipolaritydfrom classical to atypicaldare permitted, with an emphasis on recurrence and impact of the reported mood episodes. This modified definition is more practical in nature. Using the Ghaemi definition, a woman under 25 years of age with single postpartum depression, no past

Box 3. What is bipolar spectrum disorder? [17] A. At least one major depressive episode B. No spontaneous hypomanic or manic episodes C. Either one of the following, plus at least two items from D, below, or both of the following plus one item from D:  A family history of BPD in a first-degree relative  Antidepressant-induced mania or hypomania D. If no items from C, six of the following nine must be present:  Hyperthymic personality  Recurrent major depressive episodes (>3)  Brief major depressive episodes (average <3 months)  Atypical depressive features (eg, increased sleep or appetite)  Psychotic major depressive episode  Early age at onset of major depressive episode (before age 25)  Postpartum depression  Antidepressant tolerance  Lack of response to >3 antidepressant treatment trials From Ghaemi SN, Ko JY, Goodwin FK, et al. The bipolar spectrum disorder and the antidepressant view of the world. J Psychiatr Pract 2001;7:287–97; with permission.

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Box 4. Proposed new definition of bipolar spectrum disorder A. At least one major depressive episode, or one spontaneous manic episode B. If no spontaneous manic episodes, course of illness must include at least one of the following: 1. Distinct hypomanic episodes, preferably validated by collateral history and not antidepressant-induced 2. Recurrent major depressive episodes (>3 lifetime) or brief major depressive episodes (>3 single year), plus at least two items from D, below C. If hypomanic or manic episodes are only antidepressantinduced, then at least three items from D must be present. D. The following items may partially define bipolar spectrum disorder when present with elements noted above in B2 or C: 1. A family history of BPD in a first-degree relative 2. Hyperthymic personality 3. Atypical depressive features (eg, increased sleep or appetite) 4. Psychotic major depressive episode 5. Early age at onset of major depressive episode (before age 25) 6. Postpartum depression 7. Lack of response to >3 antidepressant treatment trials or repeated tolerance to antidepressants

manias or hypomanias, and a family history of BPD in a first-degree relative would qualify for the bipolar spectrum disorder diagnosis. This seems overly inclusive for immediate classification as a form of BPD, although such a patient may be suspected to be at increased risk for later development of more typical bipolarity. Under the modified definition here proposed, such a patient would not qualify for a bipolar spectrum diagnosis, unless there was some additional history of abnormal mood elevation (spontaneous or induced), or a more repetitive pattern of major depressive episodes, along with other associated features thought to suggest bipolarity. Put simply, any highly recurrent mood disorder characterized by instability of affect, energy, or behavior that is not classically unipolar should be considered as potentially within a spectrum of BPD. Depression: trademark of bipolar disorder Although the issue of what constitutes the manic/hypomanic side of the illness or how much ‘‘bipolarity’’ must be present to make an official

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diagnosis of either BPD or bipolar spectrum disorder continues to be debated, it is clear that the commonest denominator in most definitions and in the subjective experience of the disorder for patients is depression. Depressive symptoms are known to predominate the course of BPD over timed in bipolar I disorder, the time spent experiencing depressive symptoms is greater than the time spent with manic symptoms by a factor of 3:1, and in bipolar II disorder the depression/hypomania ratio is 37:1 [18,19]. Patients who have BPD are most likely then to present for evaluation and treatment in the midst of an active depressive episode. The accurate differential diagnosis of the depressive syndrome requires careful exploration for any historical mania or hypomania to begin to distinguish unipolar depression from bipolar depression. The proposed definitions and concept of bipolar spectrum disorder should also be considered. Data from US population surveys suggests that a substantial proportion of patients who have BPD (about 70%) have experienced delays in correct diagnosis, with about one third of patients who have BPD waiting a decade or longer to be diagnosed [20,21]. This 10-year gap before BPD diagnosis has been reported in Australia as well [22]. The most common misdiagnosis during this delay is unipolar major depressive disorder. The delay in accurate diagnosis appears to be a problem across a wide range of health care. Increasing reports from specific population studiesdprimary care, general psychiatry clinics, and private practice settingsdhave observed rates of BPD or risk for BPD between 10% and 50% [23]. Many of these reports studied groups of outpatients who were thought to suffer with unipolar major depression and were receiving standard antidepressant therapy. It is noteworthy that in both the primary care outpatient study by Hirschfeld and colleagues [10] and the multi-site psychiatry outpatient study by Calabrese and colleagues [9], around 20% of outpatients diagnosed with and treated for MDD screened positively for BPD risk. Furthermore, this screen positive rate was not significantly affected by the number of prior antidepressant failures or patient demographics [9]. It is clear from the evidence and from clinical experience that depression is the trademark for BPD, dominating the long-term course of the illness and contributing to the disguise and delayed diagnosis of BPD. Why is differential diagnosis of bipolar disorder from major depressive disorder critical? As has already been reviewed, BPD is characterized by abnormal elevations and depressions of mood and behavior, with depressions being more common than elevations irrespective of bipolar subtype. A single or recurrent major depressive episode in and of itself does not allow for the differentiation of unipolar from BPDdthe criteria for a major depressive episode are identical for the two mood disorders. The syndrome of a depressive episode warrants full exploration for potential other causes. One must

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first exclude depression caused by a general medical problem (such as hypothyroidism) or substance-induced depression (such as alcohol or medication), adjustment disorders, grief, psychosocial factors, or personality disorders, before considering unipolar versus bipolar depression. Failure to arrive at a correct diagnosis for a depressive episode may lead to ineffective treatment, and in terms of misdiagnosed bipolar depression that is treated as unipolar depression, may even be harmful. The most commonly prescribed form of pharmacotherapy treatment for the depressed phase of BPD remains antidepressant monotherapy, despite the lack of evidence to support such practice and despite concerns about their safety in the depressed patient who has BPD [24]. In naturalistic treatment settings, the use of antidepressants has been associated with a worsened course of BPD, by precipitating manic/hypomanic reactions or more rapid cycling of mood disturbance [25], and may be linked to the delays in initiating appropriate pharmacotherapy or increased risk for suicide. Even when antidepressants are prescribed along with mood stabilizers for BPD (discussed below), there should be concern for potential destabilization of mood. Although certainly not all or even the majority of patients will experience switching with antidepressants, some are more sensitive to this adverse effect. It has recently been reported that the incidence of antidepressant-induced switches to mania or hypomania, even when combined with a mood stabilizer, was around 20% over just 10 weeks, with a rate nearly twice that when the antidepressant was continued out for a full year [26]. The risk for such switching on antidepressants is higher in bipolar I disorder than in bipolar II disorder. Judicious use of antidepressants, always in combination with a mood stabilizer, and perhaps for only brief durations for bipolar depression, is warranted.

Impact of bipolar disorder and suicide risk Statistics from the World Health Organization often include BPD among the top 5 or 10 leading causes of disability-adjusted life years worldwide among people aged 15 to 44 [27]. The total lifetime cost for people who have BPD with illness onset in 1998 was estimated at $24 billion [28]. Countless studies have consistently found significantly elevated rates of dysfunction, disability, morbidity, and mortality associated with BPD, with the burden of depression estimated to carry most of the weight. Up to one half of all individuals who have BPD have been estimated to make at least one suicide attempt in their lifetimes, although the historically quoted figure of completed suicides in approximately 15% of all patients who have BPD seems to have declined over the last 1 or 2 decades, perhaps because of advances in treatments [29–31]. Genetic studies have linked certain susceptibility genes to predisposition for suicide in families that have BPD pedigrees [32]. Although many factors likely are associated with an

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increase in risk for suicide in BPD, a history of alcohol abuse and deterioration in function [31] and the depressed phase are known to elevate risk [33]. Managing suicide risk by exploring risk factors can be helpful, although the presence of human suffering may be the most sensitive indicator of heightened suicide risk, so it should not be surprising that suicide is more common during the painful depressive episodes than during mania or hypomania, especially given the predominance of depression with any subtype of BPD [34,35]. Early identification of BPD, commonly via differentiation of bipolar depression from unipolar MDD, is of paramount importance to initiate proper treatment in the hopes of effecting improvements in further reduction of suicide rates in BPD.

Implications for primary care As noted in the introduction, the majority of mental health care in the United States is delivered in the primary care setting. Particularly critical then is the ability of PCPs to, at a minimum, attempt to differentiate unipolar from bipolar depression before starting any pharmacotherapy for the patient experiencing a depressive episode. ‘‘Ruling out’’ BPD or assessing for the presence of any features of bipolarity should be considered standard of care in the management of the depressed patient. An evaluation of 187 patients at three primary care mood disorder clinic sites during a 60-month period revealed that the most common primary diagnosis was of BPD (39%) [36]. Major depression was diagnosed in 24% of patients, whereas 11.8% had anxiety disorders (which included obsessive compulsive disorder, generalized anxiety disorder, panic disorder, and posttraumatic stress disorder). Attempted suicide was reported in 15% of these patients. More recently and in a larger sample (n ¼ 1157) of adult patients seeking primary care at an urban clinic in the United States, the lifetime prevalence rate for BPD was reported to be about 10% through screening of the waiting room population [37]. Almost one fifth (18.8%) of the patients who screened positively for BPD reported suicidal ideation during the 2-week period before their primary care clinic visit. Failure to recognize BPD among depressed outpatients has been reported to occur commonly in the primary care and other medical treatment settings. In a large study of 649 outpatients being treated for depression with antidepressants in the Family Medicine Clinic at the University of Texas Medical Branch at Galveston, 21.3% of those patients screened positively for BPD, and therefore were at risk of having been misdiagnosed with and treated for unipolar major depression [10]. In a separate study, Ettinger and colleagues [38] found bipolar symptoms in 12% of community-based epilepsy patients, with a 25% rate of being unrecognized by the treating neurologist. Screening for BPD in a

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fibromyalgia clinic in Cleveland found that perhaps as many as 26% of these patients were at risk for BPD [39]. Misdiagnosis can prevent the patient who has BPD from receiving focused treatment with medications thought more suitable and safer for them, namely mood stabilizers such as lithium, divalproex, lamotrigine, carbamazepine, and atypical antipsychotics. As mentioned previously, the use of antidepressant medicationsdeither alone or in combination with a mood stabilizerdmay aggravate BPD, or may simply be ineffective at managing acute bipolar depression [25,40].

Making the diagnosis of bipolar disorder in primary care A simple, cross-sectional interview may not be of particular benefit when sorting through the differential diagnosis of a single depressive episode. Identification of a manic or hypomanic episode through longitudinal contact and repeated interviews with the affected individual, or combined with collateral history gathering from significant others, affords greater diagnostic sensitivity. Lack of insight during a manic episode is common, and is a major misleading factor in the diagnostic process [41]. Interviewing relatives may moderate this problem, with family known to report manic symptoms twice as frequently as self-report by patients themselves [42]. Further complicating matters, patients do not always present with clearly defined episodes or episodes that are typical for a DSM-IV–defined BPD. Therefore, it is important to keep the concept of a spectrum of BPD discussed earlier in mind when working through the differential diagnosis on initial assessment and throughout follow-up. Many patients will present to their PCP in relatively ‘‘mixed’’ statesd experiencing both major depressive and manic symptoms simultaneously or in rapid alternating fashion. It is not uncommon for patients who have BPD in the primary care setting to present with a mixed constellation of mood symptoms, along with anxiety and multiple physical complaints. Bipolar episodes may sometimes include psychotic symptoms, such as hallucinations and delusions, more commonly seen in manic than in depressed phases. The first presentation of BPD is usually depression rather than mania. Some patients may not recall past manic episodes, or choose not to disclose them because of embarrassment. Between full-blown manic and depressive episodes, patients may also experience subsyndromal depressions or hypomanias. The resolution of an episode, on its own or with treatment, may be a normal mood state (euthymia), or a switch from depression to mania or vice versa. Individual patients who have BPD may experience some or all of these various phases of illness, and the timeline for mood changes can be days, weeks, months, or years. The key position and insights held by the PCP in the lives of patients and their families may allow for improved detection of the bipolar form of depression.

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Screening tools for bipolar disorder? A complete and thorough history obtained by a seasoned clinician and corroborated by collateral sources of information cannot be replaced by any screening instrument or test. Similarly, practically useful screening tests cannot approach the sensitivity and specificity of validated diagnostic assessments most often used in research. The use of screening tests for BPD should not be considered the solution to identifying the disorderdthe tool’s users must possess or improve clinical skills required to properly interpret and apply the results of such screening tests. Otherwise, simply equating a positive or negative screen with the presence or absence of the disorder will lead to many errors. The Mood Disorder Questionnaire (MDQ) is a validated screening instrument that presents a symptom checklist of DSM-IV criteria for mania/hypomania, which respondents are asked to either endorse or deny experiencing at any time [43]. Those endorsing sufficient numbers of experienced symptoms who also endorse having symptoms occur or cluster together in time, as well as leading to significant dysfunction, are considered positive screens on the MDQ for BPD. The MDQ is widely available for use and can be found online (http://www.recognizebipolar.com/prof_asp/mdq/ or http://www.epocrates.com/products/medtools/bipolarscreening.html) in both English and Spanish versions. Recently the MDQ has been validated as a screening instrument in an adolescent population through completion of the instrument by parents about their children’s’ symptoms [44]. An alternate screening tool is the Bipolar Spectrum Diagnostic Scale (BSDS). This simple-to-use, one-page story depicts typical mood swing experiences and asks patients to place a check-mark at the end of each sentence that agrees with their own experience [45]. The BSDS may also be found online (http://www.psycheducation.org/depression/BSDS.htm). Use of screening instruments must be combined with appropriate clinical suspicion and fund of knowledge. The MDQ or BSDS should not be considered diagnostic instruments, but can aid in the process of ruling in or ruling out bipolarity when evaluating the depressed patient. Clinical clues to bipolar disorder Given the well-known preponderance of time spent symptomatically depressed in BPD, the first and foremost clue to the presence of BPD risk is depression itself. The historical course of the mood disorder may also provide diagnostic clues. Patients who have BPD are more likely than their unipolar counterparts to have experienced their first mood episode at an earlier agedusually a depression before the age of 30 [46]. In addition, patients who have BPD suffer more recurrent episodes overall, and spend less time well in between episodes. The pattern of illness may be mostly highly recurrent depressions, with only brief, sometimes subtle, hypomania, as in bipolar II disorder or bipolar spectrum disorder.

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A family history of BPD is more likely found in patients who have BPD than in those who have MDD. The presence of a family history of BPD in a patient who has criteria for major depression, even in the absence of a prior mania or hypomania, should alert the clinician to the higher risk for bipolarity [47]. More care and purposeful treatment for depression in this type of patient is necessary. In some depressed patients who have complex histories in whom BPD cannot clearly be ‘‘ruled-in’’ based on DSM-IV criteria, a past history of chaotic psychosocial events and development, multiple jobs, multiple marriages, multiple geographic relocations, bankruptcies, and overall unpredictability of behaviors might be more indicative of BPD than MDD. These variables may represent sequelae of living with the more chronic and recurrent bipolar mood disorders, compared with MDD, in which more extended periods of wellness are common. The presence of medical comorbidities in the depressed patient may also point toward BPD. Data analysis from the recent Canadian Community Health Survey (N ¼ 36,984) found that among the 2.4% of individuals who had a lifetime history of a manic episode, rates of chronic fatigue syndrome, asthma, chronic bronchitis, hypertension, gastric ulcer, multiple chemical sensitivities, and migraine headache were significantly higher than those who had no past manic episode [48]. Individuals who had medical comorbidities with BPD were much more likely to experience psychosocial distress or dysfunction and to use health care services. In migraine comorbid with BPD, even greater dysfunction and medical service use (both primary care and mental health) was observed in men compared with women [49]. Depressed outpatients who have medical comorbiditiesdparticularly migraine, irritable bowel, or fibromyalgiadshould be screened more carefully for BPD. Compared with unipolar MDD, individuals who have BPD are much more likely to have lifetime histories of substance abuse [6]. Although differentiating substance-induced mood disorders from primary mood disorders can be difficult, the clinician should make every effort to outline a chronological history of mood and substance use, not quickly dismissing mood instability as drug-related unless absolutely certain. Because the majority of patients who have BPD have current or past alcohol or substance abuse problems, some combination of primary mood and substance-induced or substance-aggravated mood symptoms should be expected as the rule, rather than the exception. The response of patients to prior treatments with antidepressant medications may also aid in differentiating bipolar from unipolar depression. Patients who have BPD who have been given antidepressant medications may be more likely to experience highly variable results, ranging from multiple drug treatment failures/resistance to either erratic responses or remarkably fast, sudden, brief relief of depressed mood (sometimes within days to weeks of starting the antidepressant). These treatment-refractory, depressed patients or those who have erratic responses to the drugs should be more carefully assessed for the potential presence of BPD.

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Many clinicians believe that the likelihood of a bipolar diagnosis in the depressed patient increases with increasing numbers of antidepressant failures; however, the results of a recent, 60-site study of 602 individuals being treated for unipolar MDD by their outpatient psychiatrists found that the rate of positive screening using the MDQ was unaffected by the number of failed antidepressant trials or regimens [9]. Nearly 20% of these depressed patients were found to be at risk for BPD, based on a positive MDQ. The positive predictive value of the MDQ in this cohort of patients who have depression is enhanced by the increasing suspicion or prior probability of BPD, and in practical application, the clinician with a patient failing any antidepressant treatment may find nearly one in five with elevated risk for or diagnosis of BPD. It is important to note that the average number of failed antidepressants was approximately three, but that the screen-positive rate did not significantly change based on number of antidepressant failures. Any time a depressed patient fails to respond to treatment, the clinician should review the diagnosis before initiating the next pharmacotherapydin the case of BPD, this has clear implications, given the risk of precipitating manic switches with antidepressant monotherapy. Failing to adequately review risk for BPD will further delay appropriate diagnosis and initiation of mood stabilizer therapy. Based on the above study, clinicians should have a higher index of suspicion for the presence of BPD in depressed patients who have failed standard antidepressants and have recent onset (within 5 years) of problems with depression, comorbid anxiety, a family history of BPD, a history of legal problems, and feelings of people being unfriendly toward them. This last risk factor may represent a learned cognition, as a consequence of impaired relationships caused by past overactive or inappropriate behavior that can be seen in BPD, particularly given the fact that these depressed patients may not have been correctly diagnosed or treated for BPD. Perhaps the most practically useful overview of the difference between BPD and MDD lies within the general clinical picturedlongitudinally and not cross-sectionallydof the phenomenology of the mood disorder itself. The generally greater instability of the clinical portrait of bipolar depression may point toward the diagnosis of BPD. Bipolar depression tends to be more intense, more unstable, more clinically complex, and less predictable in course than its unipolar counterpart. This ‘‘tempestuous’’ nature may be a signature for bipolar depression, particularly in bipolar II disorder, in which despite hypersomnia, patients may remain excessively psychomotor activated [50]. Enhanced clinical acumen, perhaps augmented by the use of screening tools, can reduce the rate of misdiagnosis. Treatment Despite the effectiveness of treatments that are currently available, only a fraction of patients who have BPD receive treatment. An in-depth

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exploration of the treatment of BPD is beyond the scope of this article. Evidence-based guidelines that address treatment options and algorithms have been published extensively, and continue to receive updates as emerging data change directions of treatment, particularly for acute bipolar depression. The American Psychiatric Association Practice Guidelines for the Treatment of Bipolar Disorder await revision, and more recent guidelines can be found in the current literature (Canadian Network for Mood and Anxiety Treatments [CANMAT]; Texas Implementation of Medication algorithms [TIMA]) [51,52]. The majority of guidelines published to date and expert consensus caution against the use of traditional antidepressant medications as monotherapy for acute bipolar depression. To date, there has been no clear and convincing evidence that antidepressants are both safe and effective for acute bipolar depression, and as of May 2007 only two US Food and Drug Administration (FDA)-approved medications exist for this indication (olanzapine-fluoxetine combination and quetiapine). Although practice guidelines can and will be updated, the focus of initial treatments for acute bipolar depression will remain on a small handful of mood stabilizers (lithium, anticonvulsants, and atypical antipsychotics), either alone or in combination with antidepressant medication.

General treatment principles The deliberations for consultation and referral for BPD are similar to those for other illnesses. Patients who require immediate stabilization or who are a danger to self or others deserve consideration for immediate referral to a mental health specialist. For less acutely ill patients, PCPs may want to make a provisional diagnosis of BPD and initiate appropriate treatment while awaiting transition to the psychiatrist’s care. Other patients may be treated entirely in the primary care setting, depending on the training, experience, ability, and motivation of the individual PCP. PCPs with established skill to treat BPD may still choose to refer difficult or exasperating patients, particularly if a therapeutic alliance is problematic. Creating a positive therapeutic alliance with a patient can enhance the treatment plan and improve adherence and chances for recovery. Clear and direct communication is a key ingredient in the creation of an environment necessary for a good therapeutic alliance. Encouraging patients to participate in activities and therapies, particularly peer-to-peer groups, can be very helpful. Providing education to patients who have BPD and to their families can foster treatment adherence, promote destigmatization, and help individuals become active and informed participants in the management of their illness. Expectations about treatment should be managed by discussion of the treatment options, therapeutic effects, possible adverse effects, and likely need for long-term medication. Physicians should not

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settle for partial benefit, or be dismayed by not achieving full remission. Full functional recovery is likely to take several months or even years. Knowledge about the course and pattern of an individual’s bipolar disorder may allow new episodes and high-risk situations to be identified early and managed more effectively. Individuals may have unique triggers and behavioral harbingers of poor control. Information from family and other third parties should be solicited when assessing risk, especially suicide risk, substance use, and social isolation. The need to recognize and manage risky behavior (eg, limit access to dangerous machinery, cash, credit cards, checking accounts) should be discussed. The family and other caregivers should be assisted to recognize warning signs and risky situations. Making major/lifechanging decisions when in a depressive or manic episode should be avoided. Self-monitoring through the use of personal logs or daily diaries of mood, medication, sleep patterns, and activities of daily living should be promoted. Adherence with treatment for patients who have BPD remains a longterm challenge. Reported rates of nonadherence with prophylactic medication management among patients who have BPD range from 18% to 52%, with a median prevalence of 44.7% [53]. PCPs may help promote adherence with medication and long-term treatment simply through longitudinal therapeutic alliance with their patients, particularly via simple exchange of knowledge about the disorder, which is known to enhance treatment adherence [53].

Pharmacotherapy ‘‘Mood stabilizers’’ The pharmacotherapy of BPD centers on the use of medications that have come to be called ‘‘mood stabilizers.’’ This term is not recognized by the FDA, and a single widely agreed upon definition does not exist. Varying definitions for a ‘‘mood stabilizer’’ have been increasingly debated over the past decade. Although many believe that the term was first used in relation to lithium, its first appearances in the literature were with regard to the antipsychotic chlorpromazine and the tranquilizer aminophenylpyridone [54,55]. The ideal mood stabilizer would work in all phases of the illness and in all stages of treatmentdfrom treating acute depression, mania, hypomania, and mixed states to preventing all abnormal elevations or depressions of mood. This ideal mood stabilizer would not aggravate or worsen any feature of the illness (ie, precipitate depression or mania), or lead to rapid cycling or cycle acceleration. In other words, the best mood stabilizer would work in all four treatment roles in BPD, treating the highs and lows as well as preventing the highs and lows. The picture becomes more complex if we consider the need to treat the full range of bipolar spectrum disorders. To date no such ideal mood stabilizer exists, although many would argue that lithium comes closest [56].

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Currently available psychotropic agents are partial mood stabilizers at best. Lack of mood destabilizing effects plus efficacy in at least one area of BPD management should allow for use of the term ‘‘partial mood stabilizer.’’ A partial mood stabilizer may be defined as any pharmacologic agent with evidence of efficacy in at least one area of bipolar disorder management (acute depression, acute hypomania, acute mania/mixed, or maintenance) and no evidence suggesting that it is associated with increased risk of mood switching or cycle acceleration. The term ‘‘mood stabilizer’’ should be reserved for use in general discussions about the search for an ideal agent that is effective in all poles of illness, recognizing that no complete mood stabilizer has yet been discovered. The available partial mood stabilizers are predominantly agents that have demonstrated anti-manic efficacy. Less evidence exists to support their use for depression in BPD, although recent advances have led to newly approved treatments for this phase of the illness. Mania/hypomania/mixed states Mania is generally more easily managed than depression, and many more approved drug options exist for mania. Table 1 lists the commonly used drugs that are approved by the FDA to manage BPD, and includes known antimanic agents. Psychiatric hospitalization is usually necessary to manage mania. There are no approved treatments for hypomania, although most clinicians’ experience suggests that the same treatments used for mania, sometimes at lower doses, are usually effective [57]. The available evidence suggests that lithium, certain anticonvulsant or antiepileptic drugs (AEDs), and all of the atypical antipsychotic drugs are effective for acute mania, and may possess other therapeutic properties that could support calling them mood stabilizers. Clinicians typically will choose a single antimanic

Table 1 Medications approved in the United States for bipolar disorder Drug

Mania

Mixed

Maintenance

Aripiprazole Carbamazepine ER Chlorpromazine Divalproex DR Divalproex ER Lamotrigine Lithium Olanzapine Olanzapine-fluoxetine Quetiapine Risperidone Ziprasidone

X X X X X

X X

X

X X X X X

Depression

X

X

X X X X X

X X

Abbreviations: DR, direct release; ER, extended release.

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agent from Table 1 to treat hypomania or mild mania, whereas two or more agents may be required for more severe cases of acute mania. Mixed episodes (mania plus depression) can be challenging, and are best approached by first stabilizing the manic symptoms using one or more of the medications from Table 1. After resolution of the manic portion of the episode, if any residual symptoms of depression are present, then appropriate use of an antidepressant medication added to the regimen can be considered. Because manic symptoms are still fresh in such a patient who had a mixed episode, cautious use of antidepressants is recommended to minimize the risk of reactivating the mania. Even with bipolar spectrum disorders in which the mixed state can be mostly depression with just a few manic or hypomanic symptoms, such an approach is still suggested. There has been a surge in the number of medications effective to treat mania acutely in the past decade, mostly because of the appearance of atypical antipsychotics and their demonstration of efficacy for bipolar mania and mixed states. All of the atypicals, lithium, carbamazepine, and divalproex have had studies supporting their role as antimanic agents. A review of the positive monotherapy studies that have produced evidence from large, randomized, double-blind, placebo-controlled studies with these agents can be found elsewhere in the literature [58]. Analyses of these studies find that these agents produce fairly robust clinical effects, with the numbersneeded-to-treat (NNT) ranging from 2.7 to 6.7, and no remarkable differences existing between the drugs in terms of their acute antimanic effects. On a more practical level relevant to primary care, management of acute bipolar mania should typically include referral to psychiatry, and likely hospitalization. Bipolar depression Although some of the aforementioned practice guidelines or algorithms may list lithium and lamotrigine as first-line treatments for acute bipolar depression, it should be noted that the only approved medications for this indication are the olanzapine-fluoxetine combination and quetiapine. No traditional antidepressant in monotherapy has ever demonstrated both safety and efficacy in bipolar depression, and these antidepressants are not formally indicated for such usage by the FDA. The clinical approach to managing bipolar depression, once recognized, has been guided for many years by extrapolations and assumptions based on evidence from unipolar major depression studies. The use of agents deemed ‘‘antidepressants’’ based on efficacy in treatment trials for unipolar major depression has not been well-studied for bipolar depression. From 1968 to 2001, there were only 12 randomized, placebo-controlled trials of traditional antidepressants in the treatment of bipolar depression [59]. Only 5 of these studies reported the antidepressant studied to be more effective than placebo. As described earlier, concerns for antidepressant-induced

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switching or destabilization of mood appear to be valid to a certain extent. A recent effectiveness trial of adjunctive antidepressant treatment for bipolar depression found no efficacy for the use of the agents, even when the common clinical practice of adding the antidepressant to a mood stabilizer was employed [40]. Currently, evidence supports initial management of acute bipolar depression with either quetiapine or olanzapine-fluoxetine combination. All other approaches remain ‘‘off-label,’’ including the use of lithium, lamotrigine, or traditional antidepressants. In the primary care setting, after recognition of acute bipolar depression treatment with one of the FDA-approved agents should be considered. For those patients who do not respond to these first steps or who present with more severe depression, combination with lithium or lamotrigine may be reasonable while awaiting psychiatric consultation. It is clear that bipolar depression remains an area of unmet need in terms of therapeutics. Compared with the management of acute mania, there are relatively limited data to provide a strong evidence base to treat bipolar depression, with the exceptions of olanzapine-fluoxetine combination and quetiapine. A review of the positive studies of acute treatment for bipolar depression based on evidence from large, randomized, double-blind, placebocontrolled studies can be found elsewhere in the literature [58]. Olanzapine-fluoxetine and quetiapine have demonstrated efficacy with NNTs ranging from 3.9 to 7.4, comparable to effective treatments for mania. Although lamotrigine was able to demonstrate efficacy for acute bipolar depression in one trial (NNT 4.5–8.3), these results have not been replicated [60]. Maintenance therapy in bipolar disorder Prevention of acute bipolar manic episodes through maintenance treatment is critical to minimize the deleterious and far-reaching consequences associated with mania. There remains significant debate as to the most appropriate treatments for prevention of future manic episodes. The most common practice is the continuation of the medications that resolved an acute manic episode, although acute manic episodes may be treated with a typical or atypical antipsychotic medication that is later discontinued and replaced with lithium or another mood stabilizer for maintenance. Some form of maintenance pharmacotherapy should be prescribed following acute manic episodes or other frequently recurrent and disruptive states such as hypomania. Given its highly recurrent nature and propensity for illness relapses and recurrences to be depressive, the ability to prevent depression could have a profound impact on ameliorating the burden of BPD. The 2003 FDA approval of lamotrigine for the prevention of mood episodes associated with bipolar disorder, with specific mention of preferential prophylaxis of depressive episodes, was a landmark event in the therapeutics of bipolar disorder. The approved availability of a treatment option other than lithium

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for this phase of preventative therapy is important, given the large unmet need in the treatment of bipolar depression and the relatively high rate of depressive relapse despite lithium maintenance. Of concern in the management of depressive risk is the potential for any medication to precipitate a manic switch or to destabilize the course of BPD. Significant debate exists over the long-term use of antidepressants in BPD, where controlled data is lacking to support efficacy, but there are data to suggest an unacceptably high rate of manic relapse during long-term follow-up of patients treated with antidepressants for maintenance [61]. Clinical use of specific partial mood stabilizers Lithium Clinical improvement with lithium in any phase of BPD is generally gradual in onset, with therapeutic response occurring no sooner than 7 to 14 days after it is started for manic patients. Lithium has a significant adverse effect profile that can complicate long-term management. These effects may be less apparent during acute treatment with lithium than during maintenance treatment. Pretreatment procedures and testing are recommended before beginning therapy with lithium: general medical history, physical examination and weight, blood ureal nitrogen (BUN) and creatinine determination, thyroid function studies, and pregnancy testing for women of child-bearing age. Lithium carries a teratogenicity category D warning. Electrocardiography and complete blood count measurement should be obtained for patients over the age of 40. Some experts recommend more detailed screening, to include fasting glucose determination and dehydration test with vasopressin to determine renal concentrating capacity. For treatment of acute mania, lithium should be dosed to achieve therapeutic plasma concentrations (sampled 12 hours after the last dose) between 0.8 and 1.2 mEq/L, avoiding toxic effects more commonly seen with levels at or above 1.5 mEq/L. A routine initial dosing regimen is the administration of lithium carbonate 300 mg three to four times a day with trough plasma level determination on day 4 or 5 of treatment, targeting the therapeutic range and watching for any signs of toxicity. A lower starting dose and slower titration are recommended in older patients and those with impaired renal function. When used to treat milder mania or hypomania, lower starting doses (300 mg twice daily) and lower blood levels (0.6-0.8 mEq/L) may sufficiently stabilize mood over a period of several weeks to months. Lower doses and levels of lithium may be sufficient when combination pharmacotherapy strategies, such as lithium plus an anticonvulsant or antipsychotic, are used. These lower doses may greatly reduce the frequency of troublesome side effects during early treatment, and thus enhance adherence. Although not well-studied, most recommendations for the use of lithium to acutely manage depression associated with BPD are to dose to a minimum

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serum lithium level of 0.8mEq/L. There is scant evidence available by which to compare the efficacy of lithium relative to standard antidepressants. The most common side effects of lithium are nausea, vomiting, tremor, diarrhea or more frequent stools, polydipsia, and polyuria. During acute treatment, gastrointestinal disturbances and tremor can be mitigated by slower dosing strategies. These adverse effects typically subside within 1 or 2 weeks, although on occasion they can persist. Worsening of any of these adverse effects, as well as the development of bradycardia, syncope, confusion, or ataxic gait, should prompt the clinician to immediately measure lithium blood levels and consider changes in dosing or treatment alternatives. Psoriasis, acne, and other skin/hair reactions have also been described in association with lithium therapy. Lithium toxicity may be heralded by emergence or aggravation of any of the above adverse effects, progressing to include one or more other symptoms such as coarsening tremor, sluggishness, slurred speech, parkinsonism, hyperreflexia, myoclonic twitches, and mental status changes. Early recognition of toxicity is critical, as is investigation of cause. The possibility of drug interactions with lithium must always be considered, particularly with thiazide (and possibly loop) diuretics, angiotensin converting enzyme (ACE) inhibitors, non-steroidal anti-inflammatory drugs, and other psychotropics. Antipsychotics Although typical antipsychotics can be used effectively to treat mania, there is very little evidence to suggest that they meet any definition of a mood stabilizer; however, growing evidence reviewed below suggests that one or more of the newer atypical antipsychotics may be considered mood stabilizers in the management of BPD. Randomized, placebo-controlled trials have demonstrated the efficacy of all five second-generation atypical antipsychotics (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole), and led to their FDA approval for the management of acute bipolar mania, with or without psychotic features. With the exception of quetiapine, they are all approved for mixed states in bipolar disorder. A recent meta-analysis of randomized controlled trials of these five atypical antipsychotics in the treatment of acute mania, as monotherapy or adjunctively, concluded that differences in efficacy between these agents are likely to be small [62]. Olanzapine. The antimanic dose of olanzapine is usually between 15 to 20 mg daily, although lower doses may be effective when used adjunctively with other mood stabilizers. During initial treatment of a severe manic episode in clinical practice, off-label doses of 30 to 40 mg daily may be required, which can be safely reduced once the acute episode has resolved. Olanzapine monotherapy has modest antidepressant effects, whereas the olanzapine-fluoxetine combination became the first FDA-approved therapy for acute bipolar depression. Olanzapine-fluoxetine can be initiated at 6 and

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25 mg/day (olanzapine 6 mg with fluoxetine 25 mg), with increases to 6 and 50 or 12 and 50 mg/day after at least 1 day at each dose. Olanzapine monotherapy is approved to treat BPD long-term for maintenance. Risperidone. The mean modal antimanic doses for risperidone as monotherapy or add-on therapy ranged from 4 to 6 mg/day, with the lower end of the range used when combined with another mood stabilizer. Again, clinical practice and individual patient needs may demand doses that are above or below this dose range. Very little evidence exists to support risperidone for use in acute bipolar depression. Maintenance treatment with risperidone is off-label. Quetiapine. In both monotherapy and adjunctive therapy indications for bipolar I mania, the recommended dose for quetiapine is 600 mg/day, following a twice daily titration schedule over 5 days after starting with 50 mg twice a day. Currently, the use of quetiapine in maintenance is not yet approved. Quetiapine recently was approved as the first monotherapy treatment for acute bipolar depression. Although both the 300 mg every night and 600 mg every night doses demonstrated efficacy superior to placebo in the registration trials, the 300 mg daily dose is the recommended dose. Quetiapine can be initiated at 50 mg/day, and titrated to achieve a target dose of 300 mg/day by day 4, with single evening or bedtime dosing. Ziprasidone. Ziprasidone may be started at 40 mg twice a day (given with meals to enhance absorption) and increased up to 160 mg/day within the first week, with an average dose of around 120 mg/day in study responders. At the present time, evidence is lacking to recommend routine use of ziprasidone for the depressed phase of BPD or in maintenance. Aripiprazole. Treatment of manic or mixed episodes in bipolar disorder with aripiprazole may commence with 15 to 30 mg/day, with responders requiring an average daily dose near 30 mg/day. Only preliminary data from small studies exists regarding aripiprazole for acute bipolar depression use [63–65]. Until more evidence emerges, we cannot assume that all atypical antipsychotics do, or do not, have antidepressant efficacy for acute bipolar depression; however, aripiprazole is approved for maintenance therapy of BPD. Tolerability and safety issues with atypicals Atypical antipsychotics generally have superior tolerability when compared with typical antipsychotics in the management of BPD. Sideeffect profiles vary among the different atypical agents, whereas monitoring needs remain the same. Of principal concern with longer-term use is the risk

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for metabolic derangements, notably weight gain, type-2 diabetes, and lipid elevations. Prior to initiating therapy for mania with any atypical antipsychotic, baseline assessment of type 2 diabetes mellitus risk factors and determination of fasting glucose, weight, waist circumference, and lipid profile are recommended. Although metabolic risk concerns may be less intense with short-term use to address either acute mania or depression, prolonged use must be accompanied by periodic monitoring of metabolic indicators. Antiepileptic drugs Reports of the beneficial behavioral effects associated with the use of AEDs in patients who have bipolar disorder, particularly for mania, date back to the 1960s. Discussions regarding the potential for some shared etiologic process between epilepsy and bipolar disorder, such as kindling, were common in the literature of the time. Theoretically, as in epilepsy, in which repeated subthreshold neuronal stimulation can generate an action potential that triggers a seizure, kindling in a patient who has BPD could produce activation of or switching to disordered mood statesdmania, depression, mixed states. The proposed reduction of kindling by AEDs such as carbamazepine, along with observations of positive ‘‘mood stabilizing’’ effects, led to widespread investigation of virtually every developed AED in BPD [66]. The AEDs are a heterogeneous group of medications that have demonstrated variable effects in the treatment of bipolar mania. Other than divalproex and carbamazepine, other AEDs have not demonstrated strong evidence to support routine use as antimanic agents. The antidepressant effects of AEDs in BPD are less well-studied, and there is very limited supportive evidence for their use in acute bipolar depression, although clinical practice often includes these agents in utilitarian fashion [67,68]. Most of the attention to date has centered on divalproex (and related compounds such as valproate) and lamotrigine, with very little controlled data regarding the use of other AEDs in acute bipolar depression. Divalproex. Before initiating treatment of BPD with divalproex, a general medical history with special attention to any past problems of hepatic or hematological nature should be obtained, as well as baseline liver profile, and complete blood cell count. Pregnancy screening should be conducted before starting divalproex, particularly given its FDA black-box warning of teratogenicity category D. Divalproex can be dosed with either an oral-loading or standard-titration strategy. For acute management of severely ill manic patients, divalproex oral-loading with a therapeutic starting dose of 20 to 30 mg/kg per day is suggested over standard, gradual titration schedules. Oral-loading typically achieves serum concentrations of valproic acid greater than 50 mg/L by day 2, which represents the low end of the therapeutic range of serum concentrations for this agent of 50 to 125 mg/L. Similar results can be obtained by

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using the extended-release preparation. Lower, divided doses are initially recommended (250 mg three times a day or 500 mg twice a day) for patients who have less severe mania or in elderly patients. Divalproex is not indicated for the management of acute bipolar depression, although some studies and clinical experience suggest that it may offer some measure of benefit. A more gradual oral dosing strategy should be used when used off-label for bipolar depression. Although commonly used as maintenance therapy, it does not carry the FDA indication in the United States. Adverse effects seen during initial therapy with divalproex are usually mild, transient, and easily managed. Gastrointestinal distress and sedation are the most commonly seen side effects during acute treatment, although other dose-related effects, including tremor and benign hepatic transaminase elevations, are occasionally encountered. Reduced dosage or slower upwards titration can be helpful, in addition to use of divalproex sodium formulation or extended-release divalproex instead of valproic acid may also lessen these side effects. Tremor may be minimized through dose reduction or concomitant beta-blocker medication. During acute treatment with divalproex, clinicians should consider the possibility of rare but potentially serious adverse effects such as irreversible hepatic failure, hemorrhagic pancreatitis, or hyperammonemic encephalopathy when patients experience severe abdominal distress, confusion, or delirium. Divalproex commonly displaces otherwise highly protein-bound drugs from their protein binding sites, requiring greater awareness of clinically significant drug interactions. Divalproex can also inhibit the metabolism of other drugs cleared by the liver. Most notably, it inhibits lamotrigine metabolism by 50%, resulting in the critical need to initiate lamotrigine at 50% lower doses when coadministered with divalproex. Carbamazepine. Before starting carbamazepine, a general history and physical examination should be performed, including screening for any history of liver disease or blood dyscrasias. Routine laboratories including complete blood count, liver profile, and electrolytes with creatinine should be obtained. More frequent monitoring is indicated in the elderly or in any individual on carbamazepine who develops fever, easy bruising or bleeding, weakness, or infection. Extended-release carbamazepine is approved to treat bipolar mania, with common off-label usage for acute bipolar depression and maintenance carrying less supporting evidence. There is no clear target serum level of carbamazepine for acute mania. Immediate release carbamazepine therapy may be started at a total divided daily dose of 200 to 600 mg, with incremental increases of 200 mg/day up to 1000 mg/day, followed by careful monitoring of blood levels, side effects, and clinical efficacy. The beaded, extended-release form may be started at 400 mg/day and increased as tolerated up to 1600 mg/day. Many factors

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can affect carbamazepine blood levels beyond direct dosing, including autoinduction of metabolism and significant drug interactions. During acute treatment with carbamazepine, the most commonly observed side effects are nausea, fatigue, blurred vision, and ataxia. More gradual initial titration of the dose may minimize these effects. Infrequently, liver transaminase elevations, rash, hyponatremia, and blood dyscrasias may complicate acute treatment. Lamotrigine. Initial reports of lamotrigine’s efficacy for acute bipolar depression were not replicated, and it is not an effective antimanic agent, making maintenance therapy its primary (and approved) role in the management of BPD. No pretreatment laboratories are required before initiating lamotrigine, although routine physical examination, basic baseline chemistries, and pregnancy testing are advisable. A history of hypersensitivity to lamotrigine is the only contraindication to use. The risk of rash must be discussed before initiating therapy with lamotrigine, and may be better informed by data from multicenter trials of lamotrigine in mood disorders. Calabrese and colleagues [69] reviewed data on 3153 patients treated with lamotrigine in mood disorder trials, compared rash rates with the 1056 placebo-treated patients, and found that rates of benign rash were 8.3% and 6.4% in lamotrigine- and placebo-treated patients, respectively. Rates of serious rash were 0% with lamotrigine and 0.1% with placebo. In the open-label setting, the overall rate of rash for lamotrigine was 13.1% and of serious rash, 0.1%. One mild case of Stevens-Johnson syndrome was reported in a patient treated with lamotrigine, and there were no cases of toxic epidermal necrolysis. Any lamotriginetreated patient developing any rash that cannot readily be explained by a known other cause(ie, contact dermatitis) should immediately discontinue lamotrigine and notify the treating physician before resuming therapy. In unclear or difficult cases, dermatologic consultation should be obtained before restarting or rechallenging with lamotrigine. Following a careful and gradual dosage titration schedule reduces the risk of rash. Lamotrigine should be initiated at 25 mg/day, with the first dosage increase to 50 mg/day 2 weeks later. Lamotrigine may be increased to 100 mg/day in week 5 and to 200 mg/day in week 6. The presence of enzyme-inducing drugs such as carbamazepine requires doubling of the lamotrigine dose, whereas concomitant administration with divalproex dictates a 50% reduction in lamotrigine dosing. Concomitant prescription of estrogen-containing oral contraceptives may lead to enzyme-induction and increased metabolism of lamotrigine, which may necessitate an increase in lamotrigine dose during the maintenance phase in some patients based on clinical circumstances. The most common side effects observed with lamotrigine are dizziness, ataxia, somnolence, headache, diplopia, blurred vision, nausea, and vomiting. These side effects are typically mild and rarely lead to treatment

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discontinuation. Decreasing the dose or slowing the rate of dose escalation may alleviate these bothersome side effects.

Summary Psychiatric illnesses are commonly encountered in the primary care setting, placing PCPs in key diagnostic and treatment roles. Although depression is now well-recognized by most PCPs, improved diagnostic accuracy is necessary, because BPD most often presents in the depressed phase. The proposed spectrum of bipolar disorders further complicates the evaluation of depression, because BPD is often misdiagnosed as unipolar major depression. Inadequate or failed treatment of BPD, especially bipolar depression, can dramatically lead to increased morbidity and mortality. Exploring historical factors, including personal history of manic/hypomanic symptoms and family history, can improve a clinician’s ability to recognize BPD. Screening instruments can be useful, albeit not diagnostic when used alone. Family involvement in the assessment of major mood disorders is necessary when trying to distinguish the cause of a major depressive episode. Although referral to a psychiatrist may be the most direct method of establishing a correct diagnosis and treatment plan, PCPs are often faced with initial diagnostic and treatment dilemmas, and patients may not follow through with psychiatric referral. Application of a more advanced knowledge base will allow the thoughtful PCP to establish a therapeutic alliance with a patient who has BPD or a bipolar spectrum disorder. Although many effective treatments exist for acute mania, referral to psychiatry and possible hospitalization are typically recommended for this potentially unpredictable and risky phase of the illness. Caution must be exercised when assessing and treating the depressed patient who has BPD, particularly given the elevated risk for suicide; however, initiation of appropriate partial mood stabilizers with known antidepressant properties can quickly begin to address this painful pole of bipolarity. Long-term maintenance medication is recommended for BPD, along with careful monitoring for any treatment-related adverse events.

References [1] Kraepelin E. Manic-depressive insanity and paranoia. Edinburgh (Scotland): Livingstone E&S; 1921. [2] Angst J, Marneros A. Bipolarity from ancient to modern times: conception, birth and rebirth. J Affect Disord 2001;67(1–3):3–19. [3] Regier DA, Narrow WE, Rae DS, et al. The de facto US mental and addictive disorders service system. Epidemiologic catchment area prospective 1-year prevalence rates of disorders and services. Arch Gen Psychiatry 1993;50(2):85–94. [4] Manning JS. Difficult-to-treat depressions: a primary care perspective. J Clin Psychiatry 2003;64(Suppl 1):24–31.

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[5] Manning JS, Haykal RF, Connor PD, et al. On the nature of depressive and anxious states in a family practice setting: the high prevalence of bipolar II and related disorders in a cohort followed longitudinally. Compr Psychiatry 1997;38(2):102–8. [6] Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA 1990;264(19):2511–8. [7] Hirschfeld RM, Calabrese JR, Weissman MM, et al. Screening for bipolar disorder in the community. J Clin Psychiatry 2003;64(1):53–9. [8] Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the national comorbidity survey replication. Arch Gen Psychiatry 2007;64(5):543–52. [9] Calabrese JR, Muzina DJ, Kemp DE, et al. Predictors of bipolar disorder risk among patients currently treated for major depression. MedGenMed 2006;8(3):38. [10] Hirschfeld RM, Cass AR, Holt DC, et al. Screening for bipolar disorder in patients treated for depression in a family medicine clinic. J Am Board Fam Pract 2005;18(4):233–9. [11] Akiskal HS, Bourgeois ML, Angst J, et al. Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders. J Affect Disord 2000; 59(Suppl 1):S5–30. [12] Benazzi F, Akiskal HS. Refining the evaluation of bipolar II: beyond the strict SCID-CV guidelines for hypomania. J Affect Disord 2003;73(1–2):33–8. [13] Hantouche EG, Akiskal HS, Lancrenon S, et al. Systematic clinical methodology for validating bipolar-II disorder: data in mid-stream from a French national multi-site study (EPIDEP). J Affect Disord 1998;50(2–3):163–73. [14] Diagnostic and statistical manual of mental disorders. 4th edition. Washington, DC: American Psychiatric Association; 1994. [15] Akiskal HS, Djenderedjian AM, Rosenthal RH, et al. Cyclothymic disorder: validating criteria for inclusion in the bipolar affective group. Am J Psychiatry 1977;134(11):1227–33. [16] Rihmer Z, Pestality P. Bipolar II disorder and suicidal behavior. Psychiatr Clin North Am 1999;22(3):667–73, ix–x. [17] Ghaemi SN, Hsu DJ, Ko JY, et al. Bipolar spectrum disorder: a pilot study. Psychopathology 2004;37(5):222–6. [18] Judd LL, Akiskal HS. Depressive episodes and symptoms dominate the longitudinal course of bipolar disorder. Curr Psychiatry Rep 2003;5(6):417–8. [19] Judd LL, Schettler PJ, Akiskal HS, et al. Long-term symptomatic status of bipolar I vs. bipolar II disorders. Int J Neuropsychopharmacol 2003;6(2):127–37. [20] Lish JD, Dime-Meenan S, Whybrow PC, et al. The National Depressive and Manicdepressive Association (DMDA) survey of bipolar members. J Affect Disord 1994;31(4): 281–94. [21] Hirschfeld RM, Lewis L, Vornik LA. Perceptions and impact of bipolar disorder: how far have we really come? Results of the National Depressive and Manic-Depressive Association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry 2003;64(2):161–74. [22] Access Economics. Bipolar disorder: costs. An analysis of the burden of bipolar disorder and related suicide in Australia. Melbourne. Available at: http://www.sane.org/images/stories/ information/research/0505_info_bpcosts.pdf. Accessed July 2007. [23] Muzina DJ, Colangelo E, Manning JS, et al. Differentiating bipolar disorder from depression in primary care. Cleve Clin J Med 2007;74(2):89–99. [24] Frye MA, Calabrese JR, Reed ML, et al. Use of health care services among persons who screen positive for bipolar disorder. Psychiatr Serv 2005;56(12):1529–33. [25] Ghaemi SN, Boiman EE, Goodwin FK. Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. J Clin Psychiatry 2000;61(10):804–8, [quiz: 809]. [26] Leverich GS, Altshuler LL, Frye MA, et al. Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine,

BIPOLAR SPECTRUM DISORDER

[27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39]

[40] [41] [42] [43]

[44] [45] [46] [47] [48]

[49]

[50]

549

sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry 2006;163(2): 232–9. Woods SW. The economic burden of bipolar disease. J Clin Psychiatry 2000;61(Suppl 13): 38–41. Begley CE, Annegers JF, Swann AC, et al. The lifetime cost of bipolar disorder in the US: an estimate for new cases in 1998. Pharmacoeconomics 2001;19(5 Pt 1):483–95. Goodwin FK, Jamison KR. Manic-depressive illness: bipolar disorders and recurrent depression. 2nd edition. New York: Oxford University Press Inc; 2007. Guze SB, Robins E. Suicide and primary affective disorders. Br J Psychiatry 1970;117(539): 437–9. Dutta R, Boydell J, Kennedy N, et al. Suicide and other causes of mortality in bipolar disorder: a longitudinal study. Psychol Med 2007;37(6):839–47. Willour VL, Zandi PP, Badner JA, et al. Attempted suicide in bipolar disorder pedigrees: evidence for linkage to 2p12. Biol Psychiatry 2007;61(5):725–7. Valtonen HM, Suominen K, Mantere O, et al. Suicidal behaviour during different phases of bipolar disorder. J Affect Disord 2007;97(1–3):101–7. Muzina DJ. What physicians can do to prevent suicide. Cleve Clin J Med 2004;71(3):242–50. Rihmer Z. Suicide risk in mood disorders. Curr Opin Psychiatry 2007;20(1):17–22. Manning JS, Haykal RF, Akiskal HS. The role of bipolarity in depression in the family practice setting. Psychiatr Clin North Am 1999;22(3):689–703, x. Das AK, Olfson M, Gameroff MJ. Screening for bipolar disorder in a primary care practice. JAMA 2005;293:956–63. Ettinger AB, Reed ML, Goldberg JF, et al. Prevalence of bipolar symptoms in epilepsy vs other chronic health disorders. Neurology 2005;65(4):535–40. Parrisbalogun-Cole S, Wilke W, Muzina DJ. Screening for bipolar disorder in fibromyalgia clinic. Paper presented at the 7th International Conference on Bipolar Disorder. Pittsburgh (PA), June 7–9, 2007. Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 2007;356(17):1711–22. Amador XF, Flaum M, Andreasen NC, et al. Awareness of illness in schizophrenia and schizoaffective and mood disorders. Arch Gen Psychiatry 1994;51(10):826–36. Keitner GI, Solomon DA, Ryan CE, et al. Prodromal and residual symptoms in bipolar I disorder. Compr Psychiatry 1996;37(5):362–7. Hirschfeld RM, Williams JB, Spitzer RL, et al. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry 2000;157(11):1873–5. Wagner KD, Hirschfeld RM, Emslie GJ, et al. Validation of the Mood Disorder Questionnaire for bipolar disorders in adolescents. J Clin Psychiatry 2006;67(5):827–30. Ghaemi SN, Miller CJ, Berv DA, et al. Sensitivity and specificity of a new bipolar spectrum diagnostic scale. J Affect Disord 2005;84(2–3):273–7. Weissman MM, Bland RC, Canino GJ, et al. Cross-national epidemiology of major depression and bipolar disorder. JAMA 1996;276(4):293–9. Joyce PR, Doughty CJ, Wells JE, et al. Affective disorders in the first-degree relatives of bipolar probands: results from the South Island Bipolar Study. Compr Psychiatry 2004;45(3):168–74. McIntyre RS, Konarski JZ, Soczynska JK, et al. Medical comorbidity in bipolar disorder: implications for functional outcomes and health service utilization. Psychiatr Serv 2006; 57(8):1140–4. McIntyre RS, Konarski JZ, Wilkins K, et al. The prevalence and impact of migraine headache in bipolar disorder: results from the Canadian Community Health Survey. Headache 2006;46(6):973–82. Hantouche EG, Akiskal HS. Bipolar II vs. unipolar depression: psychopathologic differentiation by dimensional measures. J Affect Disord 2005;84(2–3):127–32.

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[51] Suppes T, Dennehy EB, Hirschfeld RM, et al. The Texas implementation of medication algorithms: update to the algorithms for treatment of bipolar I disorder. J Clin Psychiatry 2005;66(7):870–86. [52] Yatham LN, Kennedy SH, O’Donovan C, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: consensus and controversies. Bipolar Disord 2005;7(Suppl 3):5–69. [53] Rosa AR, Marco M, Fachel JM, et al. Correlation between drug treatment adherence and lithium treatment attitudes and knowledge by bipolar patients. Prog Neuropsychopharmacol Biol Psychiatry 2007;31(1):217–24. [54] Laborit H, Huguenard P, Alluaume R. [A new vegetative stabilizer; 4560 R.P.]. Presse Med 1952;60(10):206–8 [in French]. [55] Litchfield HR. Aminophenylpyridone, a new mood-stabilizing drug. Arch Pediatr 1960;77: 133–7. [56] Bauer MS, Mitchner L. What is a ‘‘mood stabilizer’’? An evidence-based response. Am J Psychiatry 2004;161(1):3–18. [57] Hirschfeld RM, Bowden CL, Gitlin MJ, et al. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002;159:1–50. [58] Sachs GS. Bipolar disorder clinic synthesis: where does the evidence lead? Focus 2007;V(1): 1–11. [59] Ghaemi SN, Thase ME. Role of antiepileptics and atypical antipsychoticsdbipolar depression. Current Psychiatry 2002;1:13–20. [60] Calabrese JR, Bowden CL, Sachs GS, et al. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. J Clin Psychiatry 1999; 60(2):79–88. [61] Prien RF, Kupfer DJ, Mansky PA, et al. Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders. Report of the NIMH Collaborative Study Group comparing lithium carbonate, imipramine, and a lithium carbonate-imipramine combination. Arch Gen Psychiatry 1984;41(11):1096–104. [62] Perlis RH, Welge JA, Vornik LA, et al. Atypical antipsychotics in the treatment of mania: a meta-analysis of randomized, placebo-controlled trials. J Clin Psychiatry 2006;67(4): 509–16. [63] Kemp DE, Gilmer WS, Fleck J, et al. Aripiprazole augmentation in treatment-resistant bipolar depression: early response and development of akathisia. Prog Neuropsychopharmacol Biol Psychiatry 2007;31(2):574–7. [64] McElroy SL, Suppes T, Frye MA, et al. Open-label aripiprazole in the treatment of acute bipolar depression: a prospective pilot trial. J Affect Disord 2007;101(1–3):275–81. [65] Sokolski KN. Adjunctive aripiprazole in bipolar I depression. Ann Pharmacother 2007; 41(1):35–40. [66] Post RM, Uhde TW, Putnam FW, et al. Kindling and carbamazepine in affective illness. J Nerv Ment Dis 1982;170(12):717–31. [67] Muzina DJ, Elhaj O, Gajwani P, et al. Lamotrigine and antiepileptic drugs as mood stabilizers in bipolar disorder. Acta Psychiatr Scand Suppl 2005;(426):21–8. [68] Muzina DJ, Gajwani P, Kemp DE, et al. Antiepileptic drugs for acute bipolar depression: applying data to clinical practice. Psychiatr Ann 2006;36(9):637–44. [69] Calabrese JR, Sullivan JR, Bowden CL, et al. Rash in multicenter trials of lamotrigine in mood disorders: clinical relevance and management. J Clin Psychiatry 2002;63(11):1012–9.

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Efficient Counseling Techniques for the Primary Care Physician H. Russell Searight, PhD, MPH Department of Psychology, Lake Superior State University, 650 West Easterday Avenue, Sault Sainte Marie, MI 49783, USA

Rationale for counseling by the primary care physician The hidden mental health system The general public and many mental health professionals are unaware that the primary care sector has become the United States’ de facto mental health system [1]. Primary care physicians provide much, if not the majority, of mental health care in the United States [2]. Overall, at least half of all professional visits for mental health are with primary care physicians. Up to 80% of prescriptions for psychotropic medicationsdparticularly antidepressants and anxiolyticsdare written by non-psychiatrists, with the majority written by family physicians, pediatricians, and internists [3,4]. Basic counseling procedures such as empathic listening and collaborative problem solving, as well as using medical data as a motivator for behavior change, are used by many primary care physicians [5,6]. Trends in both the general medical and mental health sectors suggest that primary care patients and their providers would benefit from physicians who can provide mental health counseling as well as targeted behavioral intervention. The role of psychiatric distress in physical symptoms During the 1990s, managed care plans noted that small groups of patients consistently used higher than average levels of health care services. Several studies found that 10% or fewer of the patients in a particular panel used up to 30% of a health care plan’s resources [7]. Patients who had psychological conditions used significantly more medical services for physical health conditions than those without mental health problems [8]. In examining patient panel characteristics, up to 50% of high utilizers had comorbid mental

E-mail address: [email protected] 0095-4543/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pop.2007.05.012 primarycare.theclinics.com

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health conditions [8,9]. Previous research has found that providing behavioral health services reduces use of medical resources by 20% to 40%, primarily though reductions in emergency department and office visits by high utilizers [10–12]. The most common symptoms presenting in the average primary care office usually cannot be attributable to a specific organic cause. During a 3-year period, of the 10 most common presenting complaints in primary care (ie, chest pain, fatigue, dizziness, headache, edema, back pain, dyspnea, insomnia, numbness, and abdominal pain), fewer than 15% had a specific cause, suggesting a significant role for psychosocial factors [13]. For example, the key factors distinguishing treatment- from non–treatment-seeking patients who have irritable bowel syndrome are anxiety and depression and a fear of having cancer [14]. Overall, the service use data reviewed suggests much of primary care focuses on management of psychiatric conditions, albeit in the context of physical symptoms. Prevention and lifestyle modification Other groups of patients who have disproportionate health care costs have lifestyle risk factors such as smoking, excess alcohol use, high-fat diets, and a sedentary lifestyle. Multiple studies indicate that habit change is very difficult to maintain [15]; however, because these health risk behaviors are also significant etiological factors in cardiovascular, endocrine, and respiratory disease, physicians attempt to counsel patients to change these long-standing habits. Historically, the most common counseling method employed has been education about the long-term health risks of continued smoking, drinking, and so on. Physicians often report feeling that their efforts have been ineffective with these problems [16]. Obstacles to mental health care Although the need for mental health services among primary care patients is high, there are several obstacles to effective service delivery. First, mental health services are often ‘‘carved out’’ from medical insurance plans, and are subject to their own review and certification processes. In some regions of the country, primary care physicians are not reimbursed for providing psychiatric treatment because they are not recognized mental health professionals. Even when a mental health referral is successfully made, follow-through is often problematic. A high percentage of patients, ranging from 25% to 50%, do not keep the initial appointment [4,17]. Patients may be concerned about the stigma of seeing a ‘‘shrink,’’ or may be offended by the belief that that their doctor sees the patient’s somatic complaints as being ‘‘all in their head.’’ (ie, ‘‘Dr. Searight, I don’t know why Dr. Jones sent me to you. I’m not psycho. It’s my back that’s hurting; I think I’ve got a slipped disk. There’s nothing wrong with my mind!’’)

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Physicians themselves often say that although they would like to do more counseling with their patients, they simply do not have enough time. The average ambulatory primary care office visit is 13 minutes in duration [4,18], and often involves multiple complaints involving several bodily systems. A common physician fear is that asking the patient some personal questions about his life and possible sources of distress will open a ‘‘Pandora’s box.’’ The physician will find herself with an emotionally distressed patient who is sobbing hysterically and sharing intimate, painful parts of his life while the physician becomes overwhelmed, has no idea what do next, and falls further behind in her schedule. Even among physicians who have had training in psychotherapy, the models learned during psychiatry or behavioral medicine rotations in medical school or residency are far too time-consuming for a busy 40-patientsper-day practice. A key challenge is adapting psychotherapeutic techniques to the time-sensitive, multiproblem primary care context. This article describes four approaches to counseling specifically developed or adapted for primary care that are sensitive to the time limitations of this setting: the BATHE technique, the FRAMES brief intervention model, an adaptation of the Transtheoretical Model (Stages of Change), and a brief version of Motivational Interviewing. These models are brief, problem-focused, and structured. They can be organized as protocols. Although the BATHE technique is useful for broad-based psychosocial issues, all four approaches overlap to some degree, and may be applied to altering health risk behavior. The BATHE technique BATHE, an approach to counseling patients on psychosocial issues, was developed by a psychologist and family physician specifically for the primary care setting. BATHE is an acronym for a sequence that the physician moves through addressing specific areas that build on each other: B, background; A, affect; T, troubles; H, handling; and E, empathy [19,20]. Stuart and Lieberman developed BATHE in a protocol format, making it compatible with how physicians are often trained in new techniques. BATHE is described in detail in The Fifteen Minute Hour: Applied Psychotherapy for the Primary Care Physician [20]. Actually, the author of this article and several of his physician colleagues have found that with many patients, a BATHE interview often requires less than 5 minutes with some patients, and with others, a minute or less. Although Stuart and Lieberman suggest that the technique be used with all patients, many physicians reserve BATHE for conditions in which psychosocial conflict is a likely contributor, such as tension headaches or recurrent abdominal pain in children. BATHE is an initial screen for anxiety, mood, and adjustment disorders. Table 1 lists the questions for each of the BATHE dimensions.

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Table 1 The BATHE interview Dimension

Question or statement

Purpose

Background

‘‘What’s going on in your life?’’

Affect

‘‘How do you feel about it?’’

Troubles

‘‘What (troubles) bothers you the most about the situation?’’

Handling

‘‘How are you coping with (handling) the situation?’’ ‘‘It sounds very difficult, frustrating, etc.’’

Elicit recent psychosocial history, including stressors Elicit type and intensity of patient’s emotional reaction Target a specific aspect of the problem; makes problem manageable Assess patient’s coping skills

Empathy

Provide emotional support

The BATHE interview was developed by Drs. Marian Stuart and Joseph Lieberman. Data from Stuart MR, Lieberman JA. The fifteen minute hour: applied psychotherapy for the primary care physician. 2nd edition. Westport (CT): Praeger; 1993, and Stuart MR, Lieberman JA. The fifteen minute hour: practical therapeutic interventions in primary care. 3rd edition. Philadelphia: Saunders; 2002.

For the physician on a tight schedule, a problem’s background may be the most daunting part of the protocol. Physicians’ reluctance to engage in counseling stems in part from fear that patients will need extended time to relate the details and will become emotionally distraught, only adding more time to the encounter. The clinicians may not feel that they can adequately understand the problem without delving at length into the patient’s background. By following several principles, physicians can prevent the background segment from becoming time-consuming. There are several misconceptions about understanding the details of a patient’s problem. First, a common myth is that the more the patient talks about the problem, the better able the clinician will be to understand and help. Actually, although a certain level of important detail is necessary, there rapidly comes a point of diminishing returns in the value of further background information. Signs that the exchange is becoming unproductive will include: preoccupation with nonessential detail, repeatedly externalizing the source of difficulty (‘‘Like I’ve been telling you, if my boss would just treat me fairly, I’d be fine.’’), and continuing to verbally rehearse the same problem details. Once this pattern is apparent, the physician can structure the exchange through several strategies. The physician can summarize the problem (‘‘I hear that you’re really worried because you found a bag of marijuana in your son’s jacket. You don’t want to turn him over to the police, but you do want him to know that he could get in serious trouble if he keeps on this road.’’), gently interrupt, and refocus the ruminative patient (‘‘I think I’ve got a handle on the problem and why it is so important to you.’’). This refocusing should be followed by moving ahead to the next question (affect), to maintain targeted progression.

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Frequently, the patient (and often, the clinician) becomes overwhelmed with the escalating details of the problem. The patient’s initial anger about a supervisor at work, with continued encouragement for more detail, can rapidly expand to encompass harassing coworkers, a critical, unsupportive spouse, and children who are failing in school. In contrast to the psychotherapist’s frequent request to ‘‘Tell me more about it,’’ the physician seeks to keep the problem time-focused and manageable. This limited focus, itself, is actually therapeutic, because the problem’s repeated, detailed verbal recitation may actually represent part of the patient’s poor coping skills. Repeated problem rehearsal only increases the emotional intensity and the complexity of the issue. Asking the patient how he feels (affect) appears straightforward; however, many patients will remain ‘‘bogged down’’ in factual details. It is actually a disservice to the patient to remain embroiled in his overly elaborated narrative about ‘‘who did what to whom’’ [20]. For patients who continue to remain overfocused on details, the physician may have to ask the question again with greater emphasis (eg, ‘‘I think I have a good handle on the difficulty you’re having with your son.but how do you feel about it?’’). Some patients, such as those who tend to somatize psychological distress, may have difficulty describing their emotions. Other patients, coping with a crisis through denial, may have little access to their affective life. The physician can help these emotionally restricted patients express themselves by suggesting some affective adjectives reflecting common reactions and asking the patient if any of them ring true. For a patient whose wife has suddenly left him after a 10-year marriage, terms such as ‘‘angry, hurt, lonely, overwhelmed, abandoned, sad,’’ and so forth, might be suggested to the patient. In the case of the recent death of a parent, words such as ‘‘ emotionally painful, devastated, or lost’’ might fit.) With patients who have difficulty verbalizing feelings, the physician may be able to infer their emotional state through body language (physician, noting the patient’s facial; grimace and clenched fists: ‘‘It looks to me like you may be pretty angry with the custody arrangement with your ex-wife.’’). Focusing the patient on the most troubling aspect of the situation makes the problem manageable. Several guidelines are useful in determining what is troubling the patient most about the situation. A common objection to this approach is that it may seem to reduce a major life event, such as the death of a parent, to an artificially narrow and almost trivial issue; however, the physician should appreciate that it is easy for both the patient and the provider to become overwhelmed by the magnitude of complicated psychosocial problems. This experience of ‘‘it’s just too much’’ may leave both parties stuck in a state of emotional paralysis. Asking the patient to focus on a key, specific aspect also helps him prioritize conflicting demands. The interviewer may feel awkward asking a patient, ‘‘What troubles you the most about your mother’s sudden death?’’, and assume that she knows what most is distressing to the patient. These

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assumptions are often proven wrong., however. For example, a 51-year-old woman presented in the office with a recurrence of irritable bowel symptoms. From the background, the physician learns that the patient’s mother died 2 weeks ago, and that although the patient feels sad, there is also some relief, because her mother had terminal cancer and had been in pain for many months. Responding to the physician’s ‘‘What is troubling you the most about her death?’’ the patient, rather than saying ‘‘I will really miss mom’s love and support,’’ instead, anxiously blurts out: ‘‘I don’t know what we’re going to do about my little sister. She’s 37 and she’s been in and out of jail, halfway houses, and drug treatment. Mom always helped her out. She would always bail my sister out of jail and gave her a place to stay. No one else in the family will do that.’’ This response clearly directs the physician to assist the patient in examining how she and other family members may respond to her sister’s crises in the near future. Although patients may initially hesitate and have to think for a minute, nearly everyone can label a problem’s most troubling aspect. By asking patients how they are handling a stressor, physicians can quickly assess coping skills. Additionally, the patient can be asked about possible actions she may take and the likely consequences of those actions [19,20]. For a young woman just learning that she tested positive for gonorrhea, her immediate response might be, ‘‘I’m gonna kill my boyfriend.’’ Physician: ‘‘What would happen then?’’ Patient: : ‘‘Besides him being dead, I’d probably have to go to jail.’’ A useful question for assisting the patient in evaluating her solution is: ‘‘What’s the worst thing that could happen if you carried that out?’’ At this point, the physician may encourage the patient to consider possibilities and their consequences on her own, while leaving further discussion until the next appointment. Other focused strategies include asking the patient what she has done to get through difficult times in the past, framing some options for her (physician: ‘‘It sounds like this supervisor isn’t going away. At this point, I hear several options for the stress at work: quitting the job, requesting a transfer to another department, trying to talk with the supervisor directlydmaybe with the union rep present, or just trying to stick out the situation for 3 more years until you can retire.’’). In laying out these possibilities, the physician should avoid directing the patient to any specific one. The physician is unlikely to know all of the subtle variables involved, and responsibility should remain with the patient. Particularly if the patient is planning on setting a limit (eg, not returning to an abusive partner), her social network should be surveyed. The patient should be encouraged to consider which relationships are genuinely supportive, and the physician should respond to the patient in terms of what is genuinely in the patient’s best interests rather than those of family and friends who frequently have their own needs for the patient to remain unchanged. Increased alcohol or cigarette use or overeating suggests poor coping skills. With patients who are concerned about ineffective lifestyle habits or

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who are not ready to make major lifestyle changes (eg, leaving an abusive spouse), the physician can unbalance patients’ stable views of their inefficacy by adding the word ‘‘yet’’ to their reflective statements. Patient: ‘‘I know I’d have more energy to cope with my husband’s illness if I could just exercise but I can’t do it.’’ Physician: ‘‘You haven’t started your exercise program yet.’’ The term ‘‘yet’’ conveys optimism about the future, changes the ‘‘traitlike’’ permanence of their inability to change behavior [20], and implies patient self efficacy. Patients may frequently present their difficulty as including an imminent decision needing to be made. When in crisis and emotionally labile, patients often experience urgency to make decisions immediately. Even though the emotional arousal precludes optimal reasoning and information is often incomplete, patients feel that their distress may be rapidly alleviated once they decide and embark upon a specific course of action. The physician should counter this urgency by encouraging some stopgap coping measuresdstaying with a relativedand returning for a follow-up soon. The ‘‘tincture of time’’ [19] alone is likely to reduce the intensity, so that decision-making can occur in a more realistic, thoughtful manner. This principle reflects the saying, ‘‘Time heals all wounds,’’ and refers to the experience that the passage of time tends to make problems seem less emotionally intense. In some cases, such as patients who have become socially isolated or physically inactive, the physician may attempt to contract with the patient. For example, the patient who has become socially isolated will agree to contact at least two acquaintances by phone before the next office visit. Increased physical activity is particularly helpful for patients who have major depressive disorder, and has been found to be associated with improved mood [19,20]. Conveying empathy is fairly straightforward. By communicating that she understands the patient’s emotional difficulty, the physician provides support and validates the patient’s experience. An empathic statement (‘‘It sounds like it’s frightening, but would also be a relief to move out on your own.’’) communicates closure to the counseling session [20]. FRAMES As indicated in Table 2, FRAMES is a protocol originally developed to address objective health risk behavior such as alcohol abuse [5,6]; however, it can be readily adapted to problems such as smoking and nonadherence with chronic disease management regimens. In using FRAMES (Feedback, Responsibility, Advice, Menu of strategies, Empathy, Self-efficacy), the physician begins with objective feedback regarding personal risk. Although a score on the CAGE (alcohol use) or brief Fagerstrom (nicotine use) may be used, ‘‘hard’’ physiological data are preferred. For alcohol, liver function tests or blood pressure readings may be useful; for smokers, the number of upper respiratory infections in

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Table 2 The FRAMES model for health risk behavior counseling Dimension

Physician action or statement

Purpose

Feedback of personal risk

Explanation of relationship between health risk behavior and abnormal laboratory test results, physical examination abnormalities, or self-report questionnaire scores ‘‘You have the ultimate control over your drinking, smoking, etc.’’ ‘‘For your health, I strongly recommend that you cut down on your drinking/stop smoking.’’ Pharmacotherapies; avoiding high risk situations; encouraging alternate behaviors; changing environmental antecedents

Provide factual, objective basis for risk reduction counseling

Responsibility of patient Advice to change

Menu of strategies

Empathetic style

Promote selfefficacy

‘‘Quitting smoking is a real challenge.’’; ‘‘It sounds like you recognize that those first few days are the toughest.’’ ‘‘You sound like you have a solid plan to cut down on your drinking. Your health and family seem to be very important, and you’re determined to be successful.’’

Emphasize that decision for change must come from patient, not physician Authoritative, clearly stated ‘‘prescription’’ for behavior change Emphasize patient choice and responsibility for change process; selects individualized strategies most likely to be successful Provide emotional support

Communicate confidence in patient’s ability to change. Remind patient of her personal reasons for change.

Data from National Institute on Alcohol Abuse and Alcoholism. Brief intervention for alcohol problems. Alcohol Alert 1999;43;1–4.

the past year; for Type II diabetics, hemoglobin A1C and the presence of any early-stage complications such as microalbumineria. As with most forms of brief counseling, responsibility for change rests with the patient. This position is underscored with physician statements such as, ‘‘No one can make you change. What you decide to do about your drinking is up to you.’’ Some patients, however, may experience these assertions as condescending or confrontational. A more productive alternative that maintains patient responsibility might be, ‘‘What are your thoughts about how to get your blood pressure under better control?’’ The physician then advises the patient directly to alter his behavior (‘‘I strongly recommend that you cut down on your drinking/stop smoking’’) [5]. In keeping with the emphasis on patient responsibility and the view that patients know what works best for them, the physician does not prescribe a specific method for changing health risk behavior. Instead, physicians provide a ‘‘menu’’ of strategies, and encourage patients to select the techniques most consistent with their own values and lifestyle. For patients who have

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alcohol abuse (not alcohol dependence), strategies might include: watering down drinks, allowing a longer period of time to elapse between drinks, sipping slowly rather than drinking, and maintaining a written record of drinking and nondrinking days [5,6]. FRAMES draws upon Motivational Interviewing (discussed later in this article) research indicating better patient outcomes when physicians were empathic, nonjudgmental, and accepting rather than confrontational [5,6]. This acceptance should extend to the patient’s internal struggles with cravings and emotional triggers for substance use [21]. When addressing health risk behaviors, physicians should consider and frequently ask patients about the needs being met through drinking, smoking or overeating [22]. There are several common themes that arise: tension reduction, sociability (particularly when valued others engage in the behavior), and self-nurturance when feeling lonely. When asking patients about these issues, the physician should combine healthy curiosity with concern. This supportive, noncoercive stance (‘‘It sounds like drinking helps you relax after work. That ‘down time’ in the bar before you go home sounds important.’’) along with direct statements to the patient (‘‘You sound very determined to stop smoking because of your responsibility to be a healthy model to your son.’’), enhances their self-efficacy or belief in their ability to alter these long-standing habits. Physicians may ask about previous efforts to stop the behavior of concern (eg, smoking), or encourage the patient to reflect upon other life challenges that the patient has overcome, such as the ability to cope with a particularly difficult divorce. By highlighting these successes, the physician is emphasizing a patient’s existing strengths as a foundation for future change. For example, with a smoker who previously quit for a month, the physician can emphasize that the patient made it through the ‘‘tough’’ nicotine withdrawal period. Enhancing patient self-efficacy requires the physician to communicate a balance between optimism and realism. Physicians frequently need to counsel patients about realistic goals. Setting unattainable goals leads to patients’ sense of failure, diminished self-efficacy, and greater reluctance to attempt future habit changes. Patients’ weight loss goals, in particular, are often very unrealisticda factor likely contributing to ‘‘yo-yo dieting.’’ Foster and colleagues [23] asked 60 obese women entering a weight loss program to list the weight loss necessary to attain their ‘‘dream weight’’ (38% loss), ‘‘happy weight’’ (31.4%), ‘‘acceptable weight’’ (25.1%), and ‘‘disappointed weight’’ (17.4%). After a 48-week treatment program, nearly half of the women did not even lose their ‘‘disappointed weight,’’ although this group averaged about a 16 kg loss. As this study illustrates, physicians should always inquire about patient’s goals and negotiate end points likely to be achievable. Patients are often given written self-help materials. Additionally, a nurse from the practice may contact the patient for brief follow-up and to determine if he should return for further counseling visits [5,6].

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Stages of change (transtheoretical model) Although perhaps difficult to currently appreciate, changes in health risk behaviors were previously conceptualized as solitary events rather than as processes; a patient quit smoking, drinking, or initiated regular exercise on a particular day [24]. With much of the initial work done in smoking cessation, it became apparent that quitting was a complex process over time, with varying degrees of patient motivation. Although there is some variability in the number of processes involved, the basic stages of change are outlined in Table 3. For the physician, understanding a patient’s stage on the continuum is helpful, because the provider can match her message to the patient’s level of readiness for lifestyle change. Precontemplation Patients in this stage are not planning on taking any action on their health risk behavior in the next 6 months. Occasionally, this inaction stems from a lack of information, but more commonly, patients are minimizing the health risks, experience little self-efficacy regarding change, or have made several unsuccessful change attempts and are demoralized [25]. Physicians should avoid the temptation to either give a ‘‘pep’’ talk about successful habit change or lecture about long-term health consequences. Instead, asking about the values surrounding the behavior and the role it plays in the patient’s life (‘‘What do you like about smoking?’’; ‘‘What keeps you drinking every day?’’) or future-oriented questions implying that the patient will eventually change (‘‘How long do you think you’ll keep smoking?’’; ‘‘What would be the first sign that its time to cut down on your drinking?’’) are more likely to engage the patient, while acknowledging the problem. On many occasions, the patient’s presenting problem (upper respiratory infection, gastritis) is directly related to his risk behavior. To optimally exploit these opportunities, the physician may borrow from FRAMES (see above) or Motivational Interviewing (see below), and make a general, factual statement followed by an open-ended question. (eg, ‘‘It looks like you have a respiratory infection. People who smoke get these more frequently, and when smokers get them, the infections tend be more severe. Over time, many smokers develop permanent lung damage, a condition called chronic obstructive pulmonary disease, where they have permanent problems with breathing. [Physician deliberately pauses] What do you think of that?’’). If the patient indicates that he is not ready to change, the physician may respond: ‘‘It sounds like you’re not willing to quit, yet. I’ll check in with you the next time I see you.’’ The physician makes a note in the patient’s chart, and at the next visit, follows up: ‘‘I remember the last time that I saw you that you said it wasn’t a good time to quit smoking, quite yet. How are you feeling about quitting today?’’

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Table 3 Stages of change (transtheoretical model) Stage

Physician counseling techniques

Purpose or goal

Precontemplation

Provide factual statement about health effects of smoking, nonadherence, etc., followed by ‘‘What do you think of that?’’; ‘‘What do you like about smoking?’’; ‘‘What keeps you drinking?’’; ‘‘How long do you think you’ll smoke/drink?’’ Encourage the patient to consider the pros and cons of changing. ‘‘What are the advantages and/ or disadvantages of changing?’’; ‘‘What could get in the way of changing?’’; ‘‘Many patients benefit from [specific suggestion].’’ Ask the patient to set a specific change date. ‘‘Which specific strategies are you planning to use?’’ (patient may need suggestions); ‘‘What would be a high-risk situation (for relapse)?’’; ‘‘How can you prepare for it?’’ Ask about unforeseen obstacles and lapses and how patient managed them. Support patient’s efforts. ‘‘How is the plan working?’’; ‘‘What challenges have come up that you didn’t expect?’’; ‘‘Any lapses?’’ (normalize lapses); If yes, ‘‘How did you get back on track?’’ Praise and support patient. Use lapses and relapses as learning experiences. ‘‘Over the past 6 months, which situations have been the most challenging for you?’’; ‘‘How did you handle the situation?’’; ‘‘Since you have not been smoking/drinking, etc., for 6 months/a year, etc., have there been other changes in your life that you didn’t expect?’’; ‘‘How has your family reacted?’’

Increase patient awareness of behavior; increase patient’s self-consciousness of decision to continue behavior

Contemplation

Preparation

Action

Maintenance

Patient clearly articulates concrete, realistic pros and cons of changing; early reflection on potential obstacles to change; patient made aware of available resources to assist change when ready. Obtain commitment to initiate change. Patient able to describe a repertoire of behavioral strategies to cope successfully with high-risk situations.

Assess effectiveness of behavior change strategies; address unexpected problems; minimize impact of lapses to prevent relapses. Use lapses to learn about unanticipated challenges

Help patient internalize new identity as a non-smoker, non-drinker, etc; fine-tune problem-solving skills for high- risk situations; identify any potential life events that could provoke long-term relapse

Data from Velicer WE, Prochaska JO, Fava JL, et al. Smoking and stress: applications of the transtheoretical model of behavior change. Homeostasis 1998;38:216–33.

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Contemplation In contemplation, change is planned within the next 6 months. Key issues include helping the patient to optimally structure his environment to support behavior change. Over time, long-term patterns of overeating, smoking, and excess alcohol consumption are likely to become conditioned responses to environmental cues. For smokers, relevant stimuli exerting some control are likely to be friends and family members who smoke, and the presence of ashtrays and lighters [26], as well as the smell of smoke in the carpet, upholstery, and drapes. Particularly important at this point is lining up persons who are supportive of the change effort, and identifying those who might sabotage improved health behavior. When a smoker is married, there is a greater likelihood that his spouse is a smoker [27]. A married man may decide to quit after he and his wife find their 13-year-old daughter smoking, because he wants to set a positive example for their child. His wife, on the other hand, experiences little selfconfidence in her ability to quit, feels guilty about her role modeling for her daughter, but expresses her discomfort through angry defiance. She announces to her husband that he is ‘‘on his own’’ in his efforts to quit, and that she will not change her own smoking habits. She will continue to smoke after meals, have ashtrays and lighters throughout the house, and persist in smoking in the car during family outings. By being aware of these obstacles well in advance of the action date, the patient can be proactive in developing a management strategy. For the patient above, attempting smoking cessation, a network of nonsmoking friends or an even a formal support group may help him face the challenges at home. Physicians should also maintain a library of useful patient handouts, including information sheets for the various stages of habit change, selected Web sites (the American Academy of Family Physicians Web site has patient education sheets for many common problems: http://www.aafp.org/ online/en/home.html), and when possible, a list of personally reviewed and approved self-help books. Research indicates that written material is less effective than when it is paired with individualized patient counseling, however [28]. Preparation The patient is now intending to initiate behavioral change in the next month. A concrete plan should be fairly well established. For smoking, the plan should include a specific quit date, with prescribed medication or nicotine replacement in advance if indicated. Counseling should center on asking the patient about potential high-risk situations that he may encounter. For example, upcoming family gatherings with big meals may be particularly challenging for maintaining a 1200 calorie diet. It is important to ask the patient to generate several realistic options for managing these situations. For smoking cessation, even minor

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daily routines, such as having a cup of coffee and a cigarette in the morning, will need to be revised, perhaps by having coffee at the office in a smoke-free building. Kaizen: the principle of small steps If a specific day for initiating the change program is several weeks away, patients can begin making very small steps toward their larger change through a technique called ‘‘Kaizen,’’ Japanese for ‘‘improvement’’ [29]. Although not a formal part of the transtheoretical model, this strategy is often helpful during the preparation and action phases. Kaizen initially arose in industry as a rapid quality improvement strategy. In the United States, the Second World War required rapid increases in industrial productivity; however; there was not time for thoughtful large-scale studies and the development of long-term plans. Each employee, regardless of his role in the factory, was encouraged to constantly look for and implement any small changes that might improve productivity. These small changes would, collectively, lead to major increases in output. A practical primary care example of the Kaizen strategy is increasing activity and energy among patients with chronic fatigue syndrome (CFS). CFS patients are typically caught in a cycle of fatigue and deconditioningdthey are tired, not because they are doing too much (as they often report), but because they are inactive [30]. A common treatment is to place these patients on a limited exercise protocold5 minutes per day for 3 to 5 days per week initially, with the addition of 2 minutes per week [30]. This very minimal initial exercise requirement overcomes patients’ resistance to do ‘‘too much’’ activity that would be exhausting. The patient is likely to go beyond this limit from time to time, and find the increased activity to be tolerable. Even if he does not spontaneously go beyond the limit, by the end of 3 months, he will be walking a half hour per day by following the protocol [30]. Similarly, in the preparation phase for smoking cessation, the patient may be encouraged to smoke one or two fewer cigarettes per day, or simply to inhale less. For the completely sedentary patient, encouraging 1 or 2 minutes of brisk walking in place while watching television could be an initial effort. A small dietary change might be to throw away the first bite of food [29], or put slightly less cream or sugar in one’s coffee. For patients consuming a large number of caffeinated sodas each day, to the point that they are experiencing anxiety and insomnia, a multiweek Kaizen strategy is helpful. Patients are instructed to purchase a small amount of the non-caffeinated form of the soda, and for the first week, only pour enough into the glass to fill it to a 1⁄4 to 1⁄2 in level. Then, they are to fill the rest of the glass with the regular (caffeinated) soda. Each week, patients are to add a little more decaffeinated soda to each drink, until eventually they are drinking completely non-caffeinated soda. The same

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strategy can be used to reduce calorie intake by having patients add small amounts of sugar-free soda to their regular beverage. Although these changes may appear so small that they could have absolutely no benefit, this technique of small steps confers several psychological advantages. First, small changes provide the patient with a modest experience of self-efficacy, subsequently making larger challenges less formidable. For patients who have low initial levels of self-efficacy, early successes are particularly important. The ‘‘ bar’’ needs to be set low enough that the patient will be able to perform early assigned tasks. Kaizen addresses the difficulty that patients have making transformative changes for which they experience little self-efficacy. As a result, patients do not make the first step toward habit change, or if they do, failure occurs relatively soon, with consequent lowered expectations for trying again. Maurer [29] suggests that patients make initial small changes to bypass the fear and anxiety that the challenge of major lifestyle transformation is likely to provoke. Second, an underlying theme in any type of habit change is a sense of being controlled by the unhealthy behavior rather than having control over one’s life. These small steps toward health are under the patient’s control and challenge his belief in helplessness. Finally, its not uncommon for patient’s small steps to gradually become bigger ones on their owndwhile exercising, the patient becomes engrossed in the TV show and ends up walking in place for 15 minutes instead of 5 [29]. Action Specific behavioral changes have occurred within the past 6 months and are ongoing. Physicians, experiencing encounters with patients in this phase as rewarding, may wonder if they can contribute anything further to the patient’s ongoing success. The physician may serve as an external ‘‘monitor,’’ a respected authority that the patient can ‘‘check in’’ with to report and validate behavior change. This role may be particularly important when the patient’s social context is unsupportive or ambivalent about the habit change. Additionally, ambivalence about change is likely to periodically crop up [31]. Spouses, romantic partners, or friends may feel threatened by the patient’s greater sense of self control, and in turn, fuel doubts about the desirability or the patient’s capacity for enduring change. There are also likely to be other obstacles that only emerge with time and that require a plan. Maintenance, lapse, and relapse In the maintenance stage, patients have successfully maintained their change for more than 6 months. In addition to being praised for their success, patients should be asked to describe their strategies and skills for success. Many patients will initially respond that they don’t really know how they are succeeding, stating that, ‘‘Its just happening.’’ By being encouraged to articulate their coping mechanisms, the patient will experience greater

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control over these skills, and be able to apply these strategies across more situations. Although less frequent, they are still likely to encounter novel, unpredictable challenges. Lapses, relapses, and recycling through the stages are probably more the rule than the exception. For example, the average smoker makes about six quit attempts before permanent cessation [32]. In anticipating lapses, the physician should prepare the patient without communicating pessimism about the likelihood of success: ‘‘Smoking has been a big part of your life for many years. After you’ve quit for a few weeks, you may find yourself smokingdmaybe without even thinking about it. This happens to most people who quit smoking. They find themselves in situations that they hadn’t expected, such as an office party at a bar where a lot of people are smoking. The important part is to be aware of what you’re doing and stop as soon as you can. Ten puffs is better than 20; 5 cigarettes are better than 10. After you’ve caught yourself, it’s a good idea to look at the situation and see if you have any ideas about things that may have contributed to your lapse so that you can learn from it. You probably either thought you had enough control to be able to manage a situation with a lot of smokers or just hadn’t planned ahead for how challenging the situation would be. These lapses are times to learn more about your smoking triggers.’’ When patients return to the physician reporting a lapse or even that they have relapsed and returned to their previous habit, the physician’s response is critical. The former two packs per day smoker who has been abstinent for 7 months but returned to smoking 5 to 10 cigarettes per day a week ago can often, with focused problem solving, return to abstinence without regressing to the previous intake. Many patients, however, are reluctant to seek help from or return to the physician because of a sense of failure and the experience of having ‘‘let the doctor down.’’ The lapsed smoker, drinker, or dieter often anticipates that her physician will be angry with her. When patients in the midst of a lapse return to the clinic, it is crucial that the physician be accepting, understanding, and nonjudgmental. As noted above. lapses are learning experiences; however, lapse may often trigger a cognitive process called catastrophization, in which the patient tells himself that he’s lost all self-control (‘‘Oh, I ate four pieces of fried chicken. I’ve already blown it. I might as well have the chocolate cake and ice cream, too.’’). By pointing out this automatic thought process, the physician can suggest to patients that when they do lapse, they ‘‘try to give in less’’ each time. The interview should be a collaborative exploration of the circumstances contributing to the lapse. There were evidently some unanticipated environmental or interpersonal dynamics that caught the patient off guard and triggered the lapse. The focus should be on identifying these issues and developing a strategy for managing them in the future as well as ‘‘getting back on the wagon.’’ Similar strategies should be employed with patients who relapse. With smokers considering another quit attempt, it is helpful to inquire about

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the length of previous cessation episodes. Episodes of multiple weeks can be used to bolster patient self-efficacy about future quit attempts. Asking the patient about factors contributing to relapse will assist in developing future behavioral coping strategies. Particularly after a successful period of maintaining behavioral change for a year or more, at the next change attempt, the patient may go directly to the action phase.

Motivational interviewing Motivational Interviewing (MI) is a quasi-Socratic style of questioning that gives a predominant role to patients’ ambivalence about personal change (Table 4) [33,34]. MI was developed for treating substance abusers [33], and is a counterpoint to the highly confrontational style characteristic of the field for many years. The physician practicing MI has four basic tasks: (1) quickly develop an empathic, supportive collaboration with the patient; (2) highlight a discrepancy between the patient’s health risk behavior and another strong, personal value; (3) avoid arguing, cajoling, or lecturing the patientdparticularly when he seems to be resisting change; and (4) focus on the patient’s strengths, and support the patient’s efforts to change [33]. Adopting a collaborative, empathic stance, the physician puts herself on the ‘‘same side of the fence’’ with the patient rather than in opposition [34]. By communicating that ambivalence about change is normal, and that she is Table 4 Key components of motivational interviewing Principle

Physician action

Purpose

Express empathy

Convey understanding that habit change is difficult and that ambivalence about change is normal; find ‘‘common ground’’ with patient Elicit patient’s important values; through questioning, gently highlight inconsistency between core values and health risk behavior Regard resistance as a signal to approach the patient differently; do not argue with patient Support patient’s belief that he can change; remind patient of any previous successful changes

Develop supportive relationship; assure patient that physician will not be critical; patient will be more receptive to selfexamination Primary change mechanism; patient must resolve dissonancedhopefully, by recognizing that he should change health risk behavior Emphasize patient responsibility for change; prevent arguments that detract from key issues Enhance patient confidence; may be able to apply skills from previous success to current behavior change

Develop discrepancy

Roll with resistance Support selfefficacy

Data from Miller WR, Rollnick S. What is motivational interviewing? In: Miller WR, Rollnick S, editors. Motivational interviewing: preparing people for change. 2nd edition. New York: Guilford; 2002. p. 33–42, and Emmons KM, Rollnick S. Motivational interviewing in health care settings: opportunities and limitations. Am J Prev Med 2001;20:68–74.

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interested in what the patient sees as important, the partnership is strengthened further and the patient’s fear of criticism is allayed. In a traditional psychotherapeutic context, MI actually avoids early attention to the health risk behavior, but instead focuses on the patient’s own concerns. Typically, the problem with addiction, adherence, and so on, will arise during this discussion, often as a factor that is creating a barrier in some part of the patient’s life (eg, relationships, work, and pursuit of hobbies). In the primary care context, the physician will, of necessity, have to focus on the health risk issue at hand fairly quickly. If, however, a link can be made between something that is important to the patient and the behavior of concern, this association will provoke cognitive dissonance. When the physician is not sure about the patient’s core values, she can ask: ‘‘What is most important to you?’’ A common response is a family member or members. For example, a 62-year-old, two packs a day smoker complains of not being able to keep up with his grandchildren because he becomes short of breath. This valued relationship would likely be useful in developing discrepancy. Similarly, in prenatal care, a key motivator for change would be to emphasize the inconsistency between the patient’s behavior (drinking alcohol while pregnant) and her core values (‘‘I am a caring mother who would never harm my baby.’’). Along the way, the patient may resist the forces of change. Rather than prodding, arguing, or confronting the patient, physicians should view resistance as merely the other side of normal ambivalence about change, and see it as a signal to find a different way to collaborate. Throughout the exchange, the physician must convey an attitude of confidence in the patient’s ability to change [33]. Because the arguments for actually making the behavior change and the personal responsibility for change are generated by the patient rather than the physician, self-efficacy is enhanced. In medical settings, MI, similar to the FRAMES model, may include presenting health risk information to the patient. This information is presented to the patient in an emotionally neutral, factual manner (eg, ‘‘Your blood pressure is high. We know that people who have high blood pressure over periods of time are much more likely to have strokes and heart attacks. Drinking heavily is one thing that can cause high blood pressure.’’). In MI, after a brief pause, the physician follows with an open ended query (‘‘What do you think of that?’’), giving responsibility back to the patient. MI has been significantly streamlined into 5- and 10-minute versions for the primary care setting [35]. For example, in smoking cessation, patients now have the choice of nicotine replacement therapy as well as two non-nicotine pharmacotherapies. Explicitly stating these choices further communicates that the patient is responsible for the behavior change. Modified MI does have some research support, albeit limited. Brief, onetime MI was found to be more effective than direct advice for smoking cessation. At follow-up, MI recipients were more likely to have abstained in the past 24 hours, delayed their first cigarette of the day beyond 5 minutes, and

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quit for at least 1 week. Of interest, MI’s advantage was more pronounced among patients in the precontemplation stage [36].

Summary Many patients expect mental health treatment from their primary care physician. Although intensive, in-depth, weekly psychotherapy is beyond the scope of family medicine, most medical patients expect any counseling to be time-limited and problem-focused rather than extended and oriented toward personal growth. Although patients who have severe mood disorders, psychoses, and personality disorders should be referred to the specialty mental health sector, primary care physicians can effectively manage the majority of patients who have mild to moderate major depressive or anxiety disorders. The addition of brief counseling is likely to increase adherence with prescribed psychotropic medications. Much of day-to-day practice involves managing conditions in which unhealthy lifestyles play a major role. FRAMES, Stages of Change, and Motivational Interviewing all include strategies that go beyond simple patient education to produce behavior change. Although the goals of brief counseling may seem modest, these limited objectives are also more likely to be attainable. Two 15-minute interventions, with components similar to FRAMES, were associated with reduced drinking and reduced a number of hospital days among male patients [6]. As a respected authority for patients, the physician’s targeted counseling, although time-limited, may exert wide-ranging effects.

References [1] Wedding D, Mengel M. Models of integrated care in primary care settings. In: Haas LJ, editor. Handbook of primary care psychology. New York: Oxford; 2004. p. 47–60. [2] Miranda J, Hohmann AA, Attkisson CC. Epidemiology of mental disorders in primary care. In: Miranda J, Hohmann AA, Atkisson CC, Larson DP, editors. Mental disorders in primary care. San Francisco (CA): Jossey-Bass; 1994. p. 3–15. [3] Beardsley RS, Gardocki GJ, Larson DB, et al. Prescribing of psychotropic medications by primary care physicians and psychiatrists. Arch Gen Psychiatry 1988;45:1117–9. [4] Haas LJ, DeGruy FV. Primary care, psychology, and primary care psychology. In: Haas LJ, editor. Handbook of primary care psychology. New York: Oxford; 2004. p. 5–20. [5] National Institute on Alcohol Abuse and Alcoholism. Brief intervention for alcohol problems. Alcohol Alert 1999;43:1–4. [6] Fleming MF, Barry KL, Manwell LB, et al. Brief physician advice for problem alcohol drinkers: a randomized controlled trial in community-based primary care practices. JAMA 1997;277(13):1039–45. [7] Gatchel RJ, Oordt MS. Clinical health psychology and primary care: practical advice and clinical guidance for successful collaboration. Washington, DC: American Psychological Association; 2003.

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[8] Strosahl K. Integrating behavioral health and primary care services: the primary mental health care model. In: Blount A, editor. Integrated primary care: the future of medical and mental health collaboration. New York: Norton; 1998. p. 139–66. [9] Simon GE, VonKorff M, Barlow W. Health care costs of primary care patients with recognized depression. Arch Gen Psychiatry 1995;52:850–6. [10] Byrd MR, O’Donohue WT, Cummings NA. The case for integrated care: coordinating behavioral health care with primary care medicine. In: O’Donohue WT, Byrd MR, Cummings NA, et al, editors. Behavioral integrative care. New York: Brunner-Routledge; 2005. p. 1–14. [11] Cummings NA. Does managed mental health care offset costs related to medical treatment? In: Lazarus A, editor. Controversies in managed mental healthcare. Washington, DC: American Psychiatric Press; 1996. p. 213–27. [12] Strosahl KD, Sobel D. Behavioral health and medical cost offset effect: current status, key concepts, and future applications. HMO Pract 1996;10:156–62. [13] Kroenke K, Mangelsdorff AD. Common symptoms in ambulatory care: incidence, evaluation, therapy, and outcome. Am J Med 1989;86:262–6. [14] Creed F, Olden KW. Gastrointestinal disorders. In: Levenson JL, editor. Essentials of psychosomatic medicine. Washington, DC: American Psychiatric Press; 2007. p. 55–74. [15] Glanz K, Oldenburg B. Utilizing theories and constructs across models of behavior change. In: Patterson R, editor. Changing patient behavior: improving outcomes in health and disease management. San Francisco (CA): Jossey-Bass; 2001. p. 25–40. [16] Rollnick S, Butler C, Stott N. Helping smokers make decisions: the enhancement of brief intervention for medical practice. Patient Educ Couns 1997;31:191–203. [17] Fisher L, Ransom DC. Developing a strategy for managing behavioral health care within the context of primary care. Arch Fam Med 1997;6:324–33. [18] Balkrishnan R, Hall MA, Mehrabi D, et al. Capitation payment, length of visit, and preventive services: evidence from a national sample of outpatient physicians. Am J Manag Care 2002;8:332–40. [19] Stuart MR, Lieberman JA. The fifteen minute hour: applied psychotherapy for the primary care physician. Second edition. Westport (CT): Praeger; 1993. [20] Stuart MR, Lieberman JA. The fifteen minute hour: practical therapeutic interventions in primary care. Third edition. Philadelphia: Saunders; 2002. [21] Gifford EV, Ritsher JB, McKellar JD, et al. Acceptance and relationship context: a model of substance use disorder treatment outcome. Addiction 2006;101:1167–77. [22] Kadden RM, Cooney NL. Treating alcohol problems. In: Marlatt GA, Donovan DM, editors. Relapse prevention. Second edition. New York: Guilford; 2005. p. 65–91. [23] Foster GD, Wadden TA, Vogt RA, et al. What is a reasonable weight loss? Patients’ expectations and evaluations of obesity treatment outcomes. J Consult Clin Psychol 1997;65: 79–85. [24] Velcier WF, Prochaska JO, Fava JL, et al. Smoking cessation and stress management: applications of the transtheoretical model of behavior change. Homeostasis 1998;38: 216–33. [25] Zweben A, Zuckoff A. Motivational interviewing and treatment adherence. In: Miller WR, Rollnick SR, editors. Motivational interviewing: preparing people for change. 2nd edition. New York: Guilford; 2002. p. 299–319. [26] Dodgen CE. Nicotine dependence: understanding and applying the most effective treatment interventions. Washington, DC: American Psychological Association; 2005. [27] Whitehead D, Doherty JW. Systems dynamics in cigarette smoking: an exploratory study. Fam Syst Med 1989;7:264–73. [28] Mullen PD, Green LW, Persinger GS. Clinical trials of patient education for chronic conditions: a comparative analysis of intervention types. Prev Med 1985;14:753–81. [29] Maurer R. One small step can change your life: the Kaizen way. New York: Workman; 2004. [30] Searight HR. Behavioral medicine: a primary care approach. Philadelphia: Taylor & Francis; 1999.

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[31] DiClemente CC, Velasquez MM. Motivational interviewing and the stages of change. In: Miller WR, Rollnick S, editors. Motivational interviewing. 2nd edition. New York: Guilford Press; 2002. p. 201–16. [32] Fiore MC, Croyle RT. Progress, setbacks, and future needs. Preventing 3 million premature deaths and helping 5 million smokers quit: a national action plan for tobacco cessation. Am J Public Health 2004;94:205–10. [33] Miller WR, Rollnick S. What is motivational interviewing? In: Miller WR, Rollnick S, editors. Motivational interviewing: preparing people for change. 2nd edition. New York: Guilford; 2002. p. 33–42. [34] Emmons KM, Rollnick S. Motivational interviewing in health care settings: opportunities and limitations. Am J Prev Med 2001;20:68–74. [35] Senft RA, Freeborn DK, Polen MR, et al. Brief intervention in a primary care setting for hazardous drinkers. Am J Prev Med 1997;13:464–70. [36] Butler CC, Rollnick S, Cohen D, et al. Motivational consulting versus brief advice in general practice: a randomized trial. Br J Gen Pract 1999;49:611–6.

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Integrating Mental Health and Primary Care Stephen Thielke, MD, MA*, Steven Vannoy, PhD, Ju¨rgen Unu¨tzer, MD, MPH, MA Geriatric Mental Health Services, Department of Psychiatry and Behavioral Sciences, Box 356560, University of Washington, Seattle, WA 98195, USA

Mental health and primary care delivery systems have, by virtue of their histories and the patients they treat, evolved to operate quite differently. For example, attention to multiple medical issues, health maintenance, and structured diagnostic procedures are standard elements of primary care that are seldom incorporated into mental health care systems. A multidisciplinary approach to treatment, group care, and case management are common features of mental health treatment settings that are only rarely used in primary care practices. Advances in the treatments for mental health disorders and increased knowledge of the integral link between mental health and physical health encourage the treatment of mental health disorders in primary care settings, which reach the most patients. Effective integration of mental health care into primary care requires systematic and pragmatic change that builds on the strengths of both mental health and primary care. At first glance, the following conditions might seem to be necessary for better treatment of common mental disorders in primary care [1]:  Patients who have mental health disorders must be systematically identified.  Primary care providers must apply the right treatments for mental health disorders, which requires

Support for this article was provided by National Research Service Award T-32 Fellowship (Thielke, Vannoy); the John A Hartford Foundation (Unu¨tzer); the Paul Beeson Physician Faculty Scholars Award from the American Federation for Aging Research (Unu¨tzer); and the National Institute of Mental Health (Unu¨tzer). * Corresponding author. E-mail address: [email protected] (S. Thielke). 0095-4543/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pop.2007.05.007 primarycare.theclinics.com

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Sufficient education about mental health diagnosis and treatment Sufficient experience in dealing with patients who have mental health disorders Accessible, clear, evidence-based guidelines for treatment Availability of consultation with experts in mental health  There must be enough mental health specialists available to accept referrals for management of complicated cases. Despite the intuitive appeal of such requirements, this article concludes that none of the strategies to satisfy them has been found in research trials to be of significant benefit for improving patient-level mental health outcomes in primary care. Specifically, there is little evidence of positive patient level outcomes from efforts focused on screening, provider training, dissemination of guidelines, referral to mental health specialists, or colocating mental health practitioners in primary care settings. Instead, there is strong evidence that the best outcomes for treating common mental health disorders in primary care result from the application of ‘‘collaborative care,’’ an approach in which primary care and mental health providers collaborate in an organized way to manage common mental disorders. Such programs are pragmatic and apply principles of chronic disease management, such as establishing and sustaining effective communication and collaboration between primary care and mental health providers and care managers who can facilitate such collaboration, support systematic diagnosis and outcomes tracking, and facilitate adjustment of treatments based on clinical outcomes (stepped care). This article focuses on key research evidence from efforts to improve mental health provision through systemic changes to primary care, with less attention to the patient-level barriers for accessing mental health care, the efficacy of specific treatments for mental health disorders, or the logistical issues involved in implementing interventions in the real world. Because of the limited space available, this attention to process rather than content will omit much of the important research about how to improve mental health services to populations, but will deal specifically with how primary care settings can adapt to provide services that have been shown to improve outcomes. Primary care and mental health disorders Box 1 reviews some of the common barriers to effective treatment of common mental disorders in primary care. These elements, synthesized from work on improving mental health provision [2–17], are meant to illustrate the multiple factors that complicate attempts at identifying and treating mental health conditions in primary care settings. Disease process level Mental health disorders are a challenge to understand, identify, and treat. The term ‘‘mental health disorders’’ covers a broad range of disorders and

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Box 1. Barriers to treating mental disorders in primary care Disease process ‘‘Mental health disorders’’ include a broad range of conditions and symptoms Limited understanding of etiology and pathophysiology Nonspecific presentation, often overlapping with somatic symptoms Undifferentiated symptoms crossing multiple categories of illness Diagnosis based almost entirely on lengthy history and mental status examination Symptoms often chronic and complex at the time of presentation Treatment for complex disorders often unsuccessful, even in controlled settings Other disorders self-limited, requiring no formal treatment Patient Multiple comorbidities and priorities competing for attention Stigma associated with mental illness; negative beliefs about treatment Symptoms discourage care seeking and self-management (eg, depression) Provider Trained in medical model, not psychotherapy Competing demands and knowledge overload System Little monetary incentive for addressing and treating mental disorders in primary care Time constraints and limited follow-up available Little attention to systematically measuring mental health outcomes Limited access to mental health specialists Limited capacity to provide evidence-based psychosocial treatments in primary care

conditions, related to behavior, mood states, interpersonal relations, cognitive ability, attention, identity, and development. Unlike most medical conditions, providers often have little idea of what causes mental health conditions, or what pathophysiological changes occur during them. The most common disorders, related to mood, anxiety, and personality pathology, frequently manifest with somatic or nonspecific complaints [18]. In the setting of other medical comorbidities, it can take several visits before

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a mental health problem is even identified, often after other disease processes are excluded. Mental health symptoms may become chronic or entrenched before care is sought. Making an accurate diagnosis requires taking a detailed and complex history and understanding patient concerns [19], all within limited time [20]. Alternately, there are some common mental health disorders, such as mild depression, which may remit without formal treatment, and for which a ‘‘watchful waiting’’ approach may be appropriate, but it can be hard to differentiate these from those requiring acute attention [21]. Even when chronic or stable over time, psychiatric symptoms rarely fit a neat diagnostic category, and there is significant overlap of mood, anxiety, substance abuse, and personality disorders [22,23], which can complicate efforts to diagnose and treat with accepted treatment algorithms for a single disorder. There are multiple criteria and diagnostic tests for mental health conditions (as in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]), but most of them are quite detailed and lengthy to administer, and all require subjective interpretation by the practitioner. This is considerably different from conditions such as hypertension or diabetes, which can be ascertained through at most a few straightforward quantitative measurements and a focused clinical evaluation. Once identified, some mental health conditions are resistant to initial treatment, even under ideal circumstances, such as in clinical trials with ‘‘clean’’ populations that have no significant comorbidities, and many patients end up ‘‘better but not well.’’ Patient level Patients who have mental disorders have, on balance, more somatic complaints and more medical comorbidities than those without mental health problems [24]. They thus often have a full list of medical problems to address in primary care, and the mental health condition must compete for attention with other health problems that often seem more. During a time-limited primary care visit there is often very little time left for mental health issues [25]. Stigma about mental health problems persists in society, and can discourage patients from talking openly about their psychological problems, and discourage providers from asking patients about such problems. Because of such stigma, individuals are often unaware that the way they feel emotionally, mentally, and physically is because of a mental disorder for which treatment exists, or that their primary care provider can help them treat it. Patients often have negative views of treatments such as psychotropic medications [26,27], and they often do not take such medications as prescribed [28–30]. In addition to stigma, the very nature of some mental health disorders, such as depression, cognitive impairment, or personality disorders, may limit patients’ motivation or capacity to seek care or to be an active participant in their health care. Indeed, by definition, almost all mental disorders involve impairment in functioning or self-care. Patients who have severe depression or thoughts of suicide may have a sense of

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hopelessness and futility with regard to potential treatments. Patients who have substance abuse disorders often have ambiguous motivation for initiating or sustaining care. These factors require the practitioner to work harder (ie, apply more skill and time) to progress from initial presentation to diagnosis and successful treatment. Provider level Primary care providers have been trained in a medical model, and most of the treatments they apply involve medications, procedures, or advice. Medications are also a mainstay of treating mental health conditions in primary care, but there is strong evidence that an effective therapeutic alliance and formal psychotherapy are also important components of effective treatment for common conditions such as mood or anxiety disorders [31–33]. Evidencebased psychotherapies such as cognitive-behavioral therapy, interpersonal therapy, or problem-solving treatment require both trained providers and a substantial time commitment (eg, 30 minutes to an hour a week for 6–12 sessions), and are often provided by non-medically trained providers such as psychologists and social workers. Although primary care providers often become, through experience, experts in understanding and working with interpersonal dynamics in clinical settings, they are not able to offer time-intensive psychotherapy to their patients because of short appointments and limited reimbursement for longer visits. Primary care providers are expected to keep current on a broad range of medical topics, but current recommendations and guidelines about evidence-based care for mental disorders can be hard even for specialists to follow [34]. An ‘‘overload’’ of shifting information about evidence-based treatments can make it difficult to apply up-to-date specialty recommendations for mental health treatments in primary care. System level Primary care reimbursement systems generally apply few financial incentives for treating mental health problems with increased time or effort. For instance, a lengthy visit for a Medicare patient with a primary care diagnosis of depression may lead to a smaller reimbursement than several brief visits focused on somatic complaints. Primary care visits are almost always timelimited, and tight schedules make it difficult to increase visit length to address complex mental health issues [25]. For the same reason, regular follow-up can be hard to accommodate in busy schedules. Mental health outcomes are often difficult to track, and there are few procedures in place for systematically measuring and monitoring symptoms (unlike other medical outcomes such as weight or blood pressure, which are usually measured at each visit) [35]. Time constraints, lack of strong incentives, and absence of clear outcomes can make it difficult to address mental health issues in primary care, and attention may shift preferentially to those issues that can be more readily addressed.

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Approaches to integration Despite these barriers, most patients seek initial care for mental health complaints in primary care settings [36,37]. Box 2 outlines some of the major strategies attempted to improve mental health delivery in primary care [38–40]. Each of these is described, and the evidence base for its outcomes briefly reviewed. Systematized screening for mental health conditions As described above, many aspects of primary care make it difficult to identify mental health disorders, and multiple studies have demonstrated that mental health conditions are underdiagnosed in primary care [41–44]. Ideally, systematic screening could enable primary care physicians to discover mental health disorders sooner and treat them better. To this end, mandates have been developed for primary care to better ‘‘screen, detect, treat, and improve’’ common mental health conditions such as depression [45]. Controlled studies have shown that screening and systematic feedback to providers about mental health problems can increase diagnosis rates [46]; however, screening alone has been found to have limited effects on clinical outcomes in several large controlled trials, and for large populations, screening has not demonstrated clinical benefits [47] or cost-effectiveness [48,49]. For depression, the U.S. Preventive Services Task Force now recommends that adults be screened only if systems exist to ensure accurate diagnosis, effective treatment, and follow-up [50]. A recent review suggests that screening approaches do not perform as expected, because they involve considerable performance burden (using imperfect instruments to measure and communicate variables), interpretation burden (the need for further tests, given the low predictive value of screening instruments), and treatment burden (the need to initiate and sustain effective treatment) [51]. These findings reinforce that even though systematic screening for common mental disorders in primary care may improve recognition, screening alone may simply

Box 2. Interventions geared at improving mental health in primary care Systematic screening for mental health conditions Education and training of primary care practitioners Production and dissemination of treatment guidelines Referral to mental health specialists (on-site or off-site) Tracking mental health outcomes with ‘‘mental health laboratories’’ Collaborative care models, involving care managers and stepped care

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produce a presumptive diagnosis that can complicate care [52] without improving health outcomes, unless a practice has the capacity to effectively diagnose and manage these disorders. Education and training of primary care practitioners Intuitively, one would expect that primary care providers who had better training in the recognition and management of mental health disorders would produce better patient outcomes than those with less training. Most of the efforts at improving mental health treatment in primary care are thus directed at educating providers about diagnostic criteria, treatment algorithms, and prescription of psychiatric medications. Programs of this type account for a majority of the effort and money spent on improving mental health delivery in primary care [53]. For example, there exist an abundance of training programs on mental health topics for primary care resident physicians, continuing medical education courses for established primary care providers, pharmaceutical company-supported educational programs about psychotropics, and continuous quality improvement (CQI) initiatives for entire health care systems. One highly targeted approach, academic detailing, seems to have particular promise because it involves face-to-face contact between a primary care provider and an expert to discuss evidence-based guidelines, usually focused on realistic cases [54]. Under scrutiny, these education and training approaches have not been shown to have consistent beneficial effects on either provider behaviors or patient-level outcomes, especially long-term. A comprehensive review of attempts to improve the psychiatric knowledge, skills, and attitudes of primary care physicians found a dearth of quality evidence for provider-level change or improved patient-level outcomes [55]. The evidence for specific effects is mixed, depending on the type of intervention and the outcomes measured. A short educational program was shown to improve primary care physician knowledge and adherence to guidelines, but the effects did not seem to improve diagnosis, and there were no patient-level outcomes measures assessed [56]. A program to improve management of depression involving 20 hours of physician training improved adherence to recommendations and had modest effects in patient outcomes at 3 months, but there were no benefits observed at 1 year [57]. Similar negative findings with regard to outcomes have been reported from brief training followed by case consultation [58], and didactic training followed by videotapes and follow-up sessions [59]. Academic detailing and CQI for depression care have been assessed through two randomized trials that showed moderate changes in prescribing behavior, but no difference in patient outcomes [60,61]. Such programs are quite costly to administer, at roughly $15,000 per patient-level quality-adjusted life year (QALY) [62]. This research suggests that physician knowledge is either not the primary barrier to improving mental health outcomes for primary patients, or that it is not readily

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amenable to change through educational interventions. Using the most conservative interpretation of the available evidence on provider training, it seems reasonable to conclude that skills and knowledge related to mental health may be necessary but not sufficient factors to improve outcomes of patients who have common mental disorders. Production and dissemination of treatment guidelines Instead of increasing primary care providers’ understanding of and experience with mental health conditions, an alternative approach codifies treatments into specific guidelines for ‘‘what to do’’ with mental health diagnoses. These guidelines are often developed by specialist experts, and generally are grounded in research evidence. As such, they work to encourage treatments that have been shown to work in controlled clinical trials, and would be expected, if followed, to improve outcomes. Guidelines of this type have been developed for most of the common mental health conditions seen in primary care [63–66], and considerable effort has been applied to making them as useful as possibledfor instance in the maxim recommending that, ‘‘Good guidelines are simple, specific, and user friendly, focus on key clinical decisions, are based on research evidence, and present evidence and recommendations in a concise and accessible format’’ [67]. Within psychiatry, there is some evidence that adherence to algorithms can improve outcomes compared with usual care, at least within controlled settings [68]. In examining how guidelines change provision of care, there is little evidence of significant change in practice behaviors or patient outcomes. Few studies have looked carefully at the effect of treatment guidelines in primary care, and those that have done so failed to show substantial improvements in patient outcomes that can be related to the application of such guidelines. For instance, a controlled study of patients who had anxiety disorder in primary care, comparing referral to a psychiatrist, guided self-help recommended by the primary care provider, and a highly-structured Anxiety Disorder Guideline, found similar moderate improvement from all approaches, with the guidelines more difficult to carry out [69]. An investigation of pediatric attention deficit hyperactivity disorder (ADHD) guidelines found that the complexity of the clinical presentations and the lack of systems for providing additional support and follow-up often rendered the guidelines inapplicable or unproductive [70]. For depression, there is some evidence that ‘‘nonalgorithmic’’ factors such as greater patient involvement in decisions are associated with better outcomes [71,72]. There are some large-scale studies ongoing to assess the utility of treatment recommendations for treating depression in primary care [73] that may ultimately bolster specific guideline approaches. At present, however, there is little evidence that more or different types of guidelines for primary care providers are sufficient to improve mental health outcomes.

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Increased referral to mental health specialists Given the barriers to providing mental health care within primary care, there has been interest in interventions that increase the role of mental health specialists in managing mental health disorders. This can be effected either by increasing the availability of external mental health specialists who can evaluate patients and either assume treatment or make recommendations for care (‘‘enhanced specialty care’’), or by having mental health specialists located within primary care clinic settings (‘‘colocated care,’’ not to be confused with ‘‘collaborative care,’’ with which it has been used synonymously at times). Such approaches reduce the role of the primary care provider to identifying possible mental health conditions, and then either referring the patient to a mental health specialist or consulting with that specialist about the best course of action, especially for complicated or nonresponsive cases. These strategies seem to capitalize on the strengths of both systems: the primary care provider’s connection with, history with, and comprehensive knowledge of the patient, combined with the mental health expert’s skill at diagnosis and treatment and capacity for longer or more frequent visits. The more complex the patients are, or the less responsive to treatment, the more the specialist would take responsibility for their care. Such colocation strategies were adopted in the mid-1990s in several large health care systems in the United States (Kaiser Permanente Northern California and the Veteran’s Administration Healthcare System), and continue to be used to varying degrees, but there are no published outcomes from these real-world experiments, and there is little evidence from controlled trials about the effectiveness of such colocated services. Some research has suggested that integrated care is better accepted by patients than traditional care [74], but the samples in such studies have been quite restricted, and no changes in outcome were documented. The PRISM-E (Primary Care Research in Substance Abuse and Mental Health for Elderly) study compared integrated care with enhanced specialty referral for depression outcomes, and found better patient engagement in integrated care, but no significant differences in patient outcomes between these two strategies at 6 months [75,76]. Treatment response rates were close to those found in usual care in other studies, suggesting that neither approach may be substantially more effective than care as usual. Similarly, a study of enhanced specialty care involving three visits with a specialist around patient-specific treatment recommendations did not show any substantial difference from standard primary care in the treatment of depression [77]. Increasing specialty mental health referrals also has significant operational problems. Rates of engagement with specialty mental health care providers are low overall, and especially so for ethnic minorities [78] or older patients [77]. Thus many patients referred for specialty care never receive such care, or have only few visits in the specialty mental health care sector before finding their way back to primary care. Moreover, most specialty providers are already busy with caseloads of patients who have severe and

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often chronic mental illnesses, and it is unrealistic to expect that they would be able to take on a large number of new patients from primary care, particularly in rural and underserved areas where specialty mental health resources are extremely limited. There are some novel approaches for increasing the connections of primary care patients and providers with specialty providers, such as telepsychiatry [79–81], but these have not been tested in large trials. In general, attempts to improve referral access to mental health specialists have had disappointing results with regards to improving outcomes of primary care patients who have common mental disorders. Tracking mental health outcomes with ‘‘mental health laboratories’’ Many of the key barriers to managing mental health disorders in primary care relate to the mismatch between primary care delivery systems and those of mental health. For instance, primary care relies on diagnostic procedures such as laboratory tests for health maintenance, work-up of diseases, and tracking of treatment effectiveness. These objective findings can direct straightforward treatment protocols managed by the provider. This is in contrast to mental health systems, which assess patients primarily through subjective interactions, and use diagnostic laboratory procedures only in special circumstances, such as to check serum levels of medications or to assess general health before starting a treatment. One innovative approach to improving mental health treatments in primary care settings is to treat and monitor psychiatric symptoms in the same way that other ‘‘lab values’’ are used to manage patients who have chronic medical disorders such as diabetes or hyperlipidemia. An innovative program called the ‘‘Behavioral Health Laboratory’’ involves a telephone call from a health technician, asking questions from established psychiatric rating scales such as the Patient Health Questionnaire-9 (PHQ-9) for depression. The results are scored by a computer algorithm, and are conveyed to the primary care physician, who can treat or refer to on-site mental health services available in most Veterans Administration (VA) medical centers. This intervention has been tested in a large VA primary care clinic population, with increased identification of patients who have elevated psychiatric symptoms and comorbidities [82]. In this setting, such a ‘‘laboratory’’ was relatively low-cost and easily implemented, a major advantage with regards to the ability to disseminate and sustain an innovation. Improved patient-level outcomes have yet to be demonstrated in a randomized trial, and further research will show if this is a feasible and effective means of being able to manage mental health conditions in other primary care systems. Theoretically and operationally, this approach has many similarities to evidence-based collaborative care programs discussed below. Collaborative care models, involving care managers and stepped care Collaborative care as defined in this article refers to a treatment model quite different from that of either primary care or specialty mental health

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care. The emphasis is on managing mental disorders as chronic disease rather than treating acute symptoms or complaints. The Chronic Care Model as outlined by Wagner and colleagues [83] provides the underpinnings for such interventions, and involves improvements in six areas: (1) self-management support, (2) clinical information systems, (3) delivery system redesign, (4) decision support, (5) health care organization, and (6) community resources [84,85]. Interventions directed by these principles have focused on involving the patient in care decisions (eg, offering a choice between antidepressant medications and psychotherapy in the treatment of depression), developing collaborative approaches to optimize complementary roles of different providers (eg, primary care providers and consulting mental health specialists), and organizing care around commonly defined and recorded treatment goals and systematic measurement of relevant health outcomes to determine if such goals are being met or if changes in treatment are needed [86]. Effective collaboration of primary care providers and consulting mental health specialists is often facilitated by a new type of professional, the care manager. This approach is similar to evidence-based care management programs for chronic medical disorders such as diabetes or congestive heart failure (CFH), in which diabetes nurse educators or CHF care managers function in this role [87]. In the area of mental health, the chief roles of care managers include [88,89] (1) educating patients about their illness; (2) involving and supporting patients in making treatment decisions; (3) monitoring treatment outcomes using structured rating scales; (4) ensuring adequate follow-up; (5) discussing and encouraging medication treatment as initiated by the primary care provider; (6) providing brief counseling using evidence-based structured techniques such as behavioral activation, motivational interviewing, or problem solving treatment in primary care; (7) facilitating consultation from mental health specialists; and (8) facilitating referral to appropriate mental health specialty care or other community resources for patients who are not improving in primary care. Similar to other successful chronic disease management programs, the care manager’s job is devoted to managing patients’ chronic conditions, in this case a mental disorder such as depression or an anxiety disorder. Most treatment occurs in primary care, and much of the patient contact is with the care manager, often over the telephone. Treatment goals emphasize measurable reductions in the symptoms that are captured by structured mental health rating scales; scheduled measurements and feedback about these are an essential element of collaborative care. Such systematic outcomes tracking is similar to the ‘‘mental health laboratory’’ described above, but is scheduled rather than prescribed as indicated. Stepped-care algorithms are often applied to guide the initiation and modification of treatment based on systematic clinical outcomes, with changes in treatment such as augmentation of medications or a combination of medications and psychotherapy if patients are not improving with initial treatment in primary care.

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Care managers are responsible for tracking a caseload of patients who have common mental disorders such as depression in a primary care practice. They also increase patient contact and may enhance the therapeutic alliance, which works both toward improved outcomes and decreased dropout from treatment [88], and which reduces the risk of patients staying on ineffective treatments for too long. A designated mental health expert, usually a psychiatrist, provides regular systematic caseload supervision for care managers, as well as consultation and backup to care managers and primary care providers, focusing on patients who are not improving as expected. Table 1 describes the core processes and provider roles that define such evidence-based collaborative care [38,90,91]. Collaborative care thus differs from traditional primary care in two essential ways. First, a care manager whose job focuses on managing one or more common mental disorders supports treatment that is initiated by the primary care provider and supervised indirectly by a mental health specialist. Second, proactive follow-up and systematic tracking of outcomes is essential, and outcomes are the subject of communication between the different providers and between the providers and the patient, and also are the main information with which treatment decisions are made (ie, whether to continue the same treatment or to make a change). Within this framework, care managers support effective collaboration between patients, primary care providers, and consulting mental health specialists, facilitating treatment changes indicated by systematic tracking of clinical outcomes according to evidence-based treatment guidelines. Over 35 randomized clinical trials of such collaborative care models for depression in the United States and Europe have demonstrated their superiority over usual care, with advantages in retention in treatment, clinical outcomes, employment rates, functioning, and quality of life (see Bower and colleagues [92], Gilbody and colleagues [93], and Williams and colleagues [94] for recent meta-analyses of these multifaceted interventions). For instance, in the IMPACT (Improving Mood and Promoting Access to Collaborative Treatment) trial, the largest trial of collaborative care for depression to date, 45% of the depressed older adults in the collaborative care arm had a substantial treatment response (50% or greater reduction in depression symptoms from baseline), compared with only 19% in usual care [88]. Similar positive results have been obtained in randomized trials of collaborative care for depression in nongeriatric adults [93], as well as for panic and generalized anxiety disorder [95], bipolar disorder [96–99], and Alzheimer’s disease [100]. Collaborative care seems to benefit ethnic minority groups, who otherwise have low rates of care and poor outcomes [101–103], as well as adolescents and older adults who have comorbid medical illness [104,105]. These programs are not only more effective, but also more cost-effective than usual care [106–108], and they have been successfully implemented in a variety of diverse health care settings [109–114].

Table 1 Core processes and provider roles in collaborative care Providers Care manager

Mental health expert

Primary care provider

Systematic diagnosis and tracking of outcomes

Measure, document, and track mental health outcomes.

Supervise caseloads with care managers, based on measured outcomes. Consult on diagnosis for difficult cases.

Receive feedback from care managers about outcomes.

Database of symptom severity over time for all patients

Educate about medications and their use; encourage adherence. Counsel patients. Facilitate treatment change or referral to mental health as clinically indicated.

Consult on patients who are not improving as expected. Recommend additional treatments or referral to specialty mental health care according to evidence-based guidelines. No formal role during maintenance phase

Prescribe medications. Reinforce and support treatment plan. Collaborate with mental health expert and care manager to make necessary treatment changes. Reinforce relapse prevention plan.

Treatments received Changes to treatment

Stepped care: a) Changes to treatment using evidence-based algorithm if patient is not improving

b) Relapse prevention once patient is improved

Track symptoms after initial improvement; follow algorithms.

Reminders to ensure ongoing contact and symptom monitoring

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Process

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Why do some approaches work whereas others do not? Taken as an aggregate, the available evidence indicates that many of the strategies that have been attempted to improve mental health treatment in primary care have not been successful. Multifaceted approaches used in trials of collaborative care are currently the most promising efforts, although even such multifaceted programs are not successful for all patients. The evidence for the effectiveness of collaborative care comes not only from controlled clinical trials, but also from the implementation of such evidencebased models in ‘‘real world’’ health care settings [109]. In the light of the barriers to integration discussed earlier, the differences between collaborative care and the other approaches merit attention: why should collaborative care succeed where other approaches have failed? Efforts to enhance mental health in primary care, through a variety of means such as additional screening, more education of providers, or more specific treatment guidelines, have been found not to make much consistent measurable difference in patient outcomes. One of the main reasons for this lack of effect is probably because primary care systems are, in essence, not organized to treat mental health disorders. Instead, they are organized to manage acute diseases and the health maintenance of broad populations who have various medical conditions, but not to detect, diagnose, retain, and treat individuals who have mental health disorders, which are often qualitatively different. This key systematic barrier would be expected to persist no matter how many new cases are identified by systematic screening, no matter how expert primary care providers are about psychiatric disorders and their treatment, no matter how specific the guidelines and algorithms for treatment are, and no matter how many specialists are available for consultation and referral. Evidence-based collaborative care programs do not require primary care providers to take on all of the responsibility for identifying and treating what can be complex and often nebulous conditions, or to undergo major changes in the way they practice medicine. These programs also do not simply colocate primary care providers and mental health specialists to practice in parallel under the same roof. Instead, these approaches build on and integrate strengths and approaches from both primary care (eg, the systematic measurement of key health outcomes such as a PHQ-9 used in the ‘‘behavioral health laboratory,’’ or stepped care approaches used to treat other chronic medical disorders such as hypertension or diabetes), mental health specialty care (eg, a multidisciplinary approach to treatment with caseload supervision by psychiatrists or other experienced mental health professionals, and the use of evidence-based psychosocial treatments in addition to medication treatment), and evidence-based approaches to the management of chronic medical illnesses (such as the use of care managers to facilitate patient education, proactive follow-up, systematic tracking of outcomes, and adjustment of treatments based on clinical outcomes). These

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elements of care are provided in primary care, a setting that is easily accessible and familiar to the patient, carries less stigma than specialty mental health settings, and allows for closer coordination of treatment for the patient’s medical and mental disorders. The main change that is expected of primary care providers and specialty mental health care providers in collaborative care is that they will pay attention to the symptom-related outcomes that are systematically documented for each patient, and will collaborate to initiate changes in the treatment plan for patients who are not improving, with support from a care manager who can help facilitate these changes and who is supervised by a consulting mental health specialist. In collaborative care, primary care providers recognize a new agent in the treatment team (the care manager), and respond to a new type of information (regular, quantitative mental health status and focused recommendations for treatment change by a consulting mental health expert). The mental health provider offers oversight and supervision for a caseload of patients managed in a primary care setting, following systematic measures of relevant patient outcomes and focusing on treatment recommendations for patients who are not improving as expected, or who represent particular diagnostic or therapeutic challenges. A recent metaanalysis of collaborative care interventions for depression in primary care concludes that the three ‘‘essential elements’’ of effective collaborative care interventions are (1) support of medication management by primary care providers, (2) care management, and (3) supervision of care managers by consulting psychiatrists [94]. Another potentially important element in collaborative care that has only started to receive attention is patient self-management, which is one of the tenets of the Chronic Care Model, and which is accomplished by educating patients about their conditions and encouraging them to be responsible for managing them. Many collaborative care interventions actively involve patients in deciding treatment goals and treatments. For instance, in the IMPACT trial, patients worked with the care manager to decide whether to use antidepressant medications, problem solving treatment, or both [88]. There is some preliminary evidence from collaborative care treatment trials that patient self-management is associated with positive outcomes [97,115], and patient education and self-management have been parts of almost all successful collaborative care interventions [94]. This differs from approaches directed solely by the provider or by treatment algorithms, in which the patient is passive and has a very small role. Structured and well-organized information tracking systems have been another central element in effective collaborative care interventions [116]. Electronic health records (EHRs) have been used to manage the volumes of information that support screening, follow-up, patient contact, and treatments for large caseloads [117], and may allow successful accomplishment of the complex information-based tasks in chronic disease management [118]. Such information systems can prevent patients from ‘‘falling through the

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cracks,’’ and they can enhance transparency, because the occurrence of patient contacts, the treatments applied, and the outcomes are visible to all those involved in the care of the patient, including care managers, primary care providers, mental health providers and consultants, supervisors and administrators (as appropriate), and often other care managers within a care network. Effective caseload supervision by a consulting mental health specialist involves a systematic review of the outcomes of all of a care manager’s patients in a practice, using the information summarized in such an information system. As a result of such transparency, providers in a collaborative care program agree to ‘‘have their feet to the fire,’’ committing to an agreed common proximal goal in treating patients, the achievement of which will be known to the patient, the primary care provider, the care manager, the consulting mental health specialist, and (at an aggregate level) the administrators who have responsibility for quality of care at a clinic level. From a social psychology perspective, such a process that has identified, measured, and published treatment targets may have more effect than one where the goal is simply to ‘‘do a better job,’’ with no one paying careful attention to how well this is accomplished. Providers in such a collaborative care program would all share responsibility for patient outcomes, and would have incentive to collaborate effectively to achieve such outcomes. At a deeper level, there are key theoretical and operational differences between collaborative care and the other more traditional approaches to improving care. The traditional interventions are mainly ‘‘intention-driven,’’ seeking to improve care and improve outcomes through increased attention to elements assumed to be ‘‘essentials’’ for quality care: ready identification of cases through screening, improved provider knowledge and experience, evidence-based treatment algorithms, efficacious treatments, and readily available specialty referrals. The tacit premise of such approaches is that better components of care produce better care, which in turn produces better outcomes. Much of the energy is spent on action, and not on measurement. Collaborative care as defined in this article, on the other hand, is fundamentally pragmatic, concentrating on enacting specific procedures that have been found to improve outcomes in a measurable way. It does not ask that providers ‘‘know more’’ or ‘‘act differently,’’ but that they perform specific tasks: talking with patients and other providers in a structured manner, receiving feedback on outcomes, and following through with treatment changes when patients do not improve. The ends of collaborative care are also ultimately pragmaticddemonstrated improvement in measured patient outcomesdand the information tracking and exchange systems are designed to keep these ends paramount. Despite the substantial evidence for the effectiveness of collaborative care programs for common mental disorders such as depression, it is still unclear what the exact ‘‘magic’’ is in collaborative care, or which elements of such programs can be modified or adapted without changing outcomes. Further research aimed at identifying key components of such multifaceted

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programs and the most effective methods for adapting and implementing such programs in diverse health care settings is needed. Even well-implemented collaborative care programs leave substantial numbers of patients without a complete remission of their symptoms, and future work should identify evidence-based means of improving outcomes for all patients.

References [1] Kroenke K, Taylor-Vaisey A, Dietrich AJ, et al. Interventions to improve provider diagnosis and treatment of mental disorders in primary care. A critical review of the literature. Psychosomatics 2000;41(1):39–52. [2] Fickel JJ, Parker LE, Yano EM, et al. Primary caredmental health collaboration: an example of assessing usual practice and potential barriers. J Interprof Care 2007;21(2): 207–16. [3] Richards JC, Ryan P, McCabe MP, et al. Barriers to the effective management of depression in general practice. Aust N Z J Psychiatry 2004;38(10):795–803. [4] Simon GE, Fleck M, Lucas R, et al. LIDO group. Prevalence and predictors of depression treatment in an international primary care study. Am J Psychiatry 2004;161(9):1626–34. [5] Herrman H, Patrick DL, Diehr P, et al. Longitudinal investigation of depression outcomes in primary care in six countries: the LIDO study. Functional status, health service use and treatment of people with depressive symptoms. Psychol Med 2002;32(5):889–902. [6] Von Korff M, Katon W, Unu¨tzer J, et al. Improving depression care: barriers, solutions, and research needs. J Fam Pract 2001;50(6):E1. [7] Unu¨tzer J, Katon W, Sullivan M, et al. Treating depressed older adults in primary care: narrowing the gap between efficacy and effectiveness. Milbank Q 1999;77(2):225–56, 174. [8] Mechanic D. Barriers to help-seeking, detection, and adequate treatment for anxiety and mood disorders: implications for health care policy. J Clin Psychiatry 2007;68(Suppl 2): 20–6. [9] Horwitz SM, Kelleher KJ, Stein RE, et al. Barriers to the identification and management of psychosocial issues in children and maternal depression. Pediatrics 2007;119(1): e208–18. [10] Felker BL, Chaney E, Rubenstein LV, et al. Developing effective collaboration between primary care and mental health providers. Prim Care Companion J Clin Psychiatry 2006;8(1): 12–6. [11] Andersen SM, Harthorn BH. The recognition, diagnosis, and treatment of mental disorders by primary care physicians. Med Care 1989;27(9):869–86. [12] Williams JW. Competing demands: does care for depression fit in primary care? J Gen Intern Med 1998;13:137–9. [13] Klinkman MS. Competing demands in psychosocial care: a model for the identification and treatment of depressive disorders in primary care. Gen Hosp Psychiatry 1997;19:98–111. [14] Anfinson TJ, Bona JR. A health services perspective on delivery of psychiatric services in primary care including internal medicine. Med Clin North Am 2001;85(3):597–616. [15] Falloon IR, Ng B, Bensemann C, et al. The role of general practitioners in mental health care: a survey of needs and problems. N Z Med J 1996;109(1015):34–6. [16] Unu¨tzer J, Schoenbaum M, Druss BG, et al. Transforming mental health care at the interface with general medicine: report for the President’s commission. Psychiatr Serv 2006; 57(1):37–47. [17] Nutting PA, Rose K, Dickinson M, et al. Barriers to initiating depression treatment in primary care practice. J Gen Intern Med 2002;17(2):103–11. [18] Smith RC, Gardiner JC, Lyles JS, et al. Exploration of DSM-IV criteria in primary care patients with medically unexplained symptoms. Psychosom Med 2005;67(1):123–9.

588

THIELKE

et al

[19] Epstein RM, Shields CG, Franks P, et al. Exploring and validating patient concerns: relation to prescribing for depression. Ann Fam Med 2007;5(1):21–8. [20] Hyde J, Evans J, Sharp D, et al. Deciding who gets treatment for depression and anxiety: a study of consecutive GP attenders. Br J Gen Pract 2005;55(520):846–53. [21] Klinkman MS, Coyne JC, Gallo S, et al. False positives, false negatives, and the validity of the diagnosis of major depression in primary care. Arch Fam Med 1998;7(5):451–61. [22] McLaughlin TP, Khandker RK, Kruzikas DT, et al. Overlap of anxiety and depression in a managed care population: prevalence and association with resource utilization. J Clin Psychiatry 2006;67(8):1187–93. [23] Grant BF, Stinson FS, Dawson DA, et al. Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry 2004;61(8):807–16. [24] Katon W, Lin EH, Kroenke K. The association of depression and anxiety with medical symptom burden in patients with chronic medical illness. Gen Hosp Psychiatry 2007; 29(2):147–55. [25] Tai-Seale M, Bramson R, Drukker D, et al. Understanding primary care physicians’ propensity to assess elderly patients for depression using interaction and survey data. Med Care 2005;43(12):1217–24. [26] Givens JL, Datto CJ, Ruckdeschel K, et al. Older patients’ aversion to antidepressants. A qualitative study. J Gen Intern Med 2006;21(2):146–51. [27] Brown C, Battista DR, Bruehlman R, et al. Beliefs about antidepressant medications in primary care patients: relationship to self-reported adherence. Med Care 2005;43(12):1203–7. [28] Pampallona S, Bollini P, Tibaldi G, et al. Patient adherence in the treatment of depression. Br J Psychiatry 2002;180:104–9. [29] Sajatovic M, Blow FC, Kales HC, et al. Age comparison of treatment adherence with antipsychotic medications among individuals with bipolar disorder. Int J Geriatr Psychiatry 2007; [Epub ahead of print]. [30] Mukherjee S, Sullivan G, Perry D, et al. Adherence to treatment among economically disadvantaged patients with panic disorder. Psychiatr Serv 2006;57(12):1745–50. [31] Abbass AA, Hancock JT, Henderson J, et al. Short-term psychodynamic psychotherapies for common mental disorders. Cochrane Database Syst Rev 2006;(4):CD004687. [32] O’Kearney RT, Anstey KJ, von Sanden C. Behavioural and cognitive behavioural therapy for obsessive compulsive disorder in children and adolescents. Cochrane Database Syst Rev 2006;(4):CD004856. [33] Fava GA, Park SK, Sonino N. Treatment of recurrent depression. Expert Rev Neurother 2006;6(11):1735–40. [34] DeGruy FV 3rd. A note on the partnership between psychiatry and primary care. Am J Psychiatry 2006;163(9):1487–9. [35] Schoen C, Osborn R, Huynh PT, et al. On the front lines of care: primary care doctors’ office systems, experiences, and views in seven countries. Health Aff (Millwood) 2006;25(6):555–71. [36] Kroenke K, Spitzer RL, Williams JB, et al. Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Ann Intern Med 2007;146(5):317–25. [37] Wang PS, Berglund P, Kessler RC. Recent care of common mental disorders in the United States: prevalence and conformance with evidence-based recommendations. J Gen Intern Med 2000;15(5):284–92. [38] Vannoy SD, Powers D, Unu¨tzer J, et al. Models of care for treating late-life depression in primary care. Aging Health 2007;3(1):67–75. [39] Oxman TE, Dietrich AJ, Schulberg HC. Evidence-based models of integrated management of depression in primary care. Psychiatr Clin North Am 2005;28(4):1061–77. [40] Oxman TE, Dietrich AJ, Williams JW Jr, et al. A three-component model for reengineering systems for the treatment of depression in primary care. Psychosomatics 2002;43(6):441–50. [41] Katon W, Schulberg H. Epidemiology of depression in primary care. Gen Hosp Psychiatry 1992;14(4):237–47.

INTEGRATING MENTAL HEALTH AND PRIMARY CARE

589

[42] Higgins ES. A review of unrecognized mental illness in primary care. Prevalence, natural history, and efforts to change the course. Arch Fam Med 1994;3(10):908–17. [43] Brown C, Schulberg HC. Diagnosis and treatment of depression in primary medical care practice: the application of research findings to clinical practice. J Clin Psychol 1998; 54(3):303–14. [44] Tylee A, Walters P. Underrecognition of anxiety and mood disorders in primary care: why does the problem exist and what can be done? J Clin Psychiatry 2007;68(Suppl 2): 27–30. [45] Depression Guideline Panel, Agency for Health Care Policy and Research. Depression in primary care. Rockville, MD: U.S. Dept. of Health and Human Services, Agency for Health Care Policy and Research; 1993. [46] Gilbody S, Sheldon T, Wessely S. Should we screen for depression? BMJ 2006;332(7548): 1027–30. [47] Whooley MA, Stone B, Soghikian K. Randomized trial of case-finding for depression in elderly primary care patients. J Gen Intern Med 2000;15(5):293–300. [48] Valenstein M, Vijan S, Zeber JE, et al. The cost-utility of screening for depression in primary care. Ann Intern Med 2001;134(5):345–60. [49] Desai MM, Rosenheck RA, Craig TJ. Case-finding for depression among medical outpatients in the Veterans Health Administration. Med Care 2006;44(2):175–81. [50] Pignone MP, Gaynes BN, Rushton JL, et al. Screening for depression in adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;136(10): 765–76. [51] Nease DE Jr, Klinkman MS, Aikens JE. Depression case finding in primary care: a method for the mandates. Int J Psychiatry Med 2006;36(2):141–51. [52] Klinkman MS. The role of algorithms in the detection and treatment of depression in primary care. J Clin Psychiatry 2003;64(Suppl 2):19–23. [53] Thomson O’Brien MA, Freemantle N, Oxman AD, et al. Continuing education meetings and workshops: effects on professional practice and health care outcomes. Cochrane Database Syst Rev 2001;(2):CD003030. [54] Thomson O’Brien MA, Oxman AD, Davis DA, et al. Educational outreach visits: effects on professional practice and health care outcomes. Cochrane Database Syst Rev 2000; (2):CD000409. [55] Hodges B, Inch C, Silver I. Improving the psychiatric knowledge, skills, and attitudes of primary care physicians, 1950–2000: a review. Am J Psychiatry 2001;158(10):1579–86. [56] van Os TW, Ormel J, van den Brink RH, et al. Training primary care physicians improves the management of depression. Gen Hosp Psychiatry 1999;21(3):168–76. [57] Tiemens BG, Ormel J, Jenner JA, et al. Training primary-care physicians to recognize, diagnose and manage depression: does it improve patient outcomes? Psychol Med 1999;29(4): 833–45. [58] Lin EH, Simon GE, Katzelnick DJ, et al. Does physician education on depression management improve treatment in primary care? J Gen Intern Med 2001;16(9):614–9. [59] Thompson C, Kinmonth AL, Stevens L, et al. Effects of a clinical-practice guideline and practice-based education on detection and outcome of depression in primary care: Hampshire depression project randomised controlled trial. Lancet 2000;355(9199): 185–91. [60] Brown JB, Shye D, McFarland BH, et al. Controlled trials of CQI and academic detailing to implement a clinical practice guideline for depression. Jt Comm J Qual Improv 2000;26(1): 39–54. [61] Goldberg HI, Wagner EH, Fihn SD, et al. A randomized controlled trial of CQI teams and academic detailing: can they alter compliance with guidelines? Jt Comm J Qual Improv 1998;24(3):130–42. [62] Pyne JM, Rost KM, Zhang M, et al. Cost-effectiveness of a primary care depression intervention. J Gen Intern Med 2003;18(6):432–41.

590

THIELKE

et al

[63] Schulberg HC, Katon W, Simon GE, et al. Treating major depression in primary care practice: an update of the agency for health care policy and research practice guidelines. Arch Gen Psychiatry 1998;55(12):1121–7. [64] Nutt DJ, Fone K, Asherson P, et al. Evidence-based guidelines for management of attention-deficit/hyperactivity disorder in adolescents in transition to adult services and in adults: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2007;21(1):10–41. [65] Pilling S, Price K. Developing and implementing clinical guidelines: lessons from the NICE schizophrenia guideline. Epidemiol Psichiatr Soc 2006;15(2):109–16. [66] Peindl KS, Wisner KL, Hanusa BH. Identifying depression in the first postpartum year: guidelines for office-based screening and referral. J Affect Disord 2004;80(1):37–44. [67] Baldwin DS. Evidence-based guidelines for anxiety disorders: can they improve clinical outcomes? CNS Spectr 2006;11(10 Suppl. 12):34–9. [68] Dennehy EB, Suppes T, Rush AJ, et al. Does provider adherence to a treatment guideline change clinical outcomes for patients with bipolar disorder? Results from the Texas Medication Algorithm Project. Psychol Med 2005;35(12):1695–706. [69] van Boeijen CA, van Oppen P, van Balkom AJ, et al. Treatment of anxiety disorders in primary care practice: a randomised controlled trial. Br J Gen Pract 2005;55(519):763–9. [70] Leslie LK, Weckerly J, Plemmons D, et al. Implementing the American academy of pediatrics attention-deficit/hyperactivity disorder diagnostic guidelines in primary care settings. Pediatrics 2004;114(1):129–40. [71] Clever SL, Ford DE, Rubenstein LV, et al. Primary care patients’ involvement in decisionmaking is associated with improvement in depression. Med Care 2006;44(5):398–405. [72] Bergeson SC, Dean JD. A systems approach to patient-centered care. JAMA 2006;296(23): 2848–51. [73] Chatwin J, Kendrick T. THREAD study group. Protocol for the THREAD (THREshold for AntiDepressants) study: a randomised controlled trial to determine the clinical and costeffectiveness of antidepressants plus supportive care, versus supportive care alone, for mild to moderate depression in UK general practice. BMC Fam Pract 2007;8:2. [74] Yeung A, Kung WW, Chung H, et al. Integrating psychiatry and primary care improves acceptability to mental health services among Chinese Americans. Gen Hosp Psychiatry 2004;26(4):256–60. [75] Krahn DD, Bartels SJ, Coakley E, et al. PRISM-E: comparison of integrated care and enhanced specialty referral models in depression outcomes. Psychiatr Serv 2006;57(7):946–53. [76] Bartels SJ, Coakley EH, Zubritsky C, et al. Improving access to geriatric mental health services: a randomized trial comparing treatment engagement with integrated versus enhanced referral care for depression, anxiety, and at-risk alcohol use. Am J Psychiatry 2004;161(8): 1455–62. [77] Callahan CM, Hendrie HC, Dittus RS, et al. Improving treatment of late life depression in primary care: a randomized clinical trial. J Am Geriatr Soc 1994;42(8):839–46. [78] Takeuchi DT, Cheung MK. Coercive and voluntary referrals: how ethnic minority adults get into mental health treatment. Ethn Health 1998;3(3):149–58. [79] Baer L, Elford DR, Cukor P. Telepsychiatry at forty: what have we learned? Harv Rev Psychiatry 1997;5(1):7–17. [80] Hilty DM, Yellowlees PM, Nesbitt TS. Evolution of telepsychiatry to rural sites: changes over time in types of referral and in primary care providers’ knowledge, skills and satisfaction. Gen Hosp Psychiatry 2006;28(5):367–73. [81] Neufeld JD, Yellowlees PM, Hilty DM, et al. The e-mental health consultation service: providing enhanced primary-care mental health services through telemedicine. Psychosomatics 2007;48(2):135–41. [82] Oslin DW, Ross J, Sayers S, et al. Screening, assessment, and management of depression in VA primary care clinics. The Behavioral Health Laboratory. J Gen Intern Med 2006;21(1): 46–50.

INTEGRATING MENTAL HEALTH AND PRIMARY CARE

591

[83] Wagner EH, Austin BT, Von Korff M. Organizing care for patients with chronic illness. Milbank Q 1996;74(4):511–44. [84] Bodenheimer T, Wagner EH, Grumbach K. Improving primary care for patients with chronic illness. JAMA 2002;288(14):1775–9. [85] Bodenheimer T, Wagner EH, Grumbach K. Improving primary care for patients with chronic illness: the chronic care model, part 2. JAMA 2002;288(15):1909–14. [86] McEvoy P, Barnes P. Using the chronic care model to tackle depression among older adults who have long-term physical conditions. J Psychiatr Ment Health Nurs 2007;14(3):233–8. [87] Wagner EH, Glasgow RE, Davis C, et al. Quality improvement in chronic illness care: a collaborative approach. Jt Comm J Qual Improv 2001;27(2):63–80. [88] Unu¨tzer J, Katon W, Callahan CM, et al. Improving mood-promoting access to collaborative treatment. Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial. JAMA 2002;288(22):2836–45. [89] Schaefer J, Davis C. Case management and the chronic care model: a multidisciplinary role. Lippincotts Case Manag 2004;9(2):96–103. [90] Oxman TE, Dietrich AJ, Schulberg HC. The depression care manager and mental health specialist as collaborators within primary care. Am J Geriatr Psychiatry 2003;11(5):507–16. [91] Katon WJ, Von Korff M, Lin E, et al. Collaborative management to achieve depression treatment guidelines. J Clin Psychiatry 1997;58(Suppl 1):20–3. [92] Bower P, Gilbody S, Richards D, et al. Collaborative care for depression in primary care. Making sense of a complex intervention: systematic review and meta-regression. Br J Psychiatry 2006;189:484–93. [93] Gilbody S, Bower P, Fletcher J, et al. Collaborative care for depression: a cumulative metaanalysis and review of longer-term outcomes. Arch Intern Med 2006;166(21):2314–21. [94] Williams JW Jr, Gerrity M, Holsinger T, et al. Systematic review of multifaceted interventions to improve depression care. Gen Hosp Psychiatry 2007;29(2):91–116. [95] Rollman BL, Belnap BH, Mazumdar S, et al. A randomized trial to improve the quality of treatment for panic and generalized anxiety disorders in primary care. Arch Gen Psychiatry 2005;62(12):1332–41. [96] Bauer MS, McBride L, Williford WO, et al. Collaborative care for bipolar disorder: Part I., Intervention and implementation in a randomized effectiveness trial. Psychiatr Serv 2006; 57(7):927–36. [97] Bauer MS, McBride L, Williford WO, et al. Collaborative care for bipolar disorder: Part II. Impact on clinical outcome, function, and costs. Psychiatr Serv 2006;57(7):937–45. [98] Simon GE, Ludman EJ, Bauer MS, et al. Long-term effectiveness and cost of a systematic care program for bipolar disorder. Arch Gen Psychiatry 2006;63(5):500–8. [99] Simon GE, Ludman EJ, Unu¨tzer J, et al. Randomized trial of a population-based care program for people with bipolar disorder. Psychol Med 2005;35(1):13–24. [100] Callahan CM, Boustani MA, Unverzagt FW, et al. Effectiveness of collaborative care for older adults with Alzheimer disease in primary care: a randomized controlled trial. JAMA 2006;295(18):2148–57, zz. [101] Schoenbaum M, Miranda J, Sherbourne C, et al. Cost-effectiveness of interventions for depressed Latinos. J Ment Health Policy Econ 2004;7(2):69–76. [102] Simon GE, Von Korff M, Ludman EJ, et al. Cost-effectiveness of a program to prevent depression relapse in primary care. Med Care 2002;40(10):941–50. [103] Miranda J, Duan N, Sherbourne C, et al. Improving care for minorities: can quality improvement interventions improve care and outcomes for depressed minorities? Results of a randomized, controlled trial. Health Serv Res 2003;38(2):613–30. [104] Bruce ML, Ten Have TR, et al. Reducing suicidal ideation and depressive symptoms in depressed older primary care patients: a randomized controlled trial. JAMA 2004;291(9): 1081–91. [105] Harpole LH, Williams JW Jr, Olsen MK, et al. Improving depression outcomes in older adults with comorbid medical illness. Gen Hosp Psychiatry 2005;27(1):4–12.

592

THIELKE

et al

[106] Katon WJ, Schoenbaum M, Fan MY, et al. Cost-effectiveness of improving primary care treatment of late-life depression. Arch Gen Psychiatry 2005;62(12):1313–20. [107] Simon GE, Manning WG, Katzelnick DJ, et al. Cost-effectiveness of systematic depression treatment for high utilizers of general medical care. Arch Gen Psychiatry 2001;58(2):181–7. [108] Simon GE, Katon WJ, VonKorff M, et al. Cost-effectiveness of a collaborative care program for primary care patients with persistent depression. Am J Psychiatry 2001;158(10): 1638–44. [109] Grypma L, Haverkamp R, Little S, et al. Taking an evidence-based model of depression care from research to practice: making lemonade out of depression. Gen Hosp Psychiatry 2006;28(2):101–7. [110] Dietrich AJ, Oxman TE, Williams JW Jr, et al. Going to scale: re-engineering systems for primary care treatment of depression. Ann Fam Med 2004;2(4):301–4. [111] Asarnow JR, Jaycox LH, Duan N, et al. Effectiveness of a quality improvement intervention for adolescent depression in primary care clinics: a randomized controlled trial. JAMA 2005;293(3):311–9. [112] Nutting PA, Gallaher KM, Riley K, et al. Implementing a depression improvement intervention in five health care organizations: experience from the RESPECT-depression trial. Adm Policy Ment Health 2007;34(2):127–37. [113] Wells KB, Sherbourne C, Schoenbaum M, et al. Impact of disseminating quality improvement programs for depression in managed primary care: a randomized controlled trial. JAMA 2000;283(2):212–20. [114] Pincus HA, Pechura C, Keyser D, et al. Depression in primary care: learning lessons in a national quality improvement program. Adm Policy Ment Health 2006;33(1):2–15. [115] Cole SA, Farber NC, Weiner JS, et al. Double-disease management or one care manager for two chronic conditions: pilot feasibility study of nurse telephonic disease management for depression and congestive heart failure. Dis Manag 2006;9(5):266–76. [116] Meredith LS, Mendel P, Pearson M, et al. Implementation and maintenance of quality improvement for treating depression in primary care. Psychiatr Serv 2006;57(1):48–55. [117] Unu¨tzer J, Choi Y, Cook IA, et al. A web-based data management system to improve care for depression in a multicenter clinical trial. Psychiatr Serv 2002;53(6):671–3, 678. [118] Green CJ, Fortin P, Maclure M, et al. Information system support as a critical success factor for chronic disease management: Necessary but not sufficient. Int J Med Inform 2006; 75(12):818–28.

Prim Care Clin Office Pract 34 (2007) 593–610

Adult Post-Traumatic Stress Disorder: Screening and Treating in Primary Care Linda Nakell, PhD Family Practice Residency Program, Contra Costa Regional Medical Center, 2500 Alhambra Avenue, Martinez, CA 94553, USA

Post-traumatic stress disorder (PTSD) is the complex psychological response to extreme, life-threatening trauma that includes symptoms of re-experiencing the trauma, avoidance, and increased arousal. Patients who have PTSD are ‘‘stuck’’ in their trauma, ‘‘reliving it in thoughts, feelings, actions, or images’’ [1]. Primary care physicians frequently encounter patients suffering from the complex physical and mental manifestations of trauma and PTSD [2,3]. Doctors tend to be puzzled regarding treatment of these patients, and often consider them ‘‘difficult,’’ because their PTSD is undiagnosed and their PTSD-related somatic symptoms may not improve. Patients who have PTSD tend to be frightened and unhappy with their medical care [4]. Thus, both patients and physicians are dissatisfied with the management of PTSD and its somatic manifestations. This article summarizes recent literature in the area of PTSD and associated somatic complaints, and proposes an approach to caring for patients who have PTSD. An estimated 12% to 25% of patients seen in primary care have PTSD [2]. The cost of their care is twice as high as that of patients who do not have PTSD [5], and patients who have PTSD use the health care system significantly more often than other patients [3]. Patients who have PTSD visit doctors frequently and are treated for symptoms associated with PTSD, but too often they do not receive help for their underlying PTSD diagnosis. Patients who have PTSD present special challenges to the primary care physician. Their symptoms are often vague, complex, and difficult to interpret; their sensitivity to their symptoms and level of distress are high; and their underlying PTSD often has not been diagnosed. Patients who have PTSD are typically unaware of the connection between their past trauma and their current symptoms [3]. Most often, they leave without having their E-mail address: [email protected] 0095-4543/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pop.2007.05.010 primarycare.theclinics.com

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PTSD diagnosed, and frequently they return again and again with the same unresolved problems. PTSD has been called the ‘‘hidden diagnosis’’ in primary care [6]. Patients who have undiagnosed PTSD have somatic symptoms that may be unrelated to PTSD, exacerbated by PTSD, or may be the somatic expression of their mental health disorder. Whatever may be the cause of their symptoms, patients who have histories of trauma feel anxious and vulnerable in the world of health care. They have anxiety regarding somatic symptoms that often do not match a clear differential diagnosis, and they lack insight into the association between their symptoms and their trauma. They risk both not being taken seriously and losing control over what happens to their bodies, and yet they must turn to physicians for help with their symptoms. Patients who have undiagnosed PTSD, however, can benefit significantly from having their doctor diagnose their underlying disorder, and carefully and sensitively explain its association with their symptoms. When PTSD is identified, patients can seek the current psychopharmacological and psychological approaches to treatment of PTSD. Physicians who are aware of their patients’ PTSD can take this into consideration when planning invasive medical assessments and treatments, and can assist previously traumatized patients as they undergo the challenge of medical care. For all of these reasons, a high level of suspicion and screening for PTSD among primary care physicians is warranted. When discussing new diagnoses of PTSD and its association with physical symptoms, however, physicians should be careful not to blame patients for their symptoms. It can be helpful to normalize patients’ experiences, and to be aware of patients’ responses to information about PTSD. Discussing this over several visits, when possible, may limit patients’ distress (Table 1).

Epidemiology of post-traumatic stress disorder Post-traumatic stress disorder has been included as a diagnosis in the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) since 1980, but it has been known as a syndrome among soldiers long before under names such as ‘‘combat fatigue and ‘‘war neurosis.’’ American society has had remarkable resistance to acknowledging the severity of the impact of trauma, and people have tended to shun its victims [7,8]. More recently, research has addressed the epidemiology of trauma and PTSD in the general population, and the effects of trauma on health. Although a wealth of research since 1980 has addressed the epidemiology, pathophysiology, and treatment of PTSD, there is much yet to be learned, and 30% of patients still suffer from symptoms of PTSD as long as 10 years after the trauma [9]. Thus, PTSD can be a chronic disorder. Since the introduction of PTSD as a psychiatric diagnosis, the definition of the signal traumatic event has changed, but the characteristic symptoms

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Table 1 Guidelines for working with PTSD patients Asking about trauma:

Asking about symptoms of PTSD:

Assessing for current danger: If yes, insure safety. If no, see below. Making PTSD diagnosis and connection with current symptoms:

At end of visit, inquire about safety:

Because so many of my patients have had traumatic experiences, I generally ask people if they have ever experienced an event that was life-threatening to them or someone else.  Has that ever happened to you?  Have you ever had an experience where you feared for your safety or the safety of someone else?  Have you ever been physically, sexually or emotionally harmed? During the past month, have you:  had disturbing thoughts or images of the trauma or nightmares?  lost interest in things or felt numb?  avoided certain people, places, or situations that remind you of the experience?  felt jumpy, on guard, or easily startled?  had difficulty getting along with people, such as friends, family or coworkers? Are any of these dangerous situations continuing in your life now? Some people who have had extremely frightening experiences (especially when they have occurred over a long period of time) develop symptoms like you have. We call this post-traumatic stress disorder. It can help to have a name to help you understand that many people like you who have had traumatic experiences also have symptoms of (chronic pain, pelvic pain, headache or other symptom the patient is experiencing). Have you ever thought that there might be a connection between your traumatic experience and your symptoms? We’ve discussed a lot of things that could be upsetting. I’m wondering how you’re going to feel, and how you’re going to take care of yourself after you leave my office today.

have endured. In DSM-III, the traumatic event was required to be ‘‘outside the range of usual human experience.’’ At least 60% of women and 50% of men are exposed to a traumatic event during their lifetimes [9], however, so such events are not outside usual human experience. In fact, they are part of the human condition. In the DSM-IV, therefore, the definition of the signal traumatic event was changed to one involving ‘‘actual or threatened death or serious injury, or a threat to the physical integrity of self or others’’ [10], and in which the

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person’s response must include ‘‘intense fear, helplessness, or horror.’’ The three principal symptoms of PTSD include: (1) re-experiencing the event (in flashbacks, dreams, or distress at cues that resemble the event), (2) avoidance and numbing (avoiding remembering, inability to remember the event, feelings of detachment, diminished interest in activities, or a sense of a foreshortened future), and (3) increased arousal (sleep disturbance, irritability, difficulty concentrating, hypervigilance, or startling easily). Traumatic events leading to PTSD include military combat, natural and man-made disasters, motor vehicle accidents, rape, violent personal assault, receiving a diagnosis of a life-threatening disease, childhood abuse (sexual and physical), and medical procedures. In addition, medical conditions and interventions, including myocardial infarction [11,12], surgical trauma [13], treatment for peritonitis [14], burn treatment [15,16], and the experience of cancer [17,18], can be traumatic experiences and contribute to PTSD. Although an estimated 50% to 60% of the US population experiences a traumatic event, most people exposed to trauma do not develop PTSD. The National Comorbidity Survey (NCS) studied over 8000 adults in the United States, and found that among people who had been exposed to trauma, 7.8% developed PTSD. Women developed PTSD at twice the rate of men (10.4% versus 5%, P!.05) [9]. The traumas most likely to lead to PTSD among men were rape, combat exposure, and childhood neglect and physical abuse, and among women they were rape, sexual molestation, physical attack, being threatened with a weapon, and childhood physical abuse. It appears that the experience of an impersonal trauma, such as a natural disaster, is less likely to contribute to PTSD. Women, however, were more likely to have experienced one of these ‘‘high-impact’’ interpersonal traumas, and they were more likely to experienced PTSD as a result of that exposure. Traumatic experiences leading to PTSD range from discrete, singular events, such as traffic accidents, rape, or robbery, to generally time-limited experiences, such as war-related combat or political torture, to experiences that endure over time and are deeply embedded in a person’s personal relationships, such as childhood neglect or abuse, or intimate partner violence. Most people who experience one trauma report having experienced more than one. Accordingly, there is a range of severity and persistence of PTSD and its comorbid symptoms. It is essential that primary care physicians understand assessment and primary care treatment of patients who have PTSD. Trauma has a powerful impact on health and health-related behaviors, patients use primary care for treatment of mental illness and PTSD, and patients who have histories of trauma disproportionately use the health care system. Acute stress disorder Acute Stress Disorder (ASD) is defined in DSM-IV as symptoms of reexperiencing, avoidance, and hyperarousal occurring within a month after

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a traumatic experience [10]. It is important for physicians to address symptoms of ASD, however, because 60% to 80% of patients who have ASD will develop PTSD [19]. Subthreshold post-traumatic stress disorder Patients in primary care who have had traumatic experiences may not meet DSM-IV criteria for PTSD, and yet may have some of the symptoms of PTSD [20,21]. Some of these patients may be recovering from full PTSD [22]. These patients who have ‘‘subthreshold’’ PTSD have physical and mental impairment associated with their trauma [23], are at increased risk for suicidal ideation, and benefit from treatment of their physical and mental symptoms in the context of their history of trauma. Complex post-traumatic stress disorder Clinicians have identified a syndrome called ‘‘complex PTSD,’’ which is not adequately addressed by the DSM-IV diagnosis. Victims of prolonged, repeated trauma, especially in childhood, have symptoms beyond those of PTSD. These include disruptions in affect regulation, dissociation and changes in consciousness, changes in self-perception, altered perception of the perpetrator, disruptions in relationships with others, and hopelessness or loss of meaning [1,7]. These patients have difficulty with self-regulation, and with forming and maintaining relationships, including those with physicians. They may be self-injurious, suicidal, explosively angry, and selfblaming, and they may alternate in the quality of their relationships to their physicians, from desiring extreme closeness and disclosure to mistrust, distance, and anger [7]. Patients who have borderline personality disorder have a high incidence of severe physical and sexual abuse, and many borderline symptoms may be sequelae of trauma. Thus, patients who have histories of severe trauma may be mislabeled as having borderline personality disorder [24]. Biological underpinnings of post-traumatic stress disorder Trauma contributes to changes in brain structure and function, as well as to changes in the hypothalamic-pituitary-adrenocortical (HPA) axis and the immune system. These changes, and the relationship between trauma and brain development, are highly complex and are actively being studied. Changes in brain structure and physiology have been found in people who have PTSD. The hippocampus, which processes and stores information and then helps the person evaluate current threats by comparing them with previous experiences, has a smaller volume in people who have PTSD [25]. The amygdala, which mediates arousal, is hyperactive, likely leading to the heightened startle response in people who have PTSD [25]. In addition, the adrenergic and sympathetic nervous systems are more reactive in patients

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who have PTSD. Whereas the normal response to stress is to increase cortisol production, people who have PTSD have lower levels of cortisol in response to stress [26]. Overall, it appears that people who have PTSD do not return to normal levels of arousal when stress is removed [24]. Association between post-traumatic stress disorder and medical morbidity Both research evidence and clinical experience lead to the conclusion that trauma and PTSD are associated with significant impairments in both physical and mental health. Studies have found exposure to trauma associated with poor quality of self-reported health and both subjective and objective indicators of health problems, including chronic pain, irritable bowel syndrome, arthritis, and fibromyalgia [27]. The Adverse Childhood Experience (ACE) study [28,29], for example, was an extensive survey of 9500 adult members of a health maintenance organization. They found that adults who reported four or more types of adverse childhood experiences, such as childhood abuse and household dysfunction (with a family member in prison, with violence against the mother, with a substance abuser, or with a chronically mentally ill or depressed family member), were more likely to report chronic illnesses, as well as negative health behaviors and depression. These chronic diseases included bronchitis or emphysema, stroke, cancer, and ischemic heart disease. The members who had adverse childhood experiences tended to rate their health status as fair or poor. The health risks and negative health behaviors, such as smoking and substance abuse, increased with the number of adverse childhood experiences reported in this large sample. A detailed study of 7000 male veterans, the Vietnam Experience Study, found that those who served in Vietnam reported more current use of prescription drugs and more disease, somatic symptoms, and fertility problems, than those who did not serve in Vietnam. These self-report data were corroborated by objective data showing hearing loss, occult blood in the stool, history of hepatitis B infection, and lower sperm counts among the Vietnam veterans. Also, there was a 17% higher rate of mortality among Vietnam veterans than among veterans who were not exposed to combat, mostly because of accidental deaths soon after discharge. Several studies of veterans, both from Vietnam and the Persian Gulf War, found that those who had PTSD self-reported more physical symptoms, medical conditions in various organ systems, and health-related functioning [30,31]. Other studies have found that exposure to war-related stressors was associated with increased mortality and with deaths related to cardiovascular disease over 10 years [32]. Diagnosed PTSD has also been linked to poor health outcomes. In the Centers for Disease Control (CDC) Vietnam Experience Study [30], veterans who had diagnosed PTSD were at increased risk relative to veterans who did not have PTSD for chronic disorders, including circulatory, digestive, musculoskeletal, endocrine, and respiratory disorders. PTSD is associated with

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medical morbidity in studies of both civilians and veterans, even beyond that accounted for by depression. The combination of PTSD and other psychiatric disorders (depression, substance abuse, and hypochondriasis) is most strongly related to medical problems [33]. Another study of Vietnam veterans found that those who had PTSD had increased prevalence of autoimmune diseases, including rheumatioid arthritis, psoriasis, insulin-dependent diabetes, and thyroid disease, and that they had measurable immune system changes when compared with veterans who did not have PTSD [34]. Important associations between chronic pain and PTSD have been found, and Asmundson and colleagues [35] describe both PTSD in patients who had chronic pain, and chronic pain in patients who had PTSD. They say that between 10% and 50% of chronic pain patients meet criteria for PTSD, and they emphasize that treatment for either chronic pain or PTSD should include assessment for the other disorder [35]. Clinical experience also suggests the connection between a history of trauma and negative health behaviors and health status. Experienced clinicians are aware of the association between patients’ history of trauma and substance abuse, tobacco use, chronic pain, somatization, and inconsistent follow-though with medical care. Risk-factors for post-traumatic stress disorder Among individuals who experience trauma, the risk of developing PTSD is related to numerous factors, including younger age at the time of trauma, more chronic, ongoing trauma, the nature of the trauma (with interpersonal traumas most likely to lead to PTSD) [36], the individual’s prior history of trauma [37], less social support, family psychiatric history, lower socioeconomic status, and the initial severity of reaction to the traumatic event. There has been discussion of the role of the victim’s degree of dissociation at the time of the trauma in the development of PTSD. Dissociation occurs when a person experiences a feeling of detachment from his emotional condition or body, sometimes in a dreamlike state. The extent of the dissociative response during the event (peritraumatic dissociation), the extent to which victims felt that their lives were at risk during the event, and the intensity of the emotional response during and immediately after the event have been associated with PTSD. This is controversial, however, because several studies have shown that persistent dissociation after the traumatic event was a better predictor of PTSD [38,39]. Thus, it may be that persistent, longerterm dissociation is more important than dissociation at the time of the trauma in the development of PTSD [19]. Presentation Patients who have PTSD are coping with intrusive memories, hyperarousal, and avoidance, all of which interfere with daily life. Most of

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them suffer from psychiatric comorbidities, including depression, anxiety, and substance abuse [7]. Many patients use alcohol and drugs to selfmedicate PTSD symptoms. One of the most distressing symptoms of PTSD is disturbed sleep [24]. Often, patients who have PTSD have heightened sensitivity to physical distress, and they may have chronic pain and somatization. Patients who identify the role of trauma in their lives may say that they are just not the people they were before their traumatic experience, that they are generally more withdrawn and fearful. In a study of over 700 primary care patients, Samson and colleagues [3] found that patients who had PTSD were more likely to complain of somatic symptoms, such as musculoskeletal, gastrointestinal (GI), and neurological symptoms, than of depression or anxiety. Patients are likely to bring physical, rather than mental, complaints to primary care doctors as their presenting symptoms, even when they have important concerns about mental symptoms. Given that patients who have PTSD are at increased risk for various diseases, including GI, vascular and cardiac, immune system, and lung disorders, and they are likely to have risky health behaviors such as tobacco and substance abuse, it is wise to consider the trauma history of many patients seen in primary care. Working with traumatized patients presents special challenges. They may respond to minor traumas, such as relatively minor auto accidents, with symptoms that are beyond those expected by the circumstances of the current trauma [40]. Patients who have PTSD may have a difficult time following through with treatment recommendations, be unusually sensitive to medicines, or have anxiety related to medical tests and treatment options, including medicines. Patients who have a history of abusive, controlling relationships may behave with their physicians in ways that inspire some doctors to control them in paternal (or parental) relationships. Thus, it may be difficult for doctors to establish a workable therapeutic alliance with such patients. Paternal behavior on the part of the physician is generally less useful than sharing the responsibility for care with such patients, for whom it is therapeutic to gradually assume more control over their lives as they learn about their PTSD and as their symptoms improve. Barriers to asking about post-traumatic stress disorder As mentioned earlier, society in general and the field of medicine in particular have been aware of the effects of trauma for generations, but have preferred to avoid, disregard, or dismiss the effects of trauma [7,8]. For these and other reasons, it is easy for physicians to overlook the diagnosis of PTSD in clinical practice. Primary care physicians have identified lack of confidence in identification and management skills, fear of offending patients by asking about prior trauma, and lack of time as barriers to asking about domestic violence [41]. Primary care physicians have shown reluctance to assess for other mental health disorders, such as depression, and

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have in general preferred to avoid seeing patients who have mental health problems. It is often uncomfortable to hear patients’ stories of trauma, and physicians who hear about trauma risk themselves becoming victims of vicarious trauma [42,43]. In addition, during this era of extreme time pressures in medical care, physicians may fear that addressing PTSD will demand too much time [3]. Why assess for trauma and post-traumatic stress disorder in primary care? A survey of primary care patients found that three fourths of them supported doctors routinely questioning patients about prior physical abuse, and almost that many wanted their physicians to inquire about prior sexual abuse [44]. Survivors of abuse also have said that they appreciate being asked about their trauma histories, especially if the doctor validates the patient’s experience in a non-blaming manner [45]. Thus, patients want their doctors to be concerned about their history of trauma. Primary care physicians, however, do not routinely screen for abuse [46,47]. Asking patients about their trauma history can be useful to patients in several ways. First, when patients acknowledge their history of trauma, the physician can provide psycho-education to help patients understand their trauma and its effects, and then can recommend potentially useful treatment. Second, physicians who understand patients’ histories of trauma can appreciate patients’ symptoms and fears in context, and therefore treat patients with appropriate care. Guidelines for working with traumatized patients are described below and in Table 1. Finally, patients may not be ready to acknowledge their history of trauma to themselves or their physicians. The experience of having been asked about this history, however, can change how they think about their own experience, and may lead to a more open discussion of their trauma in the future. For patients who have undiagnosed PTSD, understanding the diagnosis and the relationship between trauma and the distress they experience is the first step toward health. How to assess for trauma and post-traumatic stress disorder Patients who have PTSD feel vulnerable and frightened, and they need to perceive an environment as safe to disclose their trauma history [7,24]. They may be afraid of being blamed, shunned, or considered ‘‘crazy,’’ or they may fear that the doctor’s inquiry will arouse trauma-related flashbacks. Therefore, the physician’s openness and receptivity to the patient’s experience is therapeutic, and the physician and should express appreciation for the patient’s disclosure (‘‘I’m glad that you were able to talk about this today’’) and empathic support, such as ‘‘I’m sorry you’ve been having such terrible nightmares (or insert other symptom here).’’ Although there are various psychological assessment tools for PTSD, the Short Screening Scale for PTSD [48] is brief and has been tested in

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a primary care setting. The self-report test asks patients about ever having had an experience that was so frightening, horrible, or upsetting that in the past month they have certain symptoms. Patients who respond positively to four of seven symptoms are considered to have PTSD. Alternatively, the physician can screen the patient verbally (see Table 1). Normalizing the patient’s experience before asking questions about trauma or reviewing positive results of the self-report measure can help traumatized patients feel more comfortable revealing their trauma history (eg, ‘‘At some point in their lives, many people have had experiences that were extremely distressing or frightening.’’). It is best to ask a general question first, such as, ‘‘Have you ever experienced an event that was life-threatening to you or someone else? Have you ever encountered an event where you feared for your safety or the safety of someone else? Have you ever experienced an event that deeply frightened you and left you feeling shocked or helpless?’’ followed by a question about abuse such as ‘‘Have you ever been physically, sexually, or emotionally harmed?’’ Some patients are more likely to report having been afraid or upset than having been abused [12]. When the response to one of these questions is positive, the physician can follow up with questions regarding PTSDrelated symptoms, including  Disturbing thoughts or images of the trauma or nightmares  Loss of interest in things or feeling numb  Avoidance of certain people, places, or situations that remind patients of the experience  Feeling jumpy, on guard, or easily startled  Difficulty getting along with people, such as friends, family, or coworkers It is essential to assess whether the traumatic experiences are ongoing or in the past by asking, ‘‘Are any of these dangerous or life-threatening experiences are still continuing in your life now?’’ Patients are not likely to report current abuse, however, in the presence of the perpetrator, because of fears of retribution. If the trauma is current abuse, the physician must assess if mandated reporting is required, and should inform the patient of the limits of confidentiality. The physician should express concern and empathy, and inform the patient that help is available. The National Domestic Violence Hotline can provide local resources 24 hours a day: 1-800-799-SAFE or TTY 1-800787-3224. It is important to ensure that the patient will be safe when she leaves the clinic. Except in the case of minors, for whom reporting is mandated, the physician should avoid controlling traumatized patients by demanding that they seek help, but should clearly make resources available. Patients in currently abusive relationships may not be ready to change their living situations immediately, but should know that resources are available whenever they are ready.

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When abuse is not ongoing, the physician should express empathy, and then describe PTSD (see Table 1): ‘‘Some people who have had extremely frightening experiences (especially when they have occurred over a long period of time) develop symptoms like the ones you describe. We call this post-traumatic stress disorder. It can help to have a name to attach to what you have been feeling, and to understand that we know that these symptoms frequently are associated with the kind of stressful experience you have had.’’ The physician can then explain the potential connection between the presenting symptoms and PTSD: ‘‘Many people who have had traumatic experiences like you have also have symptoms of (chronic pain, pelvic pain, or other symptom the patient is experiencing). Have you ever thought that there might be a connection between your traumatic experience and your symptoms?’’ Patients who have PTSD, especially if they dissociate, often fear that they are ‘‘crazy.’’ As PTSD is explained, it is important to remind patients that they are not crazy, but that their symptoms are common manifestations of trauma and PTSD. Some patients, however, may not immediately accept the connection between their distress and their history of trauma. It is best not to elicit details of the patient’s traumatic experience at this early point for several reasons: (1) physicians in primary care usually do not have sufficient training or time for a therapeutic exploration of the trauma; (2) disclosure of the trauma can be re-traumatizing for patients, and so must be done with much care and skill; and (3) disclosure of the trauma usually should take place very gradually, along with support of the patient’s strengths for coping with this disclosure, to avoid exacerbating PTSD symptoms. Special considerations in medical treatment of post-traumatic stress disorder Patients who have PTSD have been traumatized and are fearful. Many of them have experienced loss of control over their lives and their bodies, and they are suffering. They are highly sensitive to physical sensations and to loss of personal control, and yet they want relief from their symptoms. Patients may be ambivalent about their medical treatment, and may request or agree to testing or treatment at one visit and refuse it at the next visit. For these reasons, physicians should be aware of patients’ concerns with regard to medical evaluations, and should be willing to work with patients’ ambivalence. Examinations can remind some patients of traumatic events, and can trigger flashbacks and other symptoms of PTSD. Therefore, it is important to keep a safe personal distance when interviewing patients who have trauma histories. Before any physical examination or procedure, explain what you are going to do and why, and ask the patient’s permission before touching him or her to reduce traumatization or agitation. Be aware that any internal examination, including mouth, throat, and pelvic examinations, may be especially frightening to patients who have certain trauma histories.

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When patients must undress for an examination, it is important to allow them to dress themselves before discussing results or plans. A patient’s sense of personal safety may be more acutely important to him than invasive preventive care, such as pap smears or colonoscopies. The timing of such examinations should be discussed with the patient. Patients’ fear and ambivalence about procedures may result in their missing appointments or arriving for a procedure under the influence of alcohol or drugs. Physicians can supportively tell patients that if they have reservations about undergoing a procedure, they can contact the physician to discuss their concerns, or can reschedule for another time when they may have more information or are more comfortable. In this way, patients can feel more in control of their medical treatment, and can avoid feeling that they have let their physician down, which can severely disrupt the physician-patient relationship. Patients who have PTSD generally lack the ability to manage anxiety and to soothe themselves. Following medical visits during which patients have discussed their trauma or undergone stressful medical examinations or treatment, their PTSD symptoms of anxiety and re-experiencing their trauma can escalate, leading at times to self-destructive behavior. Therefore, it is advisable to inquire how patients will take care of themselves after they leave the physician’s office (see Table 1). This provides an opportunity for physicians to assess the patient’s safety and to recommend self-care, such as doing something enjoyable and self-soothing, or finding a way to be with others when being alone presents risks to the patient. General approach to treatment of post-traumatic stress disorder Most adults who have PTSD benefit from a combination of treatment approaches, including primary care treatment that is sensitive to the patient’s trauma-related medical issues, psychotherapy, and psychopharmacological treatment. Whereas most patients who have PTSD recover, many others improve over time but remain symptomatic. Because no single intervention is curative, treatment combinations may be most helpful in managing PTSD [49]. Patients who have PTSD need a relationship over time with a primary care physician who is sensitive to their needs. Treatment of post-traumatic stress disorder: psychopharmacology No medicine has yet been proven to be effective in preventing or curing PTSD, but psychopharmacological approaches can help patients reduce PTSD symptoms [24]. Research on psychopharmacological treatment of PTSD, however, lags severely behind that for treatment of depression [50]. Clinicians may feel pressured by patients’ anxiety and distress to treat patients’ PTSD symptoms urgently, changing medicines frequently until a solution is found. It is advisable, though, to work with patients carefully

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over time, using the physician-patient relationship to help patients tolerate medicines and to undergo adequate trials before making changes. Patients who have PTSD can be highly sensitive to physical symptoms and therefore to medication side effects. For this reason, adherence to medicine may be increased when patients who have PTSD start at low doses and gradually increase their dose. Patients’ trust and adherence are maximized when physicians ask patients about their experience with the medication’s effectiveness and side effects during follow-up visits, and when patients feel that physicians believe and work with their perceptions of their medicine. Selective seratonin-reuptake inhibitors (SSRIs) are recommended as the first treatment for PTSD by psychiatric consensus groups who have reviewed psychopharmacological approaches to PTSD [51–53]. The SSRIs may reduce the core symptoms of PTSD of re-experiencing, avoidance/ numbness, and hyperarousal. SSRI treatment is most helpful in the long term if it is continued for 9 to 12 months after symptom remission [24,54]. After 4 to 6 weeks, patients who have a partial response to the initial SSRI require an individualized approach with additional symptom-related medicine. Specifically, patients with persistent insomnia or nightmares may be given a sedating antidepressant, such as trazodone, or another nonaddictive sleep remedy; patients who have comorbid psychosis may be treated with an antipsychotic; and patients who have bipolar spectrum disorder may be given a mood stabilizer or an antipsychotic. There is, however, potential severe weight gain associated with some second generation (atypical) antipsychotics, especially olanzapine [55]. When patients do not respond to the initial SSRI, they may switch to another SSRI. In addition, International Psychopharmacology Algorithm Project (IPAP) recommends that sleep disorders be treated with lifestyle modification (reducing caffeine, assessing over-the-counter medication use, and behavior therapy, such as imagery rehearsal therapy) [56]. Benzodiazepines may reduce anxiety and promote sleep, but patients who have PTSD who are prone to addiction may abuse or become dependent on them [55]. Primary care physicians may refer patients who do not respond to antidepressants for psychiatric care, when it is available. Two small studies have suggested that PTSD may be prevented with the beta-blocker propanolol given immediately after the trauma [57,58], but most reviewers think the evidence of its usefulness is too limited to recommend its use [51]. Interested readers can find a comprehensive and thoughtful review of PTSD psychopharmacology by psychiatrist Catherine Scott in Principles of Trauma Therapy: A Guide to Symptoms, Evaluations, and Treatment [24]. Treatment of post-traumatic stress disorder: psychotherapy The outcome of psychotherapy appears to depend more on the quality of the therapeutic relationship than the specific technique used [24]. Cognitive

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behavioral therapy, however, has been most extensively studied among PTSD patients. Cognitive behavioral therapy provides a supportive environment in which patients can remember their traumatic experiences in manageable doses, along with learning adaptive, symptom-related coping skills [59]. Coping skills include relaxation training, stress management, activity scheduling, cognitive reframing, and positive self-talk [59]. Patients learn to soothe themselves, and can begin to tolerate anxiety and other PTSD symptoms as they gradually view their anxiety as less dangerous, and can also begin to find meaning in their experiences [24]. Another approach with positive outcome studies is eye movement desensitization and reprocessing (EMDR) [60]. In this information-processing therapy, the client repeatedly focuses on a traumatic image, negative thought, and body sensations while simultaneously focusing on an external stimulus, such as moving his eyes following the therapist’s fingers as they move back and forth across his field of vision [61]. Recent meta-analyses of randomized controlled trials found that psychological treatment for PTSD should be trauma-focused, rather than addressing stress management in general [62], and that patients recover or improve [63]. Dialectical behavior therapy addresses the needs of patients who have complex PTSD, and teaches them approaches to mindfulness meditation that have been helpful. These therapies can help patients review their trauma, cognitively reconstruct [59] their condition in a more positive light, and develop skills for coping with symptoms. Research addresses short-term psychotherapy and short-term improvements. Patients who have chronic or complex PTSD, comorbid substance abuse, or other comorbid psychiatric problems may require treatment addressing their comorbidities over a longer period. In addition, families of patients who have PTSD are strongly affected, and their needs should be addressed in psychotherapy. Vicarious trauma: taking care of the caregiver Working with patients who have PTSD, hearing their stories of trauma, contributes to the emotional distress of care providers, referred to as ‘‘vicarious traumatization’’ [42], ‘‘traumatic countertransference’’ [7], or ‘‘compassion fatigue’’ [64]. Psychiatrist Judith Herman says clearly in Trauma and Recovery, ‘‘Trauma is contagious’’ [7]. Physicians working with trauma survivors may find themselves feeling hopeless, and avoiding patients’ tales of trauma or becoming over-involved in their attempts to rescue traumatized patients [43], and they may reverberate between these two extremes. Working with traumatized patients can reignite traumatic memories for the many physicians who have personal or family histories of trauma. Physicians may distance themselves emotionally from their traumatized patients by blaming the patients for their victimization or by using dark humor. The daily exposure to very sick patients and people in crisis experienced in primary care

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medicine can itself be traumatizing, and physicians may develop symptoms of PTSD, including nightmares, flashbacks, startle responses, avoiding people or activities, feeling angry or sad, overeating, or drinking too much alcohol [47]. For these reasons, it is especially important for physicians to actively and intentionally engage in self-care activities [47,65]. These include developing self-awareness of personal responses, reducing isolation by consulting with colleagues, maintaining rewarding or relaxing activities outside of work, and finding meaning and resilience in the healthy aspects of patients’ stories. Summary Trauma and PTSD affect patients’ physical health and daily functioning. Primary care physicians should remember to screen for trauma history and symptoms of PTSD when patients present with somatization, chronic pain, or other unexplained symptoms. Patients can benefit from learning about the relationship between their symptoms and their trauma, which should be explained carefully over time. Perceived loss of control during physical examinations and procedures may be frightening, and physicians should ask patients’ permission before touching them. Patients who have PTSD benefit from treatment, including both psychopharmacology (primarily SSRIs) and psychotherapy. Finally, hearing patients’ stories of trauma and exposure to very sick patients can be traumatizing for physicians, who are encouraged to actively engage in self-care activities. Acknowledgments The author wishes to thank John Echols, MD, Patricia Hennigan, PhD, Barry Miller, MD, and Patricia Reed, PhD for comments on earlier drafts of this paper.

References [1] van der Kolk B, McFarlane AC, van der Hart O. A general approach to treatment of posttraumatic stress disorder. In: van der Kolk B, McFarlane AC, Weisaeth L, editors. Traumatic stress: the effects of overwhelming experience on mind, body, and society. New York: Guilford Press; 2006. p. 417–40. [2] Stein MB, McQuaid JR, Pedrelli P, et al. Posttraumatic stress disorder in the primary care medical setting. Gen Hosp Psychiatry 2000;22:261–9. [3] Samson AY, Bensen S, Beck A, et al. Posttraumatic stress disorder in primary care. J Fam Pract 1999;48:222–7. [4] van Zelst WH, de Beurs E, Beekman AT, et al. Well-being, physical functioning, and use of health services in the elderly with PTSD and subthreshold PTSD. Int J Geriatr Psychiatry 2006;21:180–8. [5] Koss MP, Koss PG, Woodruff WJ. Deleterious effects of criminal victimization on women’s health and medical utilization. Arch Intern Med 1991;151:342–7.

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[6] Lecubrier Y. Posttraumatic stress disorder in primary care: a hidden diagnosis. J Clin Psychiatry 2004;65:49–54. [7] Herman J. Trauma and recovery. New York: Basic Books; 1992. [8] van der Kolk BA, Weisaeth L, van der Hart O. History of trauma in psychiatry. In: van der Kolk BA, McFarlane AC, Weisaeth L, editors. Traumatic stress: the effects of overwhelming experience on mind, body, and society. vol. 1. New York: Guilford Press; 2007. p. 47–76. [9] Kessler RC, Sonnega A, Bromet E, et al. Posttraumatic stress disorder in the national comorbidity survey. Arch Gen Psychiatry 1995;52:1048–60. [10] American Psychiatric Association, American Psychiatric Association. Task force on DSM-IV. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th (text revision) edition. Washington, DC: American Psychiatric Association; 2000. [11] Doerfler LA, Pbert L, DeCosimo D. Symptoms of posttraumatic stress disorder following myocardial infarction and coronary artery bypass surgery. Gen Hosp Psychiatry 1994;16: 193–9. [12] Doerfler LA, Paraskos JA, Piniarski L. Relationship of quality of life and perceived control with posttraumatic stress disorder symptoms 3 to 6 months after myocardial infarction. J Cardiopulm Rehabil 2005;25:166–72. [13] Holbrook TL, Anderson JP, Sieber WJ, et al. Outcome after major trauma: 12-month and 18-month follow-up results from the trauma recovery project. J Trauma 1999;46:765–71, [discussion 771–3]. [14] Boer KR, Mahler CW, Unlu C, et al. Long-term prevalence of posttraumatic stress disorder symptoms in patients after secondary peritonitis. Crit Care 2007;11:R30. [15] Saxe GN, Stoddard F, Hall E, et al. Pathways to PTSD, Part I: Children with burns. Am J Psychiatry 2005;162:1299–304. [16] Hall E, Saxe G, Stoddard F, et al. Posttraumatic stress symptoms in parents of children with acute burns. J Pediatr Psychol 2006;31:403–12. [17] Kornblith AB, Herndon JE 2nd, Weiss RB, et al. Long-term adjustment of survivors of early-stage breast carcinoma, 20 years after adjuvant chemotherapy. Cancer 2003;98: 679–89. [18] Hegel MT, Moore CP, Collins ED, et al. Distress, psychiatric syndromes, and impairment of function in women with newly diagnosed breast cancer. Cancer 2006;107:2924–31. [19] Peleg T, Shalev AY. Longitudinal studies of PTSD: overview of findings and methods. CNS Spectr 2006;11:589–602. [20] Marshall RD, Olfson M, Hellman F, et al. Comorbidity, impairment, and suicidality in subthreshold PTSD. Am J Psychiatry 2001;158:1467–73. [21] Grubaugh AL, Magruder KM, Waldrop AE, et al. Subthreshold PTSD in primary care: prevalence, psychiatric disorders, healthcare use, and functional status. J Nerv Ment Dis 2005;193:658–64. [22] Zlotnick C, Rodriguez BF, Weisberg RB, et al. Chronicity in posttraumatic stress disorder and predictors of the course of posttraumatic stress disorder among primary care patients. J Nerv Ment Dis 2004;192:153–9. [23] Zlotnick C, Franklin CL, Zimmerman M. Does ‘‘subthreshold’’ posttraumatic stress disorder have any clinical relevance? Compr Psychiatry 2002;43:413–9. [24] Briere J, Scott C. Principles of trauma therapy: a guide to symptoms, evaluations, and treatment. Thousand Oaks (CA): Sage Publications; 2006. [25] Rauch SL, Shin LM, Phelps EA. Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging researchdpast, present, and future. Biol Psychiatry 2006; 60:376–82. [26] van der Kolk BA. The body keeps the score: approaches to the psychobiology of posttraumatic stress disorder. In: van der Kolk BA, McFarlane AC, Weisaeth L, editors. Traumatic stress: the effects of overwhelming experience on mind, body, and society. New York: Guilford Press; 2007. p. 214–41.

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[27] Dobie DJ, Kivlahan DR, Maynard C, et al. Posttraumatic stress disorder in female veterans: association with self-reported health problems and functional impairment. Arch Intern Med 2004;164:394–400. [28] Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. the adverse childhood experiences (ACE) study. Am J Prev Med 1998;14:245–58. [29] Edwards VJ, Anda RF, Felitti VJ, et al. Adverse childhood experiences and health-related quality of life as an adult. In: Kendall-Tackett KA, editor. Health consequences of abuse in the family: a clinical guide. Washington, DC: American Psychological Association; 2004. p. 81–94. [30] Boscarino JA. Diseases among men 20 years after exposure to severe stress: implications for clinical research and medical care. Psychosom Med 1997;59:605–14. [31] Barrett DH, Doebbeling CC, Schwartz DA, et al. Posttraumatic stress disorder and selfreported physical health status among U.S. military personnel serving during the gulf war period: a population-based study. Psychosomatics 2002;43:195–205. [32] Sibai AM, Fletcher A, Armenian HK. Variations in the impact of long-term wartime stressors on mortality among the middle-aged and older population in Beirut, Lebanon, 1983–1993. Am J Epidemiol 2001;154:128–37. [33] Schnurr PP, Green BL. Understanding relationships among trauma, prosttraumatic stress disorder, and health outcomes. In: Schnurr PP, Green BL, editors. Trauma and health: physical health consequences of exposure to extreme stress. Washington, DC: American Psychological Association; 2004. p. 247–74. [34] Boscarino JA. Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies. Ann N Y Acad Sci 2004;1032:141–53. [35] Asmundson FJF, Coons MJ, Taylor ST, et al. PTSD and the experience of pain: research and clinical implications of shared vulnerability and mutual maintenance models. Can J Psychiatry 2002;10:930–7. [36] Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry 2000;61(Suppl 5):4–12, [discussion 13–4]. [37] Breslau N, Chilcoat HD, Kessler RC, et al. Previous exposure to trauma and PTSD effects of subsequent trauma: results from the Detroit Area Survey of Trauma. Am J Psychiatry 1999; 156:902–7. [38] Briere J, Scott C, Weathers F. Peritraumatic and persistent dissociation in the presumed etiology of PTSD. Am J Psychiatry 2005;162:2295–301. [39] Murray J, Ehlers A, Mayou RA. Dissociation and post-traumatic stress disorder: two prospective studies of road traffic accident survivors. Br J Psychiatry 2002;180: 363–8. [40] Sugg N, Inui T. Opening Pandora’s box: primary care physicians’ response to domestic violence. JAMA 1992;267:3157–60. [41] Sugg NK, Thompson RS, Thompson DC, et al. Domestic violence and primary care: attitudes, practices and beliefs. Arch Fam Med 1999;8:301–6. [42] McCann IL, Pearlman LA. Vicarious traumatization: a framework for understanding the psychological effects of working with victims. J Trauma Stress 1990;48:232–49. [43] Meichenbaum D. Helping the helpers. In: Scott MJ, Palmer S, editors. Trauma and posttraumatic stress disorder. London: Cassell; 2000. p. 117–21. [44] Friedman LS, Samet JH, Roberts, et al. Inquiry about victimization experiences: a survey of patient preferences and physician practicies. Arch Intern Med 1992;152: 1186–90. [45] Gerbert B, Abercrombie P, Caspers N, et al. How health care providers help battered women: the survivor’s perspective. Women Health 1999;29:115–35. [46] Rodriguez MA, Bauer HM, McLoughlin E, et al. Screening and intervention for intimate partner abuse: practices and attitudes of primary care physicians. JAMA 1999;282: 468–74.

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[47] National Center for Posttraumatic Stress Disorder. Trauma, PTSD, and the primary care provider. Available at: http://www.ncptsd.va.gov/ncmain/ncdocs/fact_shts/fs_primary_care. html?opm¼1&rr¼rr98&srt¼d&echorr¼true. Accessed August 8, 2007. [48] Kimerling R, Ouimette P, Prins A, et al. Brief report: utility of a short screening scale for DSM-IV PTSD in primary care. J Gen Intern Med 2006;21:65–7. [49] Shalev AY, Friedman MJ, Foa EB, et al. Integration and summary. In: Foa EB, Keane TM, Friedman MJ, editors. Effective treatments for PTSD: practice guidelines from the international society for traumatic stress studies. New York: Guilford Press; 2000. p. 359–79. [50] Butterfield MI, Becker ME. Posttraumatic stress disorder in women: assessment and treatment in primary care. Prim Care 2002;29:151–70. [51] Ursano RJ, Bell C, Eth S, et al. Practice guideline for the treatment of patients with acute stress disorder and posttraumatic stress disorder. Am J Psychiatry 2004;161:3–31. [52] International Psychopharmacology Algorithm Project. Posttraumatic stress disorder algorithm. Available at: www.ipap.org. Accessed March 2, 2007. [53] Stein DJ, van der Kolk BA, Austin C, et al. Efficacy of sertraline in posttraumatic stress disorder secondary to interpersonal trauma or childhood abuse. Ann Clin Psychiatry 2006;18: 243–9. [54] Davidson JR. Long-term treatment and prevention of posttraumatic stress disorder. J Clin Psychiatry 2004;65(Suppl 1):44–8. [55] Vieweg WV, Julius DA, Fernandez A, et al. Posttraumatic stress disorder: clinical features, pathophysiology, and treatment. Am J Med 2006;119:383–90. [56] Krakow B, Hollifield M, Johnston L, et al. Imagery rehearsal therapy for chronic nightmares in sexual assault survivors with posttraumatic stress disorder: a randomized controlled trial. JAMA 2001;286:537–45. [57] Pitman RK, Sanders KM, Zusman RM, et al. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry 2002;51:189–92. [58] Vaiva G, Ducrocq F, Jezequel K, et al. Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Biol Psychiatry 2003;54:947–9. [59] Rothbaum BO, Meadows EA, Resick P, et al. Cognitive behavioral therapy. In: Foa EB, Keane TM, Friedman MJ, editors. Effective treatments for PTSD: practice guidelines from the International Society for Traumatic Stress Studies, vol. 1. New York: Guilford Press; 2004. p. 60–83. [60] Shapiro F. Eye movement densensitization and reprocessing: basic principles, protocols, and procedures. New York: Guilford Press; 1995. [61] EMDR Institute I. A brief description of EMDR. Available at: http://www.emdr.com/ briefdes.htm. Accessed April 13, 2007. [62] Bisson JI, Ehlers A, Matthews R, et al. Psychological treatments for chronic post-traumatic stress disorder: systematic review and meta-analysis. Br J Psychiatry 2007;190:97–104. [63] Bradley R, Greene J, Russ E, et al. A multidimensional meta-analysis of psychotherapy for PTSD. Am J Psychiatry 2005;162:214–27. [64] Figley CR. The family and PTSD. In: Everly G, Lating J, editors. Psychotraumatology: key papers and core concepts. New York: Plenum Press; 1995. p. 341–58. [65] Pfifferling JH, Gilley MS. Overcoming compassion fatigue. Fam Pract Manag 2000;7:39–45.

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Practical Behavior Change Counseling in Primary Care Virginia A. Simons, MSWa,*, Stephen P. Flynn, MD, MSPHa, Susan A. Flocke, PhDb a

Fairview Hospital/Cleveland Clinic Family Medicine Residency Program, Center for Family Medicine, 18200 Lorain Avenue, Cleveland, OH 44111, USA b Department of Family Medicine and Epidemiology & Biostatistics, Case Western Reserve University School of Medicine, 11001 Cedar Avenue, Suite 306, Cleveland, OH 44106, USA

Lifestyle behaviors such as tobacco use, lack of physical activity, poor diet, and excess weight contribute to a large portion of preventable morbidity and mortality in the United States [1]. More than half of all cancers are attributed to these health risk behaviors [2,3]. The US Department of Health and Human Services has designated these lifestyle factors along with substance abuse and responsible sexual behavior as primary indicators of the health of the US population [4,5]. Primary care physicians are well positioned to address unhealthy lifestyle behaviors because the majority of Americans see a primary care physician for multiple visits each year [6]. Thus, primary care physicians have multiple opportunities to tailor advice for behavioral change over time and within the context of an ongoing relationship [7]. Patients also expect their primary care clinicians to be sources of preventive health information and recommendations [8]. In one study, 70% to 80% of primary care visits involved preventive care issues [9]. However, even with recommendations for providing brief advice [10,11], reported rates of diet, physical activity, and smoking counseling are low [12–14]. Encouraging primary care providers to engage in more health behavior counseling requires a working model for understanding and assessing behavior change, brief strategies and tools to use in the clinical setting, and practical methods to address the limitations of time. There are several commonly recommended models for behavior change that may be relevant to the primary care setting [10,15], but the degree to which these models or

* Corresponding author. E-mail address: [email protected] (V.A. Simons). 0095-4543/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pop.2007.05.011 primarycare.theclinics.com

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approaches are fully used is not known. Reports about physician behavior and use of such models often focus on their feasibility and efficacy in a primary care setting in which limited time and lack of reimbursement are significant barriers. There is a gap between recommended use and what occurs in practice [15]. Therefore, the purpose of this article is to describe a practical model for health behavior counseling in a primary care setting. Model for understanding and assessing behavior change Although a number of behavior change models have been proposed, we have elected to use the transtheoretical model (TTM) or stages of change model [16], because it is commonly taught and used in primary care training programs. The TTM was used initially to address alcohol and tobacco use but has since been extended to many other applications, including lifestyle change studies in cancer [17], use with ethnic minorities and diet [18], physical activity interventions [19], and condom use [20]. However, there is some current debate about this model’s reliability in addressing behaviors beyond addictions [21]. Researchers also question the reliability of identification of stages across reporters [22]. Nonetheless, the authors continue to find this model useful in clinical practice because it is easy to understand and use, allows for tailoring interventions, and can be divided into segments to fit shorter time frames. The most effective use of this model is for addressing health behaviors related to primary and secondary prevention in the typical patient. Behavioral change strategies alone cannot address some of the barriers seen in primary care such as psychosocial, psychological, neurobiological, or cognitive impairments. This model may also have limitations when working with more complex biologically and socially reinforced behaviors. In the TTM model, the process of behavior change is conceptualized in five stages: precontemplation, contemplation, preparation, action, and maintenance. In the precontemplative stage, the patient is not even considering a change in a particular behavior or is actively resisting change. In the contemplative stage, a patient is aware of the problem, considering a change, weighing the pros and cons, but not yet committed to making a change. In the preparation/ready stage, the patient is developing plans to make a change in behavior in the near future. In the action stage, patients initiate the behavior change in question. Finally, in the maintenance stage, patients attempt to continue the behavior change and deal with issues of relapse. These stages are fluid, dynamic, and often circular. Patients usually are at different points along this continuum at different times and for different behaviors. Strategies and tools To use this model in the clinical setting, a physician must have a patientcentered perspective along with the skills to assess a patient’s readiness for

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change and to select appropriate treatment strategies to facilitate the patient’s movement through this process. Underlying the entire process of addressing behavioral change is the need for the physician to adopt a patient-centered approach [23]. The patient must do the work of change with facilitation by the provider. This type of counseling may require a conceptual shift that many physicians who are more accustomed to assuming the role of expert advisor may find difficult. This conceptual shift cannot be underestimated and is supported in numerous counseling models where great care is taken to empathize, question, evoke, and collaborate with the client. Motivational interviewing is a patient-centered and empathic interaction designed to explore and reduce inherent ambivalence and resistance in a directive way that encourages self-motivation. Motivational interviewing can be embedded within the TTM and increases the probability of responsible patient behavior. A patient-centered approach has the additional benefit of placing the burden for changing behavior on the patient, where it belongs, and relieves the physician of undue frustration when a patient experiences difficulty in changing behavior. Rollnick and colleagues [24] have provided some practical motivational interviewing tools to assess and work with patients in the precontemplative and contemplative stages of change. This is important because an estimated 60% of the patients seen in primary care settings are in these stages when it comes to changing their health behaviors [25]. Therefore, most of the physician’s time and effort in counseling is spent trying to help patients move from precontemplation and contemplation to the preparation stage and beyond. Rollnick and colleagues [24] describe a method of allowing the patient to decide which of any health behaviors they would be willing to discuss at a particular visit (‘‘setting the agenda’’). It is critical that the patient sets the agenda rather than the physician. Once the patient identifies a health behavior that he is willing to discuss, the physician can then assess the patient’s readiness for change, using general questions or scaling techniques (eg, ‘‘On a scale of 1to 10, how ready are you to change?’’). If the interest in change is very low (precontemplation), the physician can ‘‘raise consciousness’’ by simply expressing concern and the willingness to discuss the issue further at a future visit. She or he may also ask the patient if any specific information is desired or would be helpful. If the patient is willing to enter a further discussion about a particular health behavior, the physician can then ask further questions to understand the patient’s readiness to change. Rollnick and colleagues [24] subdivide the concept of readiness for change into two components: importance and confidence. This is an important distinction from a therapeutic standpoint. For patients who attach little importance to making a change, physicians can use such strategies as having the patient analyze the pros and cons of

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making the change under consideration. This method involves asking patients what they enjoy about the particular behavior under discussion (eg, smoking), what concerns them about the behavior, what would be the benefits of changing the behavior (eg, quitting smoking), and what would be the concerns about making the behavior change. It is important for the patient to do this work with encouragement from the physician. This is an area of temptation for the physician to jump in prematurely to provide answers and suggestions. An additional strategy is using follow-up questions to the patient’s responses on the scaling questions. For example, ‘‘You rated the importance of quitting smoking at 5, that’s good. Why did you rate it 5 rather than 1? Why did you rate it 5 rather than 8? What would it take to get to 8?’’ Finally, the physician can ask the patient what they already know about the risks of the behavior in question and what additional information might be helpful for them to have. Well intentioned but unsolicited information, whether verbal advice or a written pamphlet, will most probably be disregarded. For patients who recognize the importance of making a change but lack the confidence or perceived ability to make the change, different techniques would be appropriate. Scaling questions can be used to assess confidence in the fashion described previously for discussing importance. Exploration of past experiences, especially successes, may remind patients of helpful strategies. ‘‘A look over the fence’’ discussion about how life would be if the change occurred might elucidate new coping mechanisms. Identifying obstacles and ‘‘brainstorming’’ strategies to overcome them may also promote readiness to change. In all cases, the physician needs to let the patient do this work and generate the ideas. Too often, physicians eagerly offer suggestions, only to be met with ‘‘I tried that but it didn’t work.’’ When the patient is in the preparation or action stage, certain other strategies need to be used. It is not clinically relevant to separate these two stages because the interventional techniques are the same. This is where physicians usually are more comfortable in providing advice to patients. The physician’s expertise and knowledge of the issue and available resources are important at this point. For example, tips about low calorie methods of cooking, examples of what other people have found useful when trying to quit smoking, or unique exercises for the elderly may be extremely useful. This is where brief intervention strategies such as the five A’s model promoted by the US Preventive Services Task Force may be the most useful. The physician can assist the patient to set a date for the behavior change, to make a public commitment, to plan environmental changes, to identify support systems and community resources, and to identify potential obstacles and behavioral strategies to deal with them. The key here is to help the patients do the work for themselves. In the maintenance stage, the physician’s role is to reinforce the patient’s positive change and to facilitate further discussion about coping mechanisms and dealing with the possibility of relapse.

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Addressing the time limitations For health behavior counseling to become part of everyday primary care clinical practice, it has to fit into the brief time frame for most patient encounters. The periodic health examination is a natural time to focus on lifestyle behavior issues. Patients often want to discuss any number of specific medical complaints during this type of ‘‘complete physical’’ visit. One suggestion is to catalog the patient’s concerns for discussion at future visits, address any immediate issues, and, with the patient’s consent, spend the time at that visit to focus on the ‘‘bigger picture’’ of prevention to identify issues that might actually lead to significant morbidity or premature mortality (eg, ‘‘I would be happy to discuss all your medical concerns at our regular visits in the future. For this type of ‘health check-up’ visit, I usually like to talk about prevention and things that might disable you and contribute to premature death, things like heart disease and cancer. Is this OK with you?’’). In most cases in primary care practice, however, health behavior counseling is opportunistic and occurs during the routine 10- to 15-minute patient appointment. Examples include talking to a patient with bronchitis about tobacco use, a patient with diabetes about healthy eating and weight loss, and a cardiac patient about physical activity. These interventions often are limited to a few minutes. We contend that a brief assessment of readiness to change can be done with two or three questions and an appropriate intervention made. Just raising the issue, providing requested information, and getting the patient’s reaction may be enough. In those people ready to change, brief advice and resource information may mobilize the patient to action. Time will be saved by avoiding prolonged and circuitous discussions with those not ready to change. The patient can be given some ‘‘homework’’ to do before the next visit. Often, patients have time to think things over in the interval and may come back with more ideas.

Case example Mr. G is 56 years old with a history of diabetes, hypertension, and elevated cholesterol. He is coming in for his usual follow-up appointment with no new complaints. His diabetes is not well controlled. His blood sugar readings at home vary considerably but are generally high. Recently, he lost about 10 pounds, because he ‘‘stopped eating quite as much.’’ Several years ago, he had episodes of chest pain and underwent cardiac catheterization, which showed mild coronary artery disease, which did not require angioplasty. Past medical history The patient had hypertension, diabetes mellitus type 2, and elevated cholesterol levels.

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Medications The patient took insulin glargine once daily; insulin lispro with meals; and pioglitazone, 30 mg daily, for his diabetes. He takes valsartan, hydrochlorothiazide, and atenolol for his hypertension. He currently takes atorvastatin, 20 mg, for his high cholesterol. Social history Mr. G works the night shift as a printer. He has been married for 12 years with two step-children from the wife’s previous marriage. Mr. G. smokes 1 pack of cigarettes per day. His wife is not a smoker and does not allow him to smoke in the house. His wife works full time and has no health risk problems. He drinks alcohol mostly on weekends, reporting an intake of 2 to 4 beers. This is usually with friends over or when he goes out to the bar for the evening. He has no regular physical activity but does have projects he works on around the house such as interior painting, repairing floors, and tile work in the bathrooms or kitchen. He is standing most of the time at his job and does some lifting of boxes. He and his wife have her two children living with them, and he is particularly close to the 14-year-old boy. They work on projects together at home and are working on an old car for the boy to drive once he has a driver’s license. Physical Examination Findings Weight, 250 lbs; body mass index, 35; blood pressure, 160/78 mm Hg Recent Laboratory Values Hg A1C ¼ 9.4% Total cholesterol ¼ 195 mg/dL High-density lipoprotein ¼ 43 mg/dL Low-density lipoprotein ¼ 109 mg/dL Triglycerides ¼ 214 mg/dL The physician has known this patient for 8 years and has taken care of his wife and her two sons also. In past visits, Mr. G has focused more on the medication adjustments that can be made than on changing any of his behaviors. It would be easy to assume he is avoidant of changing behavior and just treat his medical complaints.

Step I: rapport and agenda setting Physician: Hello Mr. G, it is good to see you coming in for your appointment to follow up on your health. Patient: Yes, doctor, I know you gotta keep me going. I’ve got a family to support and the kids are still in high school. Physician: Well, I’ll do my best at my part, and I have to depend on you to not too keep up with the things you can. And you are right, the family needs you healthy. So it looks like you are here for checking up on the

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diabetes and cholesterol. And you also have smoking, diet, and exercise issues going on. Would you say that sums it up? Anything else? (During this exchange, the physician reestablishes rapport with the patient, lets him know it is good that he keeps up with follow-up visits, a point of self-responsibility the physician may want to use for motivation later. The patient expresses a dependency on the doctor to ‘‘fix’’ him, but the doctor gently reminds the patient that he can do so much, and that the partnership between them is a balance of responsibility. Then the physician moves to the agenda of the session, laying out all the issues, including the health behaviors of smoking, diet and exercise.) Patient: That’s about it. So now you’re going to start with telling me to stop something again, right? Stop smoking, or stop drinking, or stop.. something, right? Physician: No, I’m not sure that me telling you to stop something will work in terms of your smoking, weight, and lack of exercise. Would you be interesting in talking about changing any of these, or is there something else more important? (The physician is now letting the patient set the agenda and decide if he wants to talk about any of the health behavior issues. The patient may choose not to address any issue, may choose one that is less important to the physician, or may want to talk about something entirely different. If the patient said he is not interested in any of the health behavior issues (ie, precontemplative), the physician could state his concern and ask the patient if the physician could provide any information, such as educational brochures, referral numbers, or information sheets, that might be helpful.) Patient: There is no way I can stop smoking, and I have already let up on the desserts. I lost ten pounds too, without trying that much really. Physician: I know you have made an effort with the eating and I’m glad you see this as a positive, because it is. Patient: I’m not sure what else I can do. At work, I am standing up a lot and moving some, mainly with lifting. When I get off the night shift, I am tired. Physician: Sounds like you may be questioning if you get enough exercise? Patient: Honestly, I know I’m not, not really. Physician: It sounds like you are considering how you could get more exercise? Do you have any ideas what could work? Patient: I probably could use more, I get no aerobics really. Physician: Just walking and standing is probably tiring but you are right, it is not enough aerobically. Are you interested in talking about how to increase your physical activity? Patient: Yeah, I think I would. That sounds OK. (Now the physician and patient have mutually identified a health behavior to discuss. The physician might have preferred to focus on the smoking behavior but has allowed the patient to set the agenda and thereby increase

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the chance for a productive interaction. This could be a break point, if time is limited. The physician could ask the patient to think of ways that he could add more physical activity and then agree to bring it up again at the next visit. On the other hand, the patient could say he knows he is not getting enough exercise but indicate disinterest in further discussion by being passive. The physician could offer literature on exercise or encouragement to the patient to think about it but end the discussion.) Step 2: assessing readiness for change Applying the transtheoretical model to the conversation above, the physician can infer that the patient is precontemplative about his smoking behavior but at least contemplative about his exercise behavior. Now the physician can further explore the patient’s readiness in terms of the importance attached to the behavior change and his confidence in making the change, either at this visit if time permits or at a future visit. Physician: It sounds like you think that increasing your physical activity is a good idea. On a scale of 1 to 10, with 1 being not important at all and 10 being the most important, where would you rate the importance of increasing your exercise? Patient: I would say 7 or 8. Physician: That’s great. I see that you think this is an important change for you. How confident are you that you can make this change? (The physician has concluded that Mr. G. considers increasing his physical activity important and has moved on to assessing confidence. If the patient had rated the importance lower, then it would have been appropriate to use more clarifying questions about where he rated the importance and also a ‘‘pros and cons’’ analysis. In clinical experience, it is not unusual that patients accept the importance of adding more exercise, so this step often is brief. On the other hand, changing smoking and alcohol behavior is usually rated lower in importance and requires much more discussion, often over a number of visits.) Patient: Well, I am not sure. I work pretty long hours, so I don’t know what I can do. Physician: Has there been a time in the past where you were able to exercise more? What worked for you then? (The physician is assuming by what the patient says that his confidence in making a change is low. It would have been appropriate to ask scaling questions here as well, but not always necessary. The physician can now move into a discussion about past experiences and successes. Brainstorming with the patient may also be a helpful strategy when confidence is low and there is limited experience to draw upon.) Patient: I used to like track and running when I was young. I was never in a gym working out, just always outside. Physician: So you liked the outdoors?

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Patient: Yeah, my wife and I used to take jogs and walks when the kids were little, too. We would take them in the wagon or carrier. Now, she keeps asking me to take the dog out for a walk or run. She does it but doesn’t like to all the time. Physician: Sounds like you enjoyed those times. Do you think walking the dog has possibility? (The physician does not always have time to stay with this discussion long enough for the patient to come up with two or three options in a visit. This is another possible break point. It could have been left for the patient to come up with some ideas before the next visit. It is important not to persist about the things he says will not work for him.) Step 3: preparation/action Patient: I could probably start with walking the dog. I am sure that my wife and dog would like that. Physician: What time of day would work best for you? Patient: Well, I could get up 20 minutes earlier and take the walk before I leave for work. Physician: How many days a week do you think that this would be possible for you? Patient: I could start with three days. For sure, I could walk at least one day on the weekend and try to do 2 during the week. Physician: Do you think that your wife might want to join you? It might be helpful to have an ‘‘exercise buddy.’’ Patient: I could ask her. Physician: Sounds like a good plan to me. When would you want to start your walking program? Patient: I have a lot of things to get to at work this week, so I think that next week would be more realistic. (The patient appears to have moved into the preparation/action stage and is willing to attempt a small change in behavior. As an initial start, this has strong possibilities for the patient to make the change. The physician assisted the patient to address issues about start date, planning his schedule, identifying a possible support person, and committing to a specific plan. One cannot assume the patient will take action, which leads to disappointment and frustration for the physician. Perhaps the goal is too big, or some barrier such as inclement weather occurs. Remembering that change is the patient’s responsibility is key.) Step 4: maintenance Mr. G returned three weeks later for a follow-up visit. He had lost another five pounds, and was tracking his glucose daily. He had started walking the dog and sometimes he and his wife would walk together.

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Physician: How has the exercise been going for you? Patient: Well, I’m not as regular at the exercise as I could be, but my wife loves me more now! (laughs) You know what? We have a pretty smart dog, and now he likes me as much as anyone in that house. I have been taking him to the park and also just on walks. So this dog loves me now, he comes around me all the time. My wife likes this; she used to do all the stuff with the dog. (Smiles) Physician: So your wife loves you more and you’re the dog’s buddy now. Patient: My wife still feeds him but I met some people who walk their dogs too. Mind you, I’m not a social type, but the dogs like each other. I’ve met some nice people. Physician: I am really glad to hear that. About how often are you walking now? Patient: Oh, about three to five times a week. The dog, man, he just loves it and keeps after me ‘til I get up and go. It’s good for me too, and for the dog. Physician: That’s great. It sounds like it is good for everyone. What do you think? Patient: I agree. I wasn’t sure that I could really do it. (It is important that the physician’s encouragement is sincere but also guarded and that the patient ‘‘owns’’ the change. The physician encourages the initial successes, enjoying the step the patient has made toward exercise. He then asks the patient to anticipate possible setbacks or barriers to keeping this step in place. If the patient had come back with no change or discouraged by a more limited success, the physician would repeat previous explorations and find out what barriers the patient experienced. The physician could step back and make sure the steps attempted were not too big or consider if the plan was ill structured in some way.) Physician: Have you anticipated any setbacks or problems keeping this up? What about the winter months? Patient: Well winter is so far off. Maybe by then the walking will become a bit of a habit. Physician: Well think about winter and what you might have to change sometime beforehand. (The physician realizes some behavior changes can have disruptions if the patient does not anticipate and plan ahead.) Step 5: dealing with resistance If the patient had returned without making the behavior change discussed, then the physician can assume that the patient was still in contemplation or encountered some unexpected obstacles to making the change. Sometimes patients will make the change temporarily, only to resume their previous behavior. Changing a behavior often is a cyclical and evolutionary process. The physician can then reassess the patient’s readiness, using the

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various strategies discussed. The physician needs to try to see things from the patient’s perspective and avoid taking a more judgmental or adversarial position. Providing more information upon request may also be helpful.

Future opportunities for changing other behaviors Patients often have multiple behavioral risk factors. In the ongoing relationship of primary care, patients will present opportunities for further behavior change interventions over time. Over the next 12 months, Mr. G was seen twice for routine follow-up visits. He maintained the weight loss and exercise with the dog. In the winter months, he and his wife bought a treadmill and he still took the dog out for short walks. On a later visit, the patient came in for a 3-week history of cough and shortness of breath and was diagnosed with acute bronchitis. The patient expressed some anxiety about smoking and the possibility of lung cancer. This would be a good opportunity for the physician to explore the patient’s readiness to quit smoking, using the model described.

Summary Behavioral change strategies should be fundamental to a primary care physician’s clinical skills. Once mastered, they are easy to integrate into office visits in moments of opportunity. We have attempted to present a practical model for primary care physicians to use when counseling patients about health behavior change. A case example was used to illustrate the application of the transtheoretical model for behavior change with some clinical tools adapted from Rollnick and colleagues [24] and the authors’ clinical experience. The case was based on a typical patient encounter in a primary care practice with multiple unhealthy behaviors. The physician demonstrates staying in the arena that the patient indicates as a possibility for change. This approach alone will certainly not work in all situations. We have indicated its limitations in situations complicated by co-existing medical, psychosocial, cultural, and economic factors that may require other management in addition. Nonetheless, we have found this a useful approach in everyday clinical practice and also as an efficacious model for teaching residents and medical students.

References [1] McGinnis JM, Foege W. Actual causes of death in the United States. JAMA 1993;270: 2207–12. [2] National Cancer Institute, Cancer control objectives for the nation: 1985–2000. National Cancer Institute Monographs 2 (1986). DHHS Pub. No. (NIH)86-2880. 1986, U.S. Department of Health and Human Services: Bethesda (MD).

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[3] Seffrin JR. An endgame for cancer. CA Cancer J Clin 2000;50:4–5. [4] U.S. Department of Health and Human Services, healthy people 2010 (conference edition). January 2000: Washington, DC. [5] Healthy people 2010: understanding and improving health. 2000, U.S. Department of Health and Human Services: Washington, DC: U.S. Government Printing Office. [6] Cherry DK, Burt CW, Woodwell DA. National ambulatory medical care survey: 2001 summaryAdvanced data from vital and health statistics; no 337. Hyattsville (MD): National Center for Health Statistics; 2003. [7] Stange KC, Zyzanski SJ, Jaen CR, et al. Illuminating the ‘black box’. A description of 4454 patient visits to 138 family physicians. J Fam Pract 1998;46(5):377–89. [8] Kottke TE, Edwards BS, Hagen PT. Counseling: implementing our knowledge in a hurried and complex world. Am J Prev Med 1999;17(4):295–8. [9] Binns HJ, Lanier D, Pace WD, et al. Describing primary care encounters: the primary care network survey and the national ambulatory medical care survey. Ann Fam Med 2007;5(1): 39–47. [10] Whitlock EP, Orleans CT, Pender N, et al. Evaluating primary care behavioral counseling interventions: an evidence-based approach. Am J Prev Med 2002;22(4):267–84. [11] U.S. Preventive Services Task Force, guide to clinical preventive services, 3rd edition, periodic updates. May 2004, agency for healthcare research and quality: Rockville (MD). Available at: http://www.ahrq.gov/clinic/uspstmeth.htm. Accessed December 18, 2006. [12] Stange KC, Flocke SA, Goodwin MA, et al. Direct observation of rates of preventive service delivery in community family practice. Prev Med 2000;31:167–76. [13] Makuc DM, Freid VM, Kleinman JC. National trends in the use of preventive health care by women. Am J Public Health 1989;79(1):21–6. [14] Kottke TE, Solberg LI, Brekke ML, et al. Delivery rates for preventive services in 44 Midwestern clinics. Mayo Clin Proc 1997;72(6):515–23. [15] Elder JP, Ayala GX, Harris S. Theories and intervention approaches to health-behavior change in primary care. Am J Prev Med 1999;17(4):275–84. [16] Prochaska J, Norcross JC, DiClementi CC. Changing for good: a revolutionary six-stage program for overcoming bad habits and moving your life positively forward. New York: Harper Collins; 1994. [17] Prochaska J. What causes people to change from unhealthy to health enhancing behavior? In: Cummings C, Floyd J, editors. Human behavior and cancer risk reduction: overview and report of a conference on unmet research needs. Atlanta (GA): Cancer Society; 1989. p. 30–4. [18] Di Noia J, Schinke SP, Prochaska JO, et al. Application of the transtheoretical model to fruit and vegetable consumption among economically disadvantaged African-American adolescents: preliminary findings. Am J Health Promot 2006;20(5):342–8. [19] Marcus BH, Bock BC, Pinto BM, et al. Efficacy of an individualized, motivationally-tailored physical activity intervention. Ann Behav Med 1998;20(3):174–80. [20] Grimley DM, Prochaska JO, Velicer WF, et al. Contraceptive and condom use adoption and maintenance: a stage paradigm approach. Health Educ Q 1995;22(1):20–35. [21] Adams J, White M. Are activity promotion interventions based on the transtheoretical model effective? A critical review. Br J Sports Med 2003;37(2):106–14. [22] West R. Time for a change: putting the transtheoretical (stages of change) model to rest. Addiction 2005;100(8):1036–9. [23] Rollnick S, Miller WR. What is MI? Behavioural and Cognitive Psychotherapy 1995;23: 325–34. [24] Rollnick S, Mason P, Butler C. Health behavior change: a guide for practitioners. New York: Churchill Livingstone; 1999. [25] Prochaska JO, Johnson S, Lee P. The transtheoretical model of behavior change. In: Shumaker SA, Schron EB, Ockene JK, et al, editors. The handbook of health behavior change. New York: Springer Publishing Co.; 1998.

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Personality Disorders Maria Devens, PhD University of Illinois at Chicago, Department of Family Medicine (m/c 663), 1919 W. Taylor Street, Chicago, IL 60612, USA

Personality disorders are starting to gain a similar level of attention in the primary care literature as afforded to mood, anxiety, and substance abuse disorders. The presence of a personality disorderdcomorbid with a medical or other psychiatric diagnosisdpresents a challenge for primary care physicians because of diagnostic and treatment dilemmas, as well as management of the physician’s interpersonal reaction to the patient. In this article, research on prevalence, clinical presentation and assessment, and treatment is reviewed, with specific recommendations for primary care physicians. Strategies to enhance the physician-patient relationship, including the use of empathic skills and the facilitation of physician well-being, are presented. Integrating these tools into routine practice can lead to more satisfying treatment relationships between primary care physicians and patients who have personality disorders. Prevalence/overview The multiple dilemmas with personality or character disorders (herein referred to simply as ‘‘personality disorders’’) in primary care settings are complicated by the fact that all patients have personalities or characters, but not all patients have traits that cause significant difficulties in several spheres of functioning. A recent column in a widely-read medical journal suggests that ‘‘problem’’ patients may in fact be characterized by the diagnosis of personality disorder [1]. Amongst the plethora of medical and mental health issues that primary care physicians encounter on a daily basis, primary care physicians might wonder about the relevance of personality disorder for general medical practice. Put simply, patients who have personality disorders are likely to elicit the attention of primary care providers because of: (1) concerning behavior with regard to use of resources, substance abuse, or illness response; or (2) the interpersonal dynamic between the

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patient and physician. That is, the cue to the presence of a personality disorder will be apparent to the physician over time through indirect but troubling indicators, because patients will not present with ‘‘follow-up for personality disorder’’ as a chief complaint. The underlying goals of this article are to provide an update on literature in this area, in order to increase the primary care physician’s understanding of personality disorder, as well as to provide a therapeutic framework for primary care physicians in their treatment of patients who have personality disorders. The current Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) [2] has maintained the three-cluster system from previous editions. The current system maintains a categorical system, with general criteria for personality disorder and criterion sets for each of the ten specific disorders. The general criteria are: (1) stable and enduring pattern of both inner experience and outward behavior that deviates from an individual’s cultural norms, in at least two areas of functioning (cognition, affect, interpersonal functioning, and impulse control); (2) this pattern of behavior is rigid and transcends personal and social situational parameters, leading to distress or impairment in social, occupational, or other important areas of functioning; and (3) the pattern is stable and chronic in nature [2]. In addition, this pattern of behavior cannot be better accounted for by another psychiatric or general medical disorder, either directly or indirectly, including the physiologic effects of a substance of abuse or medication [2]. The DSM-IV-TR maintains the three-cluster organizational scheme for personality disorders, which remain on Axis II. The disorders in Cluster A are characterized as being ‘‘odd’’ or ‘‘eccentric.’’ Key features of each of the three disorders in Cluster A include: (1) a chronic and pervasive pattern of detachment in interpersonal settings (schizoid); (2) reduced capacity for interpersonal relationships, perceptual distortions, and eccentricities of behavior (schizotypal); and (3) a chronic and pervasive suspiciousness of others, and misinterpretation of their actions as malevolent (paranoid) [2]. The disorders in Cluster B are described as ‘‘dramatic.’’ Key features of each of the three disorders in Cluster B include: (1) chronic instability of interpersonal relationships, sense of self, and mood states, as well as significant impulsivity (borderline); (2) chronic pattern of disregard for others, beginning with conduct disorder symptoms before age 15 (antisocial); (3) grandiosity, need for admiration, and lack of sensitivity toward the feelings of others (narcissistic); and (4) excessive emotionality and seeking of attention, often including inappropriately provocative behavior (histrionic) [2]. The disorders of Cluster C are described as ‘‘anxious.’’ Key features of the disorders in Cluster C include: (1) preoccupation with orderliness, perfectionism, and sense of control (obsessive-compulsive); (2) social inhibition, feelings of inadequacy, and hypersensitivity to negative evaluation (avoidant); and (3) an excessive and all-encompassing need to be taken care of that results in submissive and clinging behavior (dependent) [2].

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In addition to the three disorders included in Axis II, passive-aggressive personality disorder (negativistic personality disorder) is included in the DSM-IV-TR appendix under criteria sets and axes for further study. The diagnosis of ‘‘personality disorder not otherwise specified’’ is used when: (1) general personality disorder criteria are met; however, traits from different personality disorders are present, but criteria for a specific personality disorder are not met; and (2) general personality disorder criteria are met, but criteria for a disorder in the current scheme are not met (such as passive-aggressive personality disorder) [2]. Traditionally the purview of psychiatrists and psychologists, personality disorders have received increasing attention in the general medical literature. Several studies have focused on research in clinical settings. For example, in one large study of 859 psychiatric outpatients, 31.4% met criteria for DSMIV personality disorder [3]. In the general population, prevalence rates for personality disorders have ranged from 10% to 14.3% of the population [4], and borderline personality disorder was equally prevalent in males and females. Previous research has been inconsistent, but borderline personality disorder has been believed to occur more frequently in women than in men. The National Epidemiological Survey of Alcohol and Related Conditions study (NESARC) [5] was the first large-scale, population-based study, involving over 40,000 subjects. The NESARC study assessed prevalence and comorbidity rates for 7 out of 10 of the personality disorders [5]. The NESARC study also contributed to understanding of prevalence rates in the general population. Prevalence rates range from .5% for dependent personality to 7.9% for obsessive-compulsive personality [5]. Somewhat concerning is the 3.6% prevalence rate for antisocial personality disorder in the general population [5]. Future studies will include borderline, schizotypal, and narcissistic disorders [5]. Clinical presentationdor, welcome to the ‘‘Hall of Mirrors’’ Given the prevalence rates of personality disorders within the general population, and increased numbers of individuals who have comorbid mood and substance abuse disorders, it is very likely that most primary care physicians have encountered numerous patients who have personality disorders, with or without a formal psychiatric diagnosis. The most common personality disorder comorbidities include mood, anxiety, substance abuse, and somatization disorders. In primary care practice, patients might report symptoms of the conditions above, or exhibit behaviors associated with one of the above (such as multiple unexplained medical symptoms), or engage in behaviors as the result of substance abuse. General comments on comorbidity The primary care physician may begin to consider presence of personality disorder against the background of an unremitting mood disorder [6].

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Research on the interface of other psychiatric disorders and personality disorders has demonstrated a negative impact of personality disorder on recovery from a comorbid mood disorder [6,7]. Patients who have major depression and concurrent personality disorder typically have more severe depressive symptoms, with longer duration and earlier onset than depressed patients who do not have a personality disorder [6]. Patients diagnosed with borderline personality disorder had an increased co-occurrence of bipolar disorder (19.4%), and patients who had borderline personality disorder were more likely to have a new onset of bipolar I or II disorder [7]. For patients who have known or suspected bipolar disorder, some authors have recommended the importance of assessing personality disorder when the patient does not exhibit significant depressive or manic symptoms (is in the ‘‘euthymic’’ phase). This is useful to minimize misdiagnosis of personality disorder, because of overlap between symptoms of bipolar mood disorder and borderline personality disorder, such as affective instability, impulsivity, and disinhibition [6]. It may be difficult to achieve euthymic status in such patients, however, and primary care physicians may wish to initiate treatment with a provisional diagnosis of personality disorder under consideration. Previous research has demonstrated the comorbidity of Axis I and Axis II disorders [8], in particular anxiety disorders with borderline, avoidant, and dependent personality disorder; psychotic disorders with schizotypal, borderline, and dependent disorders; and eating disorders with schizotypal, borderline, and avoidant disorders. The preceding comorbidity groupings of major Axis I categories with personality disorder argue against associations based upon apparent clinical overlapdsuch as psychotic disorders and personality disorders in Cluster A (schizoid, schizotypal, paranoid), for example. Thus, physicians will need to consider personality disorder diagnoses from all categories when assessing and treating major Axis I disorders. Substance abuse comorbidity The comorbidity between substance abuse and personality disorder has also been demonstrated, with 60% of patients who have substance abuse problem meeting criteria for a personality disorder; and the presence of personality disorder was also associated with a greater level of impairment [9]. Data from the NESARC study discussed above indicate significant comorbidity between substance use disorders and personality disorders [5]. For patients with at least one personality disorder, 16.4% and 6.5% met criteria for a current alcohol use and drug disorder, respectively [5]. Greatest prevalence levels for any alcohol use disorder were obtained for histrionic, antisocial, dependent, and paranoid disorders, with prevalence rates ranging from 19.5% (paranoid) to 29.1% (histrionic) [5]. Levels of comorbid drug use disorder ranged from 12.8% (histrionic) to 18.5% (dependent) [5]. It is striking that alcohol and drug dependence rates are significantly higher among individuals who have specific personality disorders than are

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substance abuse rates. The association between dependent personality and substance use is stronger for men than for women [5]. Somatization disorder comorbidity Patients who have somatization disorder or simply multiple unexplained symptoms represent a source of challenge to the interpersonal resources of physicians and to economic aspect of the health care system. A primary-care based study involving 94 patients diagnosed with somatization disorder demonstrated the high level of comorbidity for these patients [10]. Using structured interviews, 61% of patients who had somatization disorder met criteria for at least one personality disorder, with the most common disorders being avoidant (26.7%), paranoid (21.3), and obsessive-compulsive (17.1%) [10]. Of the patients who met criteria for personality disorder, a substantial portion met criteria for more than one disorder (13.8% for two personality disorders; 23.4% for three personality disorders) [10]. The study authors caution primary care physicians to be more open to the presence of personality pathology in the anxious or odd category, rather than only in the dramatic category (which includes histrionic and borderline disorders) [10]. In addition to patients who have somatization disorder, for patients who have medically unexplained symptoms, the hypothesis of personality disorder might also be warranted [11]. Whereas future research may demonstrate the impact of various personality disorders on use patterns, compliance issues, and health-related quality of life, one can speculate on how personality disorder might impact medical care. For example, the impact of borderline personality traits on the care for patients who have diabetes, from basic medical issues to patient/provider/staff interactions such as glycemic control and treatment noncompliance, have been discussed [12]. Research will also assist in the clarification of the longitudinal clinical course for medical patients who have personality disorders; however, one can speculate that a patient who has avoidant personality disorder might anxiously be in contact with a physician regarding symptom fluctuations and medication side effects. It may be difficult to establish rapport with such patients, who are quite fearful of relationships and are interpersonally sensitive. In contrast, a patient who has paranoid personality disorder might be excessively suspicious of the physician, misread statements that she makes as malicious, and may eventually ‘‘doctor shop.’’ The Rost and colleagues [10] study highlighted the importance of being curious about the patient who has somatization disorder, and not assuming that all patients who have somatization disorder will present in a dramatic fashion. Understanding criterion sets Mnemonics can be helpful in increasing familiarity with criterion sets, and one scheme has been suggested for personality disorders [13]. The

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case below (Cluster A) illustrates an example (name and other identifying data have been changed): Jack is a 19-year-old college student at the university nearby. He presented with complaints of depression. During the visit, Jack expressed his long-standing worry that he was ‘‘losing height.’’ The physician tried to develop some connection with him and found that it was very difficult to do so. The patient avoided eye contact and appeared somewhat odd and disheveled. The physician ended the clinic session feeling unsettled, with the understanding that something was ‘‘not right’’ with this patient after a 20-minute visit. The next day, the physician consulted with the psychologist, who listened to the presentation of the case, considered hypotheses with the physician about possible psychiatric conditions, and offered to see the patient. Subsequently, the patient was seen several times over the course of only a few days in the week after the first appointment, by different providers in the clinic, mainly for ‘‘lost height.’’ All of the providers were mystified by the patient’s complaints, and were unsettled by the patient’s bizarre idea, but were unsure how to proceed. The patient made statements of a paranoid nature, with sexual content, and believed that he was ‘‘sending signals’’ to others. He refused to see a male physician based upon previous experiences. The patient was evaluated by the psychologist, who diagnosed him with schizotypal personality disorderda diagnosis corroborated by the emergency room psychiatrist after the patient decompensated with increasing anxiety and concentration difficulties 1 week after the initial visit. Although the patient described above initially presented with an odd belief, over time, other symptoms became evident. The case above provides an example of the application of the mnemonic for schizotypal personality disorder, outlined in Box 1 below [13]: As the above vignette illustrates, primary care physicians have the opportunity to become acquainted with patients over time, and to observe patterns Box 1. Mnemonic for schizotypal personality disorder: ‘‘MEPECULIAR’’ [13] Magical thinking or odd beliefs Experiences unusual perceptions Paranoid ideation Eccentric behavior or appearance Constricted or inappropriate affect Unusual (odd) thinking and speech Lacks close friends Ideas of reference Anxiety in social situations Rule out psychotic disorders and pervasive developmental disorder

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in behavior that might be consistent with personality disorder diagnoses. When primary care physicians suspect a personality disorder is present, however, it may be more prudent to indicate that the patient exhibits traits of a particular disorder rather than the diagnosis. As discussed in the section on diagnosis, such discriminations are difficult, given the overlap of symptoms in differing disorders. For example, paranoid ideation, magical thinking, and odd beliefs may be found in psychotic disorders as well, but in the latter, such symptoms are persistent and chronic, whereas in schizotypal personality disorder, such symptoms are transient and are often in relationship to stress [2]. Regarding interpersonal communication, individuals who have schizotypal personality disorder have been found to use fewer hand gestures and engage in more self-stimulating behavior (such as playing with shoelaces and hair); higher levels of self-stimulating behavior are associated with fewer gestures, and thus self-stimulating behavior is thought to interfere with nonverbal communication for these individuals [14]. Schizotypal personality disorder has also been associated with greater degrees of movement abnormalities and minor physical abnormalities, when individuals who have this disorder have been compared with those who have other personality disorders or those who do not have a personality disorder diagnosis [15]. Recent research also illuminates the environment in which the patient who has a personality disorder lived and developed as a child. Johnson and colleagues [16] assessed ten types of parenting behavior, and determined that risk for development of personality disorder increased as the number of problem behaviors increased. For example, lower levels of affection and nurturing behaviors were associated with development of antisocial, avoidant, dependent, schizoid, and schizotypal personality disorders. In contrast, aversive parenting practices were associated with an increase in borderline, paranoid, and schizotypal personality disorders [16]. From a developmental perspective, adolescents who have disruptive behavior disorders were more likely to develop Cluster B personality disorders than adolescents who have other emotional disorders [17]. For adolescents who have either disruptive or emotional disorders, females are more likely than males to develop borderline personality disorder, whereas males who have disruptive behavior difficulties are more likely than females to develop antisocial personality disorder [17]. Although physicians cannot base the diagnosis of personality disorder solely on their emotional response to the patient, the patient is likely to manifest certain behaviors in the physician-patient relationship that have caused him difficulty with others. Recall that difficulty in the area of interpersonal functioning is one of the primary symptoms of personality disorder, a feature which transcends ‘‘cluster’’ groupings. Research has supported the stability of personality traits over time, another rationale for developing a consistent ‘‘story’’ for the patient before contemplating a personality disorder diagnosis. If one hypothesizes that a patient might be characterized by a certain personality disorder based on certain traits, over time the physician will have many opportunities to observe and experience the trait in question.

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In one of the first studies to assess the stability of DSM-IV–diagnosed personality traits over time, the Collaborative Longitudinal Personality Disorders Study analyzed borderline, schizotypal, avoidant, and obsessivecompulsive traits over a 2-year period [18]. The most prevalent and least changeable criteria over the 2-year year period were paranoid ideation and unusual experiences (schizotypal personality disorder), affective instability and anger (borderline personality disorder), feeling inadequate and socially inept (avoidant personality disorder), and rigidity and problems delegating (obsessive-compulsive personality disorder). Fortunately, among the most changeable personality disorder traits were self-harming behaviors (borderline personality disorder) [18]. Assessment Unfortunately, there is no ‘‘two-question’’ method for the screening of personality disorders in primary care analogous to screening for depression [19]. Because of comorbidity with substance abuse, mood disorders, and multiple somatic complaints, patients who have personality disorders would benefit from early identification for a number of reasons, including resource utilization [20]. In addition, reasons for early identification include the need to modify treatment expectations, including the adoption of a long-term view of clinical course and outcome, much as one views other disorders with chronic courses, such as hypertension. Early assessment may help to attenuate physician frustration and increase understanding of the patient, and of issues such as nonresponse to treatment or difficulty engaging in otherwise ‘‘straightforward’’ self-management strategies. Patients who have personality disorders make more visits to primary care physicians, but agreement between primary care physician ratings and standardized assessments is poor [21]. Primary care physicians rated patients perceived to be diagnosed with a personality disorder to be less compliant, less likeable, and more stressful to deal with; however, patients who have personality disorder diagnoses obtained from standardized assessment did not elicit negative or adverse perceptions by physicians [21]. Tyrer [20] notes that the poor level of agreement between primary care physician and structured interview assessment may reflect one indicator of personality disorder missed in structured interviews. That is, maladaptive physician-patient interactions may be one manifestation of interpersonal functioning that is not adequately measured by currently available methods. Currently, formal assessment of personality disorder is limited primarily to the use of self-report and semistructured diagnostic evaluations performed either by research personnel or mental health professionals. This assessment approach corresponds to the use in the DSM-IV-TR (and in previous versions of the DSM) of categorical diagnoses [2]. As Westen and colleagues [22] and others have enumerated, the categorical approach is limited in assisting with understanding of matters such as personality health and functioning of individuals who have personality disorder traits,

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but who are subthreshold personality disorder diagnosis. The prototype approach to assessment [22] is being investigated as an alternative approach that might offer more utility in clinical settings, including primary care, though further research is warranted to determine application of the prototype method in primary care settings. Using the prototype approach would involve the physician reading a description of how the personality disorder would be manifested in its ‘‘exemplary’’ or pure form in a paragraph, rather than a list. The paragraph format is more detailed than the criterion lists in the DSM-IV-TR [2] system, and offers a more complex picture of how the individual might present to the physician in a straightforward manner. The physician would then evaluate the patient in terms of similarity to the prototype for a given disorder, with possible ratings ranging from 1, ‘‘little or no match’’ (description does not apply to this patient), to 5, ‘‘very good match’’ (patient exemplifies this disorder, a prototypical case) [22]. Diagnosis may be made based on ratings of 4 or 5, whereas features are present for patients with a rating of 2 or 3 [22]. In this manner, prototype diagnosis offers both categorical and dimensional ratings of personality disorder, and research endeavors to date indicate that the prototype method is promising from the perspective of validity, ease of use, and clinical utility [22]. Based upon clinical experience, this author has found that the first challenge in interactions with patients who have a personality disorder is the establishment of a consistent therapeutic relationship. The direct assessment of personality disorder symptoms through the use of either standard selfreport or semistructured interviews is neither practical nor clinically meaningful for primary care providers; however, the physician can proceed with standard assessment of symptoms presented by the patient or which are the cause of some distressddepression, anxiety, hypomania, functional disturbances, and substance abuse may be clues to an underlying personality disorderdand may be assessed directly. For example, patients who have personality disorder and depression experience more impairment and role limitations caused by emotional problems, suicidal functioning, and general health perception than depressed patients who do not have comorbid personality disorders [23], and the physician may inquire directly about these issues. The physician may consider presence of underlying personality disorder over time, as the physician-patient relationship develops through a number of interactions. Alternatively, a single encounter may serve as the ‘‘stage’’ onto which a patient’s interpersonal dynamics are portrayed, with the physician an unwitting actor, until the intermission arrives and the physician is able to process the encounter. To better determine the presence of personality disorder, the previously referenced mnemonic on schizotypal personality disorder may be applied in addition to the personality disorder criteria. Mnemonics for two other disorders, borderline and dependent, may be particularly useful for primary care providers (Boxes 2 and 3) [13].

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Box 2. Mnemonic for borderline personality disorder: ‘‘AM SUICIDE’’ [13] Abandonment Mood instability (marked reactivity of mood) Suicidal (or self-mutilating) behavior Unstable and intense relationships Impulsivity (in two potentially self-damaging areas) Control of anger Identity disturbance Dissociative (or paranoid) symptoms that are transient and stress-related) Emptiness (chronic feelings of)

Primary care providers must also attend to ‘‘red flags’’ such as suicidal/homicidal ideation and potential for self-harm. As mentioned above, the self-injurious behaviors in borderline personality disorder are among the most changeable [18]. In addition to inquiring directly about behaviors that could involve injury to self or others, inquiry about recent negative life events can alert the primary care provider to have a higher index of suspicion regarding potentially lethal behaviors. In a study with 489 patients diagnosed with personality disorders, 61 made a suicide attempt during a 3-year follow-up period [24]. Negative life events, in particular matters related to love/marriage and crime/legal were significant predictors of suicide after controlling for borderline personality disorder diagnosis, depressive disorder, substance abuse disorder, or history of childhood sexual abuse [24]. The primary care

Box 3. Mnemonic for dependent personality disorder: ‘‘RELIANCE’’ [13] Reassurance required for decisions Expressing disagreement difficult (caused by fear of loss of support or approval); Life responsibilities (needs to have these assumed by others); Initiating projects difficult (caused by lack of self-confidence) Alone (feels helplessness and discomfort when alone) Nurturance (goes to excessive lengths to obtain nurturance and support); Companionship (another relationship) sought urgently when close relationship ends Exaggerated fears of being left to care for self

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provider can develop an understanding of the patient through the use of genograms [25] or the family circle method [26], and both tools have been part of the practice of family medicine for years. The family circle [26] method can be completed by the patient while the provider is in between patients, or as a ‘‘homework’’ assignment, and reviewed at a subsequent visit with the provider. To begin, the physician would draw a large circle which represents ‘‘the family.’’ The patient then is asked to draw smaller circles inside (or outside) the larger circle to represent herself and others in relation to herdthe ‘‘others’’ can be individuals with whom the patient has a positive or negative relationship, or someone from the past who continues to impact the patient in some way, and may not be a biological relative [26]. The patient is then asked to describe her family circle, and is able to disclose such details of her life as are comfortable at the time. The physician may also frame questions regarding family/relationship dynamics and coping strategies across visits [26]. Use of these methods provides insight into cultural factors and family dynamics, which can assist with both establishment of empathy and identification of personality disorder symptoms. Given the literature on the developmental background of patients who have personality disorder (either lower levels of affection or increase in punitive behaviors), an understanding of these relationships can help to identify sources of either support or troubled family relationships [16,23].

Treatment/management Interventions in primary care In addition to application of personality disorder criteria and other adjunctive methods such as the family circle, one clue to presence of a personality disorder might be a complicated clinical course for treatment of a mood disorder or chronic medical condition. Previous research has mainly focused on the impact of personality disorder on the treatment of depressive disorder. In a study of older adults who had depression, presence of a comorbid personality disorder in Cluster C (avoidant, obsessive-compulsive, or dependent) predicted a longer time to treatment response to antidepressant medication and psychotherapy treatment during the acute phase, and nonresponse during the continuation or maintenance phase [27]. As Soloff [28] noted, however, although patients who have comorbid personality disorders have poorer results in research trials when contrasted with patients who do not have comorbid personality disorder, it is unclear whether the personality disorder leads to perception of increased severity of the depressive symptoms, or if an interaction occurs between personality disorder symptoms and biology of depressive symptoms and response to treatment [28]. Regarding the relationship between personality disorders and anxiety disorder, one study demonstrated that the negative impact of personality disorder on the treatment of anxiety is not as strong as for depression [29], but another

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longitudinal, naturalistic study [30] found that patients who had underlying avoidant and dependent personality disorder had lower rate of remission from generalized anxiety disorder, and those who had avoidant personality disorder also had a lower likelihood of remission from social phobia [30]. Implications of the current findings suggest that use of higher doses or waiting more weeks to see therapeutic impact before trying different class of medications may be warranted in the management of patients who have comorbid mood and anxiety disordersdagain, adopting a long-term view toward both assessment and treatment. In the primary care setting, two broad categories of treatment may be offered for personality disorders: pharmacotherapy and counseling. As discussed by Soloff [28], use of medications for personality disorders is aimed at symptoms that require the most attention, and include several categories. The two that have been most researched include the neuroleptics and selective serotonin reuptake inhibitors (SSRIs), but anxiolytics, lithium carbonate, anticonvulsants, and mood stabilizers can also be used [28]. Pharmacologic agents are useful for overall management in patients who have severe personality disorders for symptoms of cognitive disturbance, dysregulation of affect, and impulse control difficulties, but character disorder and interpersonal dynamics are not responsive to medication, and require psychotherapy [28]. A multimodal approach, including psychotherapy and educational interventions, and perhaps involving multiple medications, is recommended [28]. Two counseling techniques that have been developed for use in primary care are the BATHE technique [31] and the five A’s [32,33]. The acronym BATHE stands for items that the physician can inquire about within the context of a 15-minute visit: Background, Affect or feeling state, Trouble (what is most troubling for the patient), How is the patient handling the issue, and Empathy [31]. Beginning with the patient’s presentation, which could include difficulty with an interpersonal relationship, the primary care physician can address aspects of the issue with this technique. The five A’s technique [32,33] has been demonstrated to be effective in counseling for smoking cessation and alcohol abuse in primary care. The five A’s are: Assess, Advise, Agree, Assist, and Arrange follow-up. Given the significant comorbidity between personality disorders and substance abuse, the five A’s model is a practical, evidence-based approach for assisting personality disordered patients with one aspect of life that is causing them distress. Both the BATHE and five A’s models are patient-centered and involve the patient in identifying the specific problem as well as coping strategies or solutions. To use the above techniques, it is essential that the physician take a longterm view toward the relationship with the patient, based on curiosity about the patient as a person, and concern for her well-being. Brief, regularly scheduled visits are required to develop a treatment relationship that is based on positive interactions. By being mindful of specific tools and strategies for both assessment and treatment, the physician can use these

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techniques in response to difficulties in the patient’s life that cause distress or impact treatment course for a medical condition. Referral to mental health colleagues: when and how To illustrate a successful referral process, let us review the case of Jack, described above in the illustration of schizotypal personality disorder. Jack was seen briefly in the emergency room, and was not admitted. After decomensating several weeks later, the patient was subsequently admitted for a 24-hour stay, but refused pharmacotherapy. Upon discharge, he continued to see the psychologist and other family medicine physicians who provided supportive caredthis included information in response to the patient’s presenting complaints (for example, a handout on stretching exercises was provided when the patient complained of multiple mild muscular pains). The patient continued to decompensate, however. Finally, because the patient was frustrated that he was not ‘‘getting better’’ and was continuing to ‘‘shrink,’’ he was amenable to a referral to the department of psychiatry, coordinated by the psychologist. The patient was receptive to the referral at this time, and felt that his concerns had been taken seriously. After referral to psychiatry for multidisciplinary treatment, the patient continued to keep follow-up appointments with providers in the family medicine department, with the primary care treatment relationship maintained. Referral to a specialist should be framed as a consultation to discuss the issues that have not been successfully treated by the primary care physician. In the case discussed above, the patient accepted the referral to psychiatry because of a link that was made between his ‘‘lack of progress’’ with regard to his loss of height and the care that his family medicine physicians and the psychologist had been able to offer. In addition, the patient offered a specific follow-up appointment with his family medicine physician to insure continuity of care for the patient. As in this example, it is important that efforts be made to maintain an ongoing relationship with the patient, and with the patient’s written permission (and the appropriate releases of information in place), to communicate with the mental health specialist for continuity of care. The primary care physician can facilitate a psychotherapy referral for personality disorders, and there is strong research evidence to support this recommendation. In a longitudinal, naturalistic study of combined pharmacotherapy and long-term psychodynamic psychotherapy involving patients who had depression, anxiety, and comorbid personality disorders (the most common disorders were borderline, self-defeating, avoidant, and narcissistic), long-term psychotherapy was associated with improvement in functioning and distress, with and without concurrent medication treatment [34]. In fact, the patients in the psychotherapy-only group demonstrated more significant reductions in levels of depression, relative to those who were taking medications. The authors noted, however, that the patients who had been prescribed medications before entering the study may have demonstrated significant improvement before the study’s initiation [34].

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Kool and colleagues [35] also demonstrated that for depressed patients who had comorbid personality disorder, combined treatment was more effective than medications alone. The most common comorbid personality disorders were paranoid, avoidant, dependent, and borderline; however, Kool and colleagues [35] recommend that psychotherapy focus on all aspects of the patient’s functioning and relationships, rather than solely on symptoms and patient complaints. Finally, dialectical behavior therapy [36] has been demonstrated to be effective in treatment of patients who have borderline personality disorder, and importantly, has been demonstrated to be effective in the reduction of suicidal behaviors [37]. A how-to guide for primary care physicians  Assessment: clinical considerations Significant alcohol and substance abuse Unremitting anxiety or mood disorder, despite use of effective psychotropic medications Somatization disorder or multiple medically unexplained symptoms with functional complications  Assessment tools Family circle method [26] Mnemonics [13] Prototype method [22], if developed in the future  Management Counseling with established models such as the five A’s [32,33] or BATHE [31] Use of psychotropic medications Therapeutic use of ‘‘patient frustration’’ to increase patient acceptance of referral for psychotherapy or psychiatric treatment Special considerations More than with any other treatment population, the importance of having clear boundaries and an established practice protocol cannot be overemphasized when treating patients who have personality disorders. Although most physicians might be apt to consider the importance of such parameters in interactions with patients who have borderline personality disorders, this recommendation is true for others as well. For example, those who have paranoid or schizotypal personality might be prone to perceiving negative messages, whereas those who have dependent or avoidant personality might react with great sensitivity and excessive neediness to the physician’s comments. The physician might consider employing treatment guidelines on a consistent basis, as the treatment relationship is established, rather than trying to implement guidelines in the face of a possible boundary issue with a patientdalso known as ‘‘damage control.’’ If these guidelines are

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reviewed with all patients, such comments can honestly be prefaced with ‘‘This is how my practice functions, so I provide all of my patients with these guidelines.’’ Some points for consideration include the following:  What is your policy with regard to e-mail contact?  Do patients have your pager number or cellular phone number?  Do you have a treatment agreement designating physician and patient responsibilities as outlined above?  Does the agreement outline conditions under which the physician/patient relationship might be terminated, and a plan for follow-up care for the patient (including a 30-day refill of any medications?)  Do all patients in the practice review and sign the agreement, or does it tend to be employed in response to difficulties? Consideration of the above treatment parameters will help to ‘‘anchor’’ the primary care practice, particularly amidst higher levels of patient and provider affectivity that may characterize interactions with personality-disordered patients. The second important strategy involves physician self-care and well-being, increasingly the focus of interventions aimed at reducing burnout. Two activities that relate directly to patient care are consultation with a colleague and Balint groups. Consultation may include discussion with colleagues within one’s practice, as well as with others from psychiatry or psychology. Consultation with a colleague, including a mental health specialist, is recommended when the primary care provider is seeking a second opinion before taking actions that might be different from his usual practice. Consultation may be aimed at answering questions related to the physician’s personal response to a patient and how to manage it, or related to how to interface with the patient to provide effective treatment. If the physician is considering referral to the consultant, he should have expertise in treating patients who have comorbid psychiatric and medical conditions, such as a health psychologist or consultation-liaison psychiatrist. Informal and formal support group meetings where challenging patient encounters can be discussed offer another useful forum for primary care physicians. One format for formal support groups is the Balint group. Whereas general practice physicians in Europe continue to participate in Balint groups, with significant benefits to their professional quality of life [38], in the United States Balint groups are offered in residency programs in family medicine, and increasingly in other primary care disciplines. Balint groups offer physicians the chance to reflect on interactions from the perspective of the physician-patient relationship, with the outcomes being increase in empathy and understanding for both patient and physician; and they also foster the development of the physician’s emotional life. Peer support groups, informal discussions at professional conferences, and even online discussions can offer primary care physicians meaningful and important opportunities for processing and increasing understanding of patients who have personality disorders.

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Pearls/take home messages Historically, patients who have personality disorders have been referred to as ‘‘difficult’’ or ‘‘challenging.’’ Although prevalent in the general population, patients with personality disorders seen in primary care will not volunteer their ‘‘personality’’ as the chief complaint, analogous to requests to follow up on laboratory results or for medication refills. Physicians in primary care need to be mindful of common comorbid conditions and presenting symptom constellations, including mood, anxiety, and substance abuse disorders. With curiosity regarding a comorbid personality disorder, the primary care physician can proceed to use general tools for other psychiatric conditions, as well as those used to gain an understanding of the patient as a person, such as the family circle technique, to develop an increased awareness of the patient’s personality. Regularly-scheduled, time-limited visits will facilitate data gathering and discussion of subsequent treatment options, which include brief counseling, pharmacotherapy, and specialty referrals. Finally, the importance of practice parameters and boundaries, along with Balint groups where available, will help maintain physician well-being. The time has come for primary care physicians to apply their greatest ‘‘intervention’’dthe physician–patient relationshipdto enhance their professional quality of life in treating patients who have personality disorders, and to collaborate with them in the achievement of optimal treatment outcomes. Acknowledgments The author wishes to thank Samuel N. Grief, MD, FCFP, and Marilyn T. Erickson, PhD, for reviewing previous versions of this manuscript. References [1] Lamberg L. Personality disorder a possibility in ‘‘problem’’ patients, specialists say. J Am Med Assoc 2006;296(11):1341–2. [2] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edition, Text Revision. Washington, DC: American Psychiatric Press; 2000. [3] Zimmerman M, Rothschild L, Chelminski I. The prevalence of DSM-IV personality disorders in psychiatric outpatients. Am J Psychiatry 2005;162:1911–8. [4] Torgerson S. Epidemiology. In: Oldham JM, Skodal AE, Bender DS, et al, editors. Textbook of personality disorders. Washington, DC: American Psychiatric Publishing, Inc; 2005. p. 129–41. [5] Grant B, Stinson FS, Dawson DA, et al. Co-occurrence of 12-month alcohol and drug use disorders and personality disorders in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry 2004;61:361–8. [6] Bajaj P, Tyrer P. Managing mood disorders and comorbid personality disorders. Curr Opin Psychiatry 2005;18:27–31. [7] Gunderson JG, Weinberg I, Daversa MT, et al. Descriptive and longitudinal observations on the relationship of borderline personality disorder and bipolar disorder. Am J Psychiatry 2006;163:1173–8.

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[8] Oldham JM, Skodol AE, Kellman HD, et al. Comorbidity of Axis I and Axis II disorders. Am J Psychiatry 1995;152:571–8. [9] Skodol AE, Oldham JM, Gallaher PE. Axis II comorbidity of substance use disorders among patients referred for treatment of personality disorders. Am J Psychiatry 1999;156:733–8. [10] Rost KM, Akins RN, Brown FW, et al. The comorbidity of DSM-III-R personality disorders in somatization disorder. Gen Hosp Psychiatry 1992;14:322–6. [11] Kroenke K, Rosmalen JGM. Symptoms, syndromes, and the value of psychiatric psychiatric diagnostics in patients who have functional somatic disorders. Med Clin North Am 2006;90: 603–26. [12] Leichter SB, Dreelin E. Borderline personality disorder and diabetes: a potentially ominous mix. Clin Diabetes 2005;23:101–3. [13] Pinkofsky HB. Mnemonics for DSM-IV personality disorders. Psychiatr Serv 1997;48: 1197–8. [14] Mittal VA, Tessner KD, McMillan AL, et al. Gesture behavior in unmedicated schizotypal adolescents. J Abnorm Psychol 2006;115:351–8. [15] Mittal VA, Dhruv S, Tessner KD, et al. The relations among putative biorisk markers in schizotypal adolescents: minor physical anomalies, movement abnormalities, and salivary cortisol. Biol Psychiatry 2007;61:1179–86. [16] Johnson JG, Cohen P, Chen H, et al. Parenting behaviors associated with risk for offspring personality disorder during adulthood. Arch Gen Psychiatry 2006;63:579–87. [17] Helgeland MI, Kjelsberg E, Torgersen S. Continuities between emotional and disruptive behavior disorders in adolescence and personality disorders in adulthood. Am J Psychiatry 2005;162:1941–7. [18] McGlashan TH, Grilo CM, Sanslow CA, et al. Two-year prevalence and stability of individual DSM-IV criteria for schizotypal, borderline, avoidant, and obsessive-compulsive personality disorders: toward a hybrid model of Axis II disorders. Am J Psychiatry 2005;162:883–9. [19] Arroll B, Khin N, Kerse N. Screening for depression in primary care with two verbally asked questions: cross sectional study. BMJ 2003;327:1144–6. [20] Tyrer P. Medical settings. In: Oldham JM, Skodol AE, Bender DS, editors. Textbook of personality disorders. Washington, DC: American Psychiatric Publishing, Inc.; 2005. p. 607–19. [21] Moran P, Rendu A, Jenkins R, et al. The impact of personality disorder in UK primary care: a 1-year follow-up of attenders. Psychol Med 2001;31:1447–54. [22] Westen D, Shedler J, Bradley R. A prototype approach to personality disorder diagnosis. Am J Psychiatry 2006;163:846–56. [23] Skodol AE, Grilo CM, Pagano ME, et al. Effects of personality disorders on functioning and well-being in major depressive disorder. J Psychiatr Pract 2005;11:363–8. [24] Yen S, Pagano ME, Shea MT, et al. Recent life events preceding suicide attempts in a personality disorder sample: findings from the Collaborative Longitudinal Personality Disorders Study. J Consult Clin Psychol 2005;73:99–105. [25] Rogers JC, Cohn P. Impact of a screening family genogram on first encounters in primary care. Fam Pract 1987;4:291–301. [26] Thrower SM. The family circle: a transcultural family systems/psychosocial assessment tood for primary care. In: Fisher GC, Lam CLK, Niederstadt CJ, et al, editors. Functional health outcomes in primary care and family medicine: proceedings of a WONCA research group meeting, Projekt Verlag. Hanover (Germany): Hanover Medical School; 1998. p. 175–89. [27] Morse JQ, Pilkonis PA, Houck PR, et al. Impact of Cluster C personality disorders on outcomes of acute and maintenance treatment of late-life depression. Am J Geriatr Psychiatry 2005;13:808–14. [28] Soloff PH. Somatic treatments. In: Oldham JM, Skodal AE, Bender DS, et al, editors. Textbook of personality disorders. Washington DC: American Psychiatric Publishing, Inc; 2005. p. 387–403. [29] Weertman A, Arntz A, Shouten E, et al. Influences of beliefs and personality disorders on treatment outcome in anxiety patients. J Consult Clin Psychol 2005;73:936–44.

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[30] Massion AO, Dyck IR, Shea T, et al. Personality disorders and time to remission in generalized anxiety disorder, social phobia, and panic disorder. Arch Gen Psychiatry 2002;59: 434–40. [31] Stuart MR, Lieberman JA. The fifteen minute hour: applied psychotherapy for the primary care physician. Westport (CT): Praeger; 1993. [32] Whitlock EP, Orleans CT, Pender N, et al. Evaluating primary care behavioral counseling interventions: an evidence-based approach. Am J Prev Med 2004;22:267–84. [33] Whitlock EP, Polen MR, Green CA, et al. Behavioral counseling interventions in primary care to reduce risky/harmful alcohol use by adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2004;140:557–68. [34] Bond M, Perry C. Psychotropic medication use, personality disorder, and improvement in long-term dynamic psychotherapy. J Nerv Mental Dis 2006;194:21–6. [35] Kool S, Dekker J, Duijsens IJ, et al. Efficacy of combined therapy and pharmacotherapy for depressed patients with or without personality disorders. Harv Rev Psychiatry 2003;11: 133–41. [36] Linehan M. Cognitive-behavioral treatment of borderline personality disorder. New York: Guilford Press; 1993. [37] Linehan MM, Comtois KA, Murray AM, et al. Two-year randomized controlled trial and follow-up of dialectical behavior therapy vs. therapy by experts for suicidal behaviors and borderline personality disorder. Arch Gen Psychiatry 2006;63:757–66. [38] Kjeldmand D, Holmstrom I, Rosenqvist U. Balint training makes GPs thrive better in their job. Patient Educ Couns 2004;55:230–5.

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Screening and Responding to Family and Intimate Partner Violence in the Primary Care Setting Sherry A. Falsetti, PhD Department of Family and Community Medicine, Family Medicine Residency Program, University of Illinois College of Medicine at Rockford, Family Health Center, 1221 East State Street Rockford, IL 61104, USA

Family and intimate partner violence (IPV) includes the intentional intimidation, abuse, or neglect of children, adults, or elders by a family member, intimate partner, or caretaker to gain power or control over the victim. This may comprise a pattern of assaultive or coercive behaviors that includes inflicted physical injury, psychological abuse, sexual assault, progressive social isolation, stalking, deprivation, and threats. Children in families with IPV may be neglected; be the direct recipients of physical, sexual, or psychological abuse; or may witness the abuse of another family member. IPV is prevalent and can have devastating psychological, health, and social consequences. The aims of this article are to review prevalence data, review mental and physical health consequences, and discuss screening and interventions appropriate to primary health care settings.

Prevalence IPV may begin in childhood and can extend into old age. Prevalence estimates of IPV against children are approximately 1 million incidents per year in the United States, with approximately 1100 children dying of abuse and neglect each year [1]. IPV is also witnessed frequently by children, as evidenced by estimates that 10 million children annually witness the punching, kicking, and beating of a parent, usually their mother [2]. Children who have experienced physical or sexual abuse or have witnessed interparental violence have a four- to sixfold increase in risk of physical IPV as adults [3]. E-mail address: [email protected] 0095-4543/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pop.2007.05.004 primarycare.theclinics.com

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The lifetime prevalence of IPV for women has been estimated to be from 25% to 54% [4,5]. Differences in prevalence rates may be because of the use of a variety of definitions of intimate partner violence, differences in how IPV is evaluated, and sampling differences [6,7]. Despite the range in prevalence, even conservative estimates indicate that IPV against women is pervasive, with at least one in four experiencing IPV in her lifetime. In the United States alone this translates to 1 to 4 million women who are physically, sexually, or emotionally abused by their intimate partners each year. IPV is also prevalent during pregnancy. A prospective study of 691 pregnant women found that 17% reported physical abuse during pregnancy. Of the women who reported no prior abuse, 8% indicated they had been abused beginning in their second or third trimester [8]. The incidence and continuation of IPV against women have been less well studied. One study of 657 women in rural South Carolina who participated in a primary care screening program found that 13.8% had experienced IPV within the 5 years before the interview [9]. Of the women who were negative at time one, IPV incidence 1 year later was 4.2%. IPV continued over time for 37% of those women. Similarly, a cohort study of 3429 women conducted by telephone survey reported a prevalence of IPV of 7.9% in the last year, 14.7% within the last 5 years, and 44% over a lifetime. The median duration of IPV was 5 years; although for 5% to 12% of women it persisted for greater than 20 years [5]. IPV rates were higher for younger women, women with lower income and less education, single mothers, and those who had been abused as a child. Men, too, are not immune to IPV. The Department of Justice estimates that 7.6% of men have experienced IPV [10]. A population-based study of 7122 men reported a much higher prevalence of 22.9% who had experienced physical, sexual, or psychological IPV during their lifetime [11]. Older adults are also at risk of IPV. Abuse of older adults has been estimated at 551,000 per year with 90% of the cases being perpetrated by a family member, most commonly an adult child or spouse [12]. The prevalence rates of IPV specifically in health care samples are similarly high. One study of 1268 women in 24 emergency departments and primary care clinics reported that 50% to 57% of the women in the study had experienced physical or emotional abuse, and 26% reported sexual abuse in their lifetime. In the last year, 28% reported emotional abuse, 12% physical abuse, 6% severe physical abuse, and 4% sexual abuse [13]. Impact on physical health IPV can have both acute and chronic health effects. The most obvious is physical injury as a result of physical or sexual abuse. Children may present to primary care settings with a variety of physical injuries. Physical abuse may have been aimed directly at the child, or the child may have made attempts to protect a parent who was being abused. The most common

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injuries seen in abused children are soft-tissue injuries, burns, fractures, and head trauma. Children presenting with fractures, evidence of frequent injuries, unusual injures (bites, cigarette burns, rope marks), untreated chronic diseases, genital and perineal trauma, or second- or third-degree burns may have suffered abuse. Physicians should also be aware that in addition to being the direct victim of IPV, witnessing IPV can also physically affect children of every age. Infants and toddlers who have been exposed to IPV show poor weight gain, poor sleeping habits, and irritability [14]. Studies of IPV and pregnancy have found that abuse during pregnancy is associated with impairment in both the mother and child. Preterm birth or injury caused by a blow to the mother’s abdomen as well as harm to both mother and child from the stress of the abuse is not uncommon. Women exposed to IPV have significantly worse health outcomes compared with nonabused women, use the health care system more often, and rate their health problems as being worse more often than women who are not abused [15]. Longer duration of IPV is associated with incrementally worse health [16]. In a study of 3429 women who belonged to an HMO, women with recent physical or sexual IPV were 2.8 times as likely to report fair or poor health compared with women without a history of IPV. Women with IPV exposure were also more likely to use tobacco, be heavy drinkers, and participate in risky behaviors compared with women reporting no IPV [16]. Other studies have also found higher rates of health problems. In a study of 2535 women aged 21 to 55 years who were enrolled in an HMO, it was found that abused women had a 50% to 70% increase in gynecologic, central nervous system, and stress-related problems compared with women who reported no abuse. Specific health problems included headaches, back pain, sexually transmitted diseases, vaginal bleeding, vaginal infections, pelvic pain, painful intercourse, urinary tract infections, appetite loss, abdominal pain, and digestive problems [17]. A study of 1152 women aged 18 to 65 years conducted in family practice clinics investigated the effects of physical abuse and psychological abuse. Like physical abuse, psychological IPV was associated with disability preventing work, chronic pain, migraine and other frequent headaches, stammering, sexually transmitted diseases, chronic pelvic pain, stomach ulcers, spastic colon, and frequent indigestion, diarrhea, or constipation [18]. The costs of IPV to the health care system are enormous. The United States Centers for Disease Control estimates that IPV costs $5.8 billion dollars annually [19]. Most of the costs, around $4.1 billion, are related directly to health care. Studies of HMO enrollees with medical record indicators of IPV have found that medical costs for these women are an average of $1700 higher a year compared with women with no IPV. Costs were attributable to higher rates of hospitalization, higher general clinic use, mental health services, out-of-plan referrals, and other contemporaneous costs [20,21]. Although it is clear that women with a history of abuse may overuse health

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services, health care providers should also be aware that many batterers may attempt to restrict their wives’ and children’s access to health care. Impact on mental health The psychological consequences of IPV are many. Increased rates of depression, posttraumatic stress disorder, other anxiety disorders, somatization, drug and alcohol abuse, chronic mental illness, and suicide attempts have all been documented in survivors of IPV [11,16,22]. Sleeping disorders, eating disorders, and social dysfunction have also been reported [23]. Bonomi and colleagues [16] found, in a study of 3429 women who belonged to an HMO, that women who were physically or sexually abused had a fourfold increase in severe depressive symptoms compared with women with no reports of IPV. Another study that used data from the National Violence Against Women Survey (NVAWS) found higher levels of physical, sexual, and psychological IPV were associated with higher risk of current depressive symptoms compared with women with no IPV [11]. A study conducted in Spain comparing women who had not experienced abuse, women who had been physically and psychologically abused, and women who had been psychologically abused found that the women in the two abuse groups experienced significantly more depressive symptoms and posttraumatic stress disorder compared with nonabused women. The effect sizes were quite large between abused and nonabused women. The percentage of abused women who had experienced suicidal thoughts (58.7% of physically/psychologically abused women; 43.6% of psychologically abused) and suicide attempts (34.7% of physically/psychologically abused women; 12.7% of psychologically abused) were significantly higher than for the nonabused women (suicidal thoughts 7.7%; suicidal attempts 1.9%) [24]. Screening for interpersonal partner violence in health care settings Barriers for victims of IPV Studies of IPV have noted many factors that have discouraged disclosure of IPV by patients. Patients who have experienced IPV have reported that provider time constraints, insensitivity, judgmental attitudes, and ignorance about IPV have all discouraged disclosure [25–28]. Patients may also be embarrassed to disclose or may not have labeled their experiences as abusive. Studies of what women want from health care providers when disclosing abuse have found that when women disclose abuse they want compassion, validation, respect for their timelines, and information about IPV resources [25–28]. Older women may face additional barriers to disclosure. Older women grew up in a time when IPV was not widely recognized, and health care providers had little training in how to respond. One study of older women

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found that of those that had disclosed, half reported very negative and unsupportive responses from their physicians, which decreased the likelihood of further disclosure to other health professionals [29]. Another barrier is that elderly women are more likely to be seen by their health care provider along with their spouses than younger patients so may be unable to have a private conversation in which to disclose abuse. Generational mores of secrecy about IPV may also serve to increase difficulty in disclosing abuse for older women. In addition to barriers of disclosure, there are also barriers to IPV victims to leaving the relationship. Many physicians who do not have experience with IPV victims may feel frustrated that their patients have not left the relationship and may not be aware that the most dangerous time for women is when they leave the relationship. Leaving should not be equated with the ending of violence. Separated women are 25 times more likely to be assaulted by ex-partners [30]. In addition, 24% to 35% of IPV victims experience even more severe violence after leaving [31]. Perhaps a more helpful way to conceptualize ‘‘leaving’’ is to think of it not as a one-time event but as a process that entails a series of decisions and actions and to ask what will assist women in leaving rather than asking why they stay. Asking how to continue providing support after IPV victims have left is an equally important question, because the challenges that women face once they have left the relationships often are not addressed. There are many barriers to change such as finances, education, perceived threats of harm, religious beliefs about divorce, and fears of losing the children. Women who have been victimized generally have low self esteem and may feel hopeless about being able to make it on their own. The abuser may have made threats that he would kill her, their children, or family pets if she were to try to leave. Many of these barriers remain problems or become even more problematic after women have left the relationship. It is critical that physicians understand that IPV victims are managing many factors, which makes it difficult to ‘‘just leave.’’ Ultimately though, many women do leave abusive relationships. A 5-year nationally representative prospective study found that nearly half of women who were in abusive relationships at time one had left that relationship by the time of follow-up 5 years later [32]. Another study found that predictors of leaving included young age, leaving the relationship previously, having an order of protection, and having an abuse-related physician visit [33]. Seeking but not receiving external support was negatively associated with leaving.

Barriers for heath care providers Studies of physicians and nurses have identified additional barriers to identifying and responding to IPV. Studies conducted in the Unites States have reported dismally low screening rates, averaging around 10% or less

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[28,34,35]. Rates of screening increase to 79% for patients presenting with an injury [28]. A Canadian study of 1000 nurses and 1000 physicians, with 931 completed questionnaires, found of 32% of nurses and 42% of physicians reported routinely initiating the topic of IPV in practice [36]. Surprisingly, despite the fact that less than half of the providers screened for IPV, 65% reported patient disclosure of abuse in the last year. Less than 37% of the sample reported any formal training in screening and responding to IPV. Eight constructs were found to affect whether nurses and physicians routinely inquired for IPV. These included preparedness, self-confidence, professional supports, abuse inquiry, practitioner consequences of asking, comfort after disclosure, practitioner lack of control, and practice pressures. Of these, preparedness was the key concept related to whether practitioners inquired about IPV.

Screening recommendations of professional groups Recommendations regarding screening have been made by several groups. Despite recognition of the magnitude of the problem, there has been little research on the effectiveness of screening and intervention to prevent IPV in the primary care setting. This has resulted in many medical groups making recommendations neither for nor against screening because of insufficient information on which to base recommendations. In 2004 the US Preventive Services Task Force (USPSTF) gave a grade I recommendation [37]. Grade I indicates that there was insufficient evidence to recommend for or against routine screening of parents or guardians for the physical abuse or neglect of children, of women for intimate partner violence, or of older adults or their caregivers for elder abuse. The USPSTF reported that they found no direct evidence that screening for family and intimate partner violence leads to decreased disability or premature death. They found no existing studies that determined the accuracy of screening tools for identifying family and IPV among children, women, or older adults in the general population. The USPSTF found fair to good evidence that interventions reduce harm to children when child abuse or neglect has been assessed. They reported finding limited evidence on the effectiveness of interventions in reducing harm to women and no studies that examined the effectiveness of interventions with older adults. The Canadian Task Force on Preventive Health Care (CTFPHC) also made a grade I recommendation regarding universal screening; however, they added that clinicians should be alert to signs and symptoms of potential abuse and may want to ask about exposure to IPV during diagnostic evaluation if these are present [38]. They also reported that there is fair evidence (level 1) to refer women who have spent at least one night in a shelter to a structured program of advocacy services. The CTFPHC also recommended a program of home visitation for children at high risk of maltreatment.

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At least one study by the Centers for Disease Control and Prevention Task Force on Community Preventive Services found such a program to be effective in decreasing maltreatment episodes [19]. The American College of Obstetricians and Gynecologists (ACOG) guidelines [39] on IPV recommend that physicians routinely ask women direct and specific questions about abuse. Similarly, the American Medical Associationrecommends routine screening of IPV and referrals to community-based services [40]. The American Academy of Family Physicians (AAFP) states that family physicians can provide early intervention by routine screening and identification of abuse [41]. The AAFP recommends that family physicians be alert for the presence of family violence in every patient encounter. Recommendations are also made for working with families to prevent abuse by teaching parenting and conflict resolution skills that promote respectful and peaceful relationships. The American Academy of Pediatrics Committee on Child Abuse and Neglect recommends routine screening of all women for abuse at the time of the well-child check and implementation of a protocol that includes a safety plan for the whole family [42]. Approaches to screening If a physician or a medical practice makes a decision to screen for IPV, several decisions must then be made about who to screen, how often to screen, whether to screen in person or use other tools to screen, who should do the screening, and which tools to use. In addition, thought has to be given as to how to best provide a safe, confidential environment, what training to provide staff, and how to create a culture conducive to screening. Several steps can be taken to create a climate for inquiry. These include practice-based efforts such as buttons, posters, tear-off cards, and newsletters. Most communities have a domestic violence advocacy center or shelter that often will readily supply these materials free of charge. Many can also be found online (Box 1). In addition to office-based efforts, community-based efforts such as public service announcements, local newspaper articles and op-eds articles, and participation in community activities can be helpful in promoting a culture conducive to screening. Training of physicians, nurses and staff can be accomplished using a variety of resources. Many community agencies can be an excellent resource. Some domestic violence advocacy organizations may have grants

Box 1. Online resources Family Violence Prevention Fund: www.endabuse.org National Domestic Violence Hotline: 1-800-799-SAFE (7233) National Sexual Violence Resource Center: www.nsvrc.org

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for partnering on training and are eager to provide training to health professionals. Training can also be done as a component of orientation of new staff and health care providers. Ideally, training on screening and responding to IPV would be incorporated routinely in clinical training at the residency level. At the Family Medicine Residency program with the University of Illinois College of Medicine at Rockford, we work very closely with our local IPV community program, Working Against Violent Environments (WAVE). They have grant funding through the Illinois Department of Public Health specifically to provide training on IPV to health care providers. We work with them as a primary partner on this grant, have cosponsored continuing medical education trainings, and have brought in medical advocates to role-play as patients during Objective Standardized Clinical Exams. They also provide training materials and patient resources that we use in our clinic. There are many potential options in primary care settings as to when and who to screen from screening every patient at every visit to screening once when someone comes in as a new patient to the practice. Other options include screening mothers at well-baby-care visits, prenatal visits, pediatric sick visits, routine or problem-directed visits, and gynecological visits. There remains uncertainty as to the optimal mode of screening for IPV. Some studies have suggested that oral assessment is preferable to written questionnaires, whereas other studies have found computer-based interviewing to be optimal [43]. One study found that women preferred computer or written screening to face-to-face screening [44]. Mixed findings may be a result of not only different modalities but of the difference in questions used. Research from the broader trauma field indicates that behaviorally specific questions yield much higher case findings than questions that ask if a patient has experienced abuse. When asking about abuse it is also helpful to preface questions with normalizing statements. This provides both education about abuse and lets the patient know that all patients are screened routinely about the abuse. If abuse is asked about in an initial assessment tool that asks about other health problems, this also sends the message that all patients are asked about violence in the home. Screening tools are presented in Box 2. It is also important to keep in mind when it is inadvisable or potentially dangerous to screen. It is not appropriate to screen if a patient’s partner refuses to leave the room, the provider cannot secure a private place to conduct the screening, there are concerns that screening the patient is unsafe for either the patient or the provider, or the provider is unable to secure an appropriate interpreter. Similarly, when conducting screening, there are also questions and statements that are victim blaming and are NOT appropriate to ask. Examples include questions such as, ‘‘What did you do to make that happen?’’, ‘‘Why don’t you quit putting up with this and leave?,’’ and ‘‘I can’t help you if you don’t leave the relationship now.’’

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Box 2. Examples of screening tools Observation: Observe behavior before and after encounter of any family members presentdpatient, partner, parent, child. Train all staff to be observant of behaviors that might indicate abuse. Examples of Oral Inquiry: First normalize questions, ‘‘Violence in our society is not at all unusual and can take many different forms. It can happen even with people you know such as a partner or other family member. Because of this I ask all of my patients about their experiences.’’ Then ask directly about abuse, ‘‘Has a partner ever hit, kicked, shoved, hurt or frightened you?’’ ‘‘Has your partner ever threatened to hurt you?’’ ‘‘Do conflicts ever make you fearful or turn in to physical fights?’’ ‘‘When I see a patient with an injury such as yours, it is sometimes because someone has hurt her/him. Has someone been hurting you?’’ Structured Questionnaires *Partner Violence Screening [45] Three questions for physical abuse and safety Good psychometric properties when compared with more comprehensive Conflict Tactics Scale [46] (Sensitivity 71.4%; Specificity 84.4%) *Women Abuse Screening Tool [47] Eight items assessing physical, sexual, and emotional abuseSensitivity 47%; Specificity 95.6% compared with the 30-item Composite Abuse Scale [48] * These scales are also reproduced in MacMillan HL, Wathen CN, Jamieson E, et al. Approaches to screening for intimate partner violence in health care settings. JAMA 2006;296:530–6.

Interventions for interpersonal violence As discussed previously, although only roughly a third of health practitioners are trained to ask about abuse, 65% of them have had disclosures of abuse in the last year [49]. Clearly, regardless of whether health care providers routinely screen for IPV, patients may disclose abuse, and providers need to know how to respond appropriately. In addition, the recognition of abuse may affect the evaluation of a patient’s complaints as well as the outcome of care. Screening and responding to abuse may also help the patient make the connection between the violence and her current symptoms as well as enhance the doctor–patient relationship. It should be kept in mind that intervention most often takes place over several visits. Experts generally agree that intervention for IPV includes the

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following steps: risk assessment, validation and empathy, education about IPV, information about resources and options, safety planning, documentation, and follow-up. Examples of these are presented in Box 3. Studies of women’s perceptions of appropriate immediate and longerterm responses can also be used to inform effective responses to disclosures of abuse and should be considered as interventions are implemented. A meta-analysis by Feder and colleagues [50], of 25 studies examined how women with histories of IPV perceive the responses of health care professionals and how these women want their health care providers to respond. Feder and colleagues [50], identified 14 constructs related to three different areas; desired characteristics of health care professionals, the nature of the consultation with health care professionals, and women’s expressions of their needs. A summary of these constructs is presented in Box 4. How women want health care providers to respond to IPV may also depend, in part, on where they are in terms of the stages of change. The stages of change model typically matches modifications in attitude and behavior with tools that may be cognitive-affective or behavioral activities. One study of medical management of IPV investigated the stages of change represented by victims’ thoughts and behaviors and related that to victims’ opinions of the care they received or wished they received from physicians [47]. Most participants in this study were in the precontemplation and contemplation stages of change. Victims who were in the precontemplation stage did not recognize their partner’s behavior as abusive and viewed their relationships as normal. Most of the women reported, however, that they appreciated the screening or wished they had been screened. Most felt that the screening would have increased their awareness and perhaps sped up the process for them. Women in the contemplation stage viewed the abuse as problematic and had an increasing awareness of the advantages and disadvantages of change. Women may stay in this stage for years. Women in this stage were found to be in one of two phases: nondisclosure or disclosure. Women in nondisclosure recognized the abuse but were either unable or unwilling to disclose. Women in this phase felt that the physician should provide a safe environment and screen for abuse. Women in the disclosure phase had clear expectations about how physicians should react to what they learned. This study identified four expectations including affirmation that the abuse is real, expectations of the physician to know and inform them of local IPV resources, education about the effects of the abuse on their children, and documentation of injuries on the medical record. Physician interventions that were recommended for the precontemplation and contemplation stages were: (1) ask about IPV; (2) share observations about the relationship; (3) educate about the impact of stress/injuries on health; (4) empathize; (5) identify emotional state; and (6) clarify values, experiences, and feelings. There are many factors to consider when responding to IPV. Ultimately, using the tools discussed in a patient-centered manner will likely prove most effective. An example of an actual encounter is given in Box 5.

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Box 3. Intervention components Assessment of risk factors for serious or lethal injury Increase in frequency or severity of abuse Threats of homicide or suicide by partner Abuser knowledge of victim’s plans to leave Frequency and severity of violence Alcohol and drug use Threats to harm children Forced sex Weapons in the home If living apart, also consider in lethality assessment Proximity Need for contact because of children Current stressors in both partner’s lives Abuser’s past criminal history Abuser’s attitude toward violence Presence of new relationships for either partner Provide validation and empathy I believe what you are telling me. You are not crazy. The abuse is not your fault. No one deserves to be abused. I am concerned for your safety. Education about IPV IPV is common. IPV can include not only physical violence, but also emotional abuse. The cycle of abuse can include tension building, abuse, and a honeymoon period. IPV often increases in frequency and severity. Children can be affected by witnessing abuse or being physically hurt. Information about resources and options Advocacy and shelter services Legal services Services for children Counseling services Hotline or support group

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Safety Planning Safety during a violent incidentdStay out of rooms with weapons and sharp objects (ie, bathrooms and kitchens). Safety when preparing to leavedHave an emergency bag with important papers, change of clothes, and car key hidden. Safety in new residencedKeep new address and phone number private. Safety with a protective order Safety in the job and in public Documentation Written descriptions Photographs of injuries Diagrams or sketches indicating location of injuries Follow-up Provide further support. Continue to assess safety. Repeat previous steps as necessary.

Box 4. Desired responses of health care professionals Keep a nonjudgmental attitude. Use compassionate and sensitive inquiry. Provide reassurances of and maintain confidentiality and privacy. Demonstrate an understanding of the complexity of IPV. Understand the long-term nature of IPV. Understand difficulty of a quick resolution. Understand social and psychological consequences of IPV. Avoid ‘‘medicalizing’’ the issue. Raise the issue in a sensitive and confident manner. Do not rush the discussion. Confirm abusive experiences as unacceptable and undeserved. Challenge false assumptions such as ‘‘the abuse is my fault.’’ Build up self-confidence. Respect progressing at their own pace and do not pressure to disclose, leave the relationship, or press charges against the abuser. Respect their decisions and share decision making with them. Allow expression of needs including feelings about the abuse such as shame, embarrassment, fear, humiliation, and denial. Validate experiences and feelings.

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Box 5. Patient encounter example New Patient in Precontemplation with Chief Complaint of Frequent Headaches Physician: ‘‘Violence in our society is not at all unusual and can take many different forms. It can happen even with people you know such as a partner or other family member. Because of this I ask all of my patients about their experiences. Has a partner ever hit, kicked, shoved, hurt, or frightened you?’’ Patient: Well, my husband can get really angry sometimes, but I don’t think he means to hurt me. It’s probably not different than any other marriage. He told me never to tell anyone. He can’t see my medical record, can he? Physician: Your husband cannot see your medical record. Whatever you tell me today will be confidential. The only exception to that would be if you told me that your children were being abused, then I would have to report that the Division of Social Services. Would you like to talk more about what’s happening at home with your husband? Patient: I’m not sure. I’ll have to think about that. Can you give me something for these headaches I’ve been having? Physician: I understand if you need more time to decide if you would like to talk more about what is going on at home. I just want to let you know that you do not deserve to be hurt and that I am here for you. You are safe here to talk about it if you’d like. I can also connect you with resources in our community. Patient: Thank you. That really means a lot to me. Physician: Let’s talk about your headaches. Sometimes headaches can be caused by stress. Do you think what is going on at home may have something to do with those headaches? Patient: I never really thought about it, but I guess so. Things have been getting a lot worse lately. Physician: When you say a lot worse, I’m not sure what you mean. Can you tell me more about that? Patient: Well, he just seems angrier. It’s like I can’t do anything to please him. I feel like I’m walking on eggshells. The other day he threw me against the wall, just because he found some dirt on the floor. Physician: That sounds really frightening. I’m worried for your safety. Patient: Well, afterwards he did apologize. He said it was an accident. He didn’t really mean it.

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Physician: So, you’re really hoping he means it, that he won’t hurt you again. Patient: Yeah, but he’s said that before. Physician: I think it might be really helpful for you to be able to get some support. I know an agency in town that specializes in helping women who are being hurt in relationships. Let me get one of their cards for you. I’d also like to talk with you about how you think you can best stay safe. Are there any weapons in your home? Patient: No we don’t have any guns or anything. He usually just pushes me around. Physician: If you see things are escalating, it can be helpful to stay out of certain rooms in the house, like the bathroom which has a lot of hard surfaces and the kitchen which has knives. It can also be helpful to have a plan to be able to leave the house if you need to stay safe. Having a car key hidden along with some clothes and important papers might help you. Patient: Those are good ideas. I think I can do that. (After physical examination and further review of headaches) Physician: I’d like to see you back in 2 weeks to see how you are doing. Here is the card for the agency I told you about. Please give them a call. Other patients of mine have found them to be very helpful. We can see how those headaches are doing and how things are going at home when you come back in.

Summary IPV is prevalent in our society and is likely to be encountered on a daily basis in primary care settings, regardless of whether the health care provider is aware of it. Screening for IPV remains controversial because of lack of evidence of its effect on reducing morbidity and mortality. Although there may not be strong empirical evidence at this point to support routine screening, one must not forget that there is strong evidence for the negative health effects of IPV. Without knowing the effect of IPV in health problems, the health care provider cannot provide effective treatment, and the patient is likely to overuse services because they are not improving. For this reason, as well as many others, most professional groups do recommend routine screening. Moreover, regardless of whether routine screening is used, patients may disclose IPV, albeit at lower rates, but health care providers must know how to respond effectively. Many intervention strategies as well as victims’ concerns about what they would like from intervention have been reviewed here. Ultimately, more research is needed to determine which screening and intervention practices are most efficacious. As

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Thompson and Krugman [43] in 2001 so compellingly stated, ‘‘The time to act is now. If intimate partner abuse were a new cancer affecting one quarter of adults, the money would be found. It should be found now for family violence’’ [41]. References [1] Child Maltreatment 1999: Reports from the States to the National Child Abuse and Neglect Data System. Washington, DC: U.S. Department of Health and Human Services; 2001. [2] Humphreys J. Nursing care of children of battered women. Pediatr Nurs 1997;23:122–8. [3] Bensley L, Eenwyk JV, Simmons KW. Childhood family violence history and women’s risk for intimate partner violence and poor health. Am J Prev Med 2003;25:38–44. [4] McCauley J, Kern DE, Kolodner K, et al. The ‘‘battering syndrome’’: prevalence and clinical characteristics of domestic violence in primary care internal medicine practices. Ann Intern Med 1995;123:737–46. [5] Thompson RS, Bonomi AE, Anderson M, et al. Intimate partner violence: prevalence, types, and chronicity in adult women. Am J Prev Med 2006;30:447–57. [6] Hegarty K, Roberts G. How common is domestic violence against women? The definition of partner abuse in prevalence studies. Aust N Z J Public Health 1998;20:49–54. [7] Snow Jones A, Carlson GA, Campbell JC, et al. Annual and lifetime prevalence of partner abuse in a sample of female HMO enrollees. Women’s Health Issues 1999;9:295–305. [8] McFarlane J. Abuse during pregnancy: the horror and the hope. AWHONNS Clin Issues Perinat Womens Health Nurs 1993;4:350–62. [9] Coker AL, Flerx VC, Smith PH, et al. Intimate partner violence incidence and continuation in a primary care screening program. American J Epidemiol 2007;165:1–7. [10] Catalano SM. Criminal victimization. Washington, DC: Bureau of Statistics; 2005. [11] Coker AL, Davis KE, Arias I, et al. Physical and mental health effects of intimate partner violence for men and women. Am J Prev Med 2002;23:260–88. [12] The National Elder Abuse Incidence Study (NEAIS). Final report. The National Center of Elder Abuse at the American Public Human Services Association in Collaboration with Westat, Inc. for the Administration for Children and Families and the Administration of Health and Human Services. Washington, DC: American Public Health Services Assoc; 1998. [13] Kramer A, Lorenzon D, Mueller G. Prevalence of intimate partner violence and health implications for women using emergency room departments and primary care clinics. Women’s Health Issues 2004;14:19–29. [14] Jaffee PG, Wolfe DA, Wilson SK. Children of battered women. Newbury Park (CA): Sage; 1990. [15] Koss MP. The negative impact of crime victimization on women’s health and medical use. In: AJ Dan, ed. Reframing women’s health: multidisciplinary research and practice. Thousand Oaks (CA): Sage; 1994. p. 189–200. [16] Bonomi AE, Thompson RS, Anderson M, et al. Intimate partner violence and women’s physical, mental and social functioning. Am J Prev Med 2006;30:458–66. [17] Campbell J, Snow Jones A, Dienemann J, et al. Intimate partner violence and physical health consequences. Arch Intern Med 2002;162:1157–63. [18] Coker AL, Smith PH, Bethea L, et al. Physical health consequences of physical and psychological intimate partner violence. Arch Fam Med 2000;9:451–7. [19] National Center for Injury Prevention and Control. Costs of intimate partner violence against women in the United States. Atlanta (GA): Centers for Disease Control and Prevention; 2003. [20] Jones AS, Dienemann J, Schollenberger J, et al. Long-term costs of intimate partner violence in a sample of female HMO enrollees. Women’s Health Issues 2006;16:252–61.

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[21] Wisner C, Gilmer T, Saltzman L, et al. Do victims cost health plans more? Journal of Family Practice 1999;48:439–43. [22] McCauley J, Kern DE, Kolodner K, et al. Clinical characteristics of women with a history of childhood abuse: unhealed wounds. JAMA 1997;277:1362–8. [23] Golding JM. Intimate partner violence as a risk factor for mental disorders: a meta-analysis. J Fam Violence 1999;14:99–106. [24] Pico-Alfonso MA, Garcia-Linares MI, Celda-Navarro N, et al. The impact of physical, psychological, and sexual intimate male partner violence on women’s mental health: depressive symptoms, posttraumatic stress disorder, state anxiety and suicide. J Women’s Health 2006; 15:599–611. [25] Gerbert B, Bronstone A, Pantilat S, et al. When asked: patients tell. Disclosure of sensitive health-risk behaviors. Med Care 1999;37:104–11. [26] Hathaway J, Willis G, Zimmer B. Listening to survivor’s voices: addressing partner abuse in the health care setting. Violence Against Women 2002;8:687–99. [27] McCauley J, Yurk R, Jenckes M, et al. Inside ‘‘Pandora’s box’’: abused women’s experiences with clinicians and health services. J Gen Intern Med 1998;13:549–55. [28] Rodriguez M, Bauer H, McLoughlin E, et al. Screening and intervention for intimate partner abuse: practice and attitudes of primary care physicians. JAMA 1999;282:468–74. [29] Zink T, Jacobson CJ, Regan S, et al. Hidden victims: the healthcare needs and experiences of older women in abusive relationships. J Women’s Health 2004;13:898–906. [30] Bachman R, Saltzman L. Violence against women: Estimates from the redesigned survey. Washington, DC: U.S. Department of Justice; 1995. [31] Canadian Centre for Justice Statistics. Family violence in Canada: a statistical profile. Ottawa (ON): Statistics Canada; 2000. [32] Zlotnick C, Johnson DM, Kohn R. Intimate partner violence and long-term psychosocial functioning in a national sample of American women. J Interpers Violence 2006;21: 262–75. [33] Koepsell JK, Kernic MA, Holt VL. Factors that influence battered women to leave their abusive relationships. Violence Vict 2006;21:131–47. [34] Institute of Medicine. Confronting chronic neglect: the education and training of health professionals on family violence. Washington, DC: National Academy Press; 2002. [35] Elliot L, Nerney M, Jones T, et al. Barriers to screening for domestic violence. J Gen Intern Med 2002;17:112–6. [36] Gutmanis I, Beynon C, Tutty L, et al. Factors influencing identification of and response to intimate partner violence: a survey of physicians and nurses. BMC Public Health 2007;7: 12–23. [37] U.S. Preventive Services Task Force. Screening for family and intimate partner violence: recommendation statement. Ann Intern Med 2004;140:382–6. [38] Watehn CN, MacMillan HL. Prevention of violence against women: recommendation statement from the Canadian Task Force on Preventative Health Care. CMAJ 2003;169:582–4. [39] American College of Obstetricians and Gynecologists. ACOG issues technical bulletin on domestic violence. Am Fam Physician 1995;52:2387–8, 2391. [40] American Medical Association. Council on scientific affairs. Violence against women: relevance for medical practitioners. JAMA 1992;267:3184–9. [41] American Academy of Family Practice. Family violence. Am Fam Physician 1994;50: 1636–46. [42] American Academy of Pediatrics, Committee on Child Abuse and Neglect. The role of the pediatrician in recognizing and intervening on behalf of abused women. Pediatrics 1998; 101:1091–2. [43] Thompson RS, Krugman R. Screening mothers for intimate partner abuse at well-baby care visits. The right thing to do. JAMA 2001;285(12):1628–30. [44] MacMillan HL, Wathen CN, Jamieson E, et al. Approaches to screening for intimate partner violence in health care settings. JAMA 2006;296(5):530–6.

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[45] Feldhaus KM, Koziol-McLain J, Amsbury HL, et al. Accuracy of 3 brief screening questions for detecting partner violence in the emergency department. JAMA 1997;277:1357–61. [46] Straus MA. Measuring intrafamily conflict and violence: conflict tactic scale. Journal of Marriage and Family 1979;45:75–88. [47] Brown JB, Lent B, Schmidt G. Application of the Woman Abuse Screening Tool (WAST) and the WAST-Short Form in the family practice setting. J Fam Pract 2000;49:896–903. [48] Hegarty K, Bush R, Sheehan M. The composite abuse scale: further development and assessment of reliability and validity of a multidimensional partner abuse measure in clinical settings. Violence Vict 2005;20:529–47. [49] Zink T, Elder N, Jacobson J, et al. Medical management of intimate partner violence considering the stages of change: precontemplation and contemplation. Ann Fam Med 2004;2:231–9. [50] Feder GS, Hutson M, Ramsay J, et al. Women exposed to intimate partner violence: expectations and experiences when they encounter health care professionals a meta-analysis of qualitative studies. Arch Intern Med 2006;166:22–37.

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Insomnia: An Ignored Health Problem Joan E. Hamblin, MD Department of Family Medicine, University of Wisconsin School of Medicine and Public Health, Eau Claire Family Medicine Residency Program, 617 West Clairemont Avenue, Eau Claire WI 54701, USA

‘‘The worst things: to be in bed and sleep not, to want for one who comes not, to try to please and please not.’’ dEgyptian proverb

Insomnia is a common problem affecting persons in all stages of life. According to the National Sleep Foundation 2005 ‘‘Sleep in America’’ Poll, one out of every three respondents reported insomnia symptoms almost every night of the week. Prevalence varies between 20% and 40% of adults in the US having insomnia, and 10% to 15% of adults having chronic insomnia [1,2]. Sleep problems are more prevalent in the elderly; more than 60% of patients over 60 years report sleep difficulties [3]. Children and adolescents are not immune from sleep problems; one out of four children receiving medical care for both acute or chronic medical conditions reported sleep disturbances [4]. Some studies find more than 10% of teenagers struggle with insomnia [5]. In spite of the high prevalence of insomnia, most people who have sleep problems are not diagnosed. Almost 70% of persons who have insomnia never discuss sleep with their doctor, 26% discuss sleep issues during office visits for other problems, and only 5% of persons who have sleep issues schedule appointments with their doctor to discuss their insomnia. Even fewer receive adequate treatment [6]. Definition Insomnia is defined as difficulty falling asleep or staying asleep, or nonrefreshing sleep, for a patient who has the opportunity to acquire a normal night’s sleep of 7 to 8 hours. Insomnia has been classified either based on its specific symptoms (ie, sleep onset or sleep maintenance) or the duration of the disorder. Acute insomnia generally occurs for less than 4 weeks, whereas chronic insomnia occurs for greater than 4 weeks. Some make a distinction E-mail address: [email protected] 0095-4543/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pop.2007.05.009 primarycare.theclinics.com

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of clinically relevant insomnia occurring in conjunction with daytime dysfunction or distress of fatigue, poor concentration, or irritability [7]. Beyond the loss of sleep for the insomniac, insomnia affects the parents of children and infants and caregivers of elderly. Employers of those who have insomnia suffer when the insomniac’s work performance is affected and daytime drowsiness leads to dangerous work behaviors or driving [8]. Transient or acute insomnia is most often caused by a change of sleeping environments; for example, sleeping in a hotel, sharing your bed with a sick child, or sleeping in the summer heat without air conditioning. Jet lag, changes in work shift, excessive noise, unpleasant room temperature, stressful life events, acute medical or surgical illness (including intensive care unit syndrome), and stimulants can also produce short-term sleep disruption. Jet lag occurs after traveling across several time zones. Some of the sleep problems are related to ‘‘jet factor,’’ including long periods of time with limited mobility, dry eyes, headache, fatigue and nasal congestion; whereas ‘‘lag factor’’ results in dyssynchrony between the body’s internal clock and the sleep schedule of the new environment. Symptoms are more severe when traveling from west to east, and are more severe in the elderly. Readjustment and resynchronization occur about 1 hour per day when traveling eastward and 1.5 hours per day while traveling westward, because it is easier to lengthen rather than shorten the natural circadian cycle [9]. Insomnia occurs alone, or with another medical or psychiatric condition, or when the patient develops a conditioned state of hyper arousal or heightened concern that she won’t be able to fall asleep, called ‘‘conditional insomnia’’ [7]. Primary insomnia or sleep disorder occurs without a coexisting disorder. Examples of primary sleep disorders are obstructive sleep apnea, restless legs syndrome, or periodic limp movement disorder. Comorbid insomnia, previously called secondary insomnia, occurs with an underlying medical psychiatric or psychological process. Previously the underlying condition was thought to cause the insomnia, but newer studies [10–12] of the relationships between insomnia and associated medical and psychiatric conditions undermine this notion. Although identifying and treating the underlying condition is important, it may not be sufficient to alleviate the insomnia [13–15]. When insomnia continues, treatment targeted specifically to the insomnia should be considered. Moreover, untreated insomnia may adversely affect the course of the associated disorder. Conditioned insomnia, also known as psychophysiologic insomnia, is a disorder in which the patient typically suffers acute insomnia caused by stress (loss of a loved one, work or marital stress). After several nights of poor sleep and tiredness during the day, the patient becomes anxious about his ability to sleep and perform when tired. This anxiety becomes an exacerbating factor interfering with sleep, and begins a vicious cycle that continues even after the initial stress has resolved. Although affected individuals are overconcerned and overfocused on the problem of sleep, they do not suffer from generalized anxiety, phobic, or other psychiatric

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disorders [16]. The characteristic feature of psychophysiologic insomnia is the development of conditioned responses that are incompatible with sleep. Sufferers make up 15% of all insomniacs attending sleep disorder centers [16]. Natural history Little is known about the duration of chronic insomnia. The limited prospective data suggest that for the majority of insomniacs, symptoms are of long duration, and for some, they are lifelong [13]. Very little is also known about the incidence, or the number of new cases arising each year. Risk factors Although risk factors have been identified, the causal relationships are not fully understood. Known associations for insomnia include older age [17–19], female gender [5,20], present or past psychiatric illness and psychological problems [19–21], multiple medical conditions [15,22], poor general health [22,23], increased health care use [22,23], lower quality of life and social relationships [24], socioeconomic status (marital separation, unemployment, poorer working conditions, and lower social status) [24], and memory and cognitive deficits [25–27]. Although sleep patterns change with age, the ability to sleep is not affected by age alone. The higher rate of insomnia in the older population is probably caused by multiple medical problems, polypharmacy, and environmental factors such as institutionalization and the absence of time and schedule cues, because healthy, active older adults with good social life satisfaction do not seem to have higher rates of insomnia [28–31]. The increased rate for females begins with menarche. Insomnia rates are the same for boys and girls until a girl’s menses, when her insomnia risk increases 2.75 times and continues throughout adult life [5]. Hormones [32], pregnancy [33], menopause, stress, medical conditions, and complex home life [34] may explain the higher prevalence of insomnia in women. The prevalence of chronic insomnia increases with severity of hot flashes; 80% of woman suffering with severe hot flashes report insomnia [35]. There is a strong association between insomnia and psychiatric and psychological disorders: mood disorders (major depression and bipolar), anxiety disorders (generalized anxiety disorder, panic disorder, post-traumatic stress disorder, adjustment disorders), psychotic disorders, and substance abuse [13]. Schizophrenia-associated sleep disturbances are related to the intensity of psychotic symptoms, with extremely prolonged sleep onset latency during acute illness and decrease in total sleep time [36]. Multiple medical conditions have increased rates of insomnia, including pulmonary and gastrointestinal disorders [22], heart disease [15], allergies, arthritis [15], malignancy, neurological diseases (Parkinson’s and stroke)

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[22], hypertension [15], diabetes mellitus [15], and HIV infection [37]. Medical conditions disrupt sleep through a variety of mechanisms: joint or back pain requiring change of position, heartburn in supine position, need to void because of enlarged prostate or polyuria associated with poorly controlled diabetes mellitus, mobilization of fluids with volume overload conditions such as heart failure or venous stasis changes with sleep, shortness of breath when lying flat in congestive heart failure or lung disease, or drugs such as antidepressants and diuretics that interfere with sleep. Insomnia rates increase with the number of medical conditions. In patients who have four or more medical conditions, the insomnia rate reaches 70% [22]. Treating the underlying diseases may not improve the insomnia [15,22,23]. Poor sleep can also aggravate medical conditions [10,38]. There is increasing evidence that chronic insomnia may predispose individuals to the development of psychiatric and medical disorders. One large study [12] found that individuals who had insomnia at baseline were 34 times more likely to develop a new psychiatric disorder (usually major depression) within 1 year compared with those who had no insomnia. The bidirectional relationship between insomnia and mood disorder is complicated and poorly understood. Depression may lead to insomnia, and insomnia increases the risk of depression [12,38]. Self-reported symptoms of insomnia independently increase risk of cognitive decline in older men [39]. Heart disease patients who sleep less than 5 hours a night have a threefold increase in myocardial infarction [40]. Blood sugar control worsens with insomnia. Similarly, chronic pain can lead to insomnia, and insomnia increases pain ratings [41,42]. A recent study demonstrated that worsening sleep apnea scores correlated with the development of depression [11]. Stimulants, including nicotine and coffee, cause insomnia and sleep disturbances. Decaffeinated coffee was developed to encourage coffee consumption while limiting sleep disturbance, and thus improve sales; however, the amount of caffeine varies by the product Table 1. Alcohol and a number of other drugs disrupt sleep. Alcohol disrupts sleep through several mechanisms. Although alcohol taken before sleep may promote sleep onset, it tends to shorten total sleep time, and can exacerbate other conditions, such as gastroesophageal reflux and sleep apnea, if taken in large quantities. Alcohol also is a diuretic, which may cause awakening for voiding. Alcohol withdrawal in a heavy drinker may be associated with restlessness or tremor. Consequences of insomnia Insomnia has significant direct and indirect costs on the individual, family or caregiver, and society. Insomnia causes or is associated with impaired cognitive functioning [28], negative quality of life measures [21], increased incidence of pain [21], poorer general health, increased future risk of psychiatric disorders [21,43], increased drug use [21,43], decreased

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Table 1 Common products and caffeine dose Brewed coffee (8 oz) Double espresso (2 oz) Instant coffee (8 oz) Decaf coffee (8 oz) Tea (8 oz) Coke (8 oz) Mountain Dew (8 oz) NoDoz, maximum strength (1 tablet) Excedrin (two tablets) Anacin (two tablets) Hershey’s Special Dark Chocolate Bar (1.5 oz) Hershey Milk Chocolate Bar (1.5 oz) Hot Chocolate (8 oz)

60–120 mg 45–100 mg 70 mg 1–6.5 mg 15–50 mg 26 mg 37 mg 100 mg 130 mg 64 mg 31 mg 5 mg 5 mg

job performance, increased absenteeism [44], increased risk of accidents [44], increased incidence of a number of medical problems, and worsening of existing medical problems [21]. Patients who have insomnia use health care more [19,45]. The economic costs of insomnia and associated morbidity are high; direct costs are estimated to be nearly $14 billion, and indirect costs such as missed work and decreased productivity are estimated to be nearly $28 billion [44].

Diagnosis The diagnosis of insomnia begins with suspicion and a good sleep history from the patient or family or caregivers. The accuracy of patient self-report and sleep studies have shown both over- and under-reporting problems with sleep [46]. Because insomnia is very prevalent, sleep quality questions should be included in all routine evaluation histories. In the 2000 National Sleep Foundation Survey of Primary Care Physicians, almost all responders agreed that a sleep history should be part of the routine visit; however, only 52% physicians conducted regular sleep assessments [47]. If a patient presents with complaints of fatigue, excessive daytime sleepiness, depressed or anxious mood, memory or concentration problems, or pain, a sleep history should be taken, because sleep problems are common with these complaints. A sleep history should include onset, frequency, duration, and severity of sleep complaints, and their fluctuations over time. Any precipitating event should be sought. Noise levels, activities, naps, eating, medications, stimulants, alcohol, or drugs taken throughout the 24hour period should be investigated. Determine if sleep difficulties involve initiation or maintenance of sleep. Inquire about any bedtime rituals or time in bed not sleeping, which may reveal sleep hygiene issues or conditioned insomnia.

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Inquire if specific symptoms occur around sleep onset, such as paresthesias, unpleasant sensation, and uncontrollable limb movements. Restless legs syndrome presents with a delay in sleep because the patient feels an uncomfortable sensation of the legs at rest. Iron deficiency, renal failure, pregnancy, and selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with restless legs syndrome [48]. Periodic leg movement disorder is noted in at least 80% of cases with restless legs syndrome [48]. Patients who have recurring periodic limb movements in sleep (PLMS) most commonly dorsiflex the ankles or flex the knees and hips, and occasionally the upper limbs, every 20 to 40 seconds. PLMS are more common in persons over age of 65; they may occur alone or in association with end-stage renal disease, tricyclic antidepressants, or monoamine oxidase inhibitors [49]. Sleeping partners may suggest the diagnosis, but a polysomnographic study confirms the diagnosis. Inquire about symptoms during sleep (repeated awakenings or early morning awakening, loud snoring, choking or gasping, cessation of breathing) or symptoms during the day (excessive fatigue, irritability, or difficulty concentrating). Previous treatments should also be noted. A sleep log, preferably over 2 weeks, may yield important information. Both current and past alcohol and drug history should be obtained. Ten to 15% of insomniacs are substance abusers [50]. Objective alterations in sleep architecture have been observed in alcoholics for 12 months of abstinence [12]. Patients who have drug abuse problems can have insomnia even 1 year after abstinence begins [12]. Furthermore, patients who have a previous history of alcohol or drug abuse who continue to have insomnia have higher relapse rates [51]. Although caffeine is a well-known drug that causes sleep disturbance, other drugs include nicotine, antidepressants (SSRIs, serotonin-norepinephrine reuptake inhibitors [SNRIs], bupropion, monoamine oxidase inhibitors [MAOIs]), opiates, corticosteroids, central nervous system stimulants (dextroamphetamine, methylphenidate), bronchodilators, pseudoephedrine, methyldopa, beta blockers, alpha blockers, and cholinesterase inhibitors [52,53]. A family history may suggest certain primary sleep disorders. About one third of patients who have idiopathic restless legs syndrome have a positive family history [48]. The medical, including psychiatric, history and physical examination are useful in identifying comorbid conditions. The most common comorbidity is a psychiatric diagnosis. Forty percent of chronic insomniacs have a coexisting psychiatric diagnosis [12]. More than half of persons who have depression, anxiety disorders, psychosomatic disorders, neuroses, dementia, and schizophrenia have insomnia complaints [38]. For most patients who have insomnia, the diagnosis is made with only a good history and a physical examination. Sleep diaries or sleep questionnaires may be helpful, but none have been standardized. The Epworth Sleepiness Scale may be used to determine the level of daytime sleepiness and if further evaluation is necessary.

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Although multichannel polysomnography is the most sensitive tool to differentiate wakefulness and sleep, it is not necessary for most cases of insomnia. Because it is expensive and can disrupt sleep, its use should be limited to cases in which sleep-related breathing problems such as sleep apnea are suspected. Patients who have daytime sleepiness, snoring, witnessed apneic spells, and a body mass index over 35 have a greater than 70% probability of having sleep apnea [54]. Patients who have these symptoms, narcolepsy, or sleepwalking should be referred for polysomnography. Additionally, patients who have daytime sleepiness, especially those with occupations such as pilot or truck driver, should have sleep studies done. A good history may uncover an important perceived insomnia caused by the variations in the periodicity of the biologic clocks that create the phenomenon of the ‘‘owl,’’ or type B, and the ‘‘lark,’’ or type A persons. These tendencies appear to be genetically predetermined, but may change over the life cycle. Adolescents tend to have a natural sleep phase delay, and are owls, up late and wanting to wake later, and the elderly tend to have a natural phase advance, and are larks who go to bed early and arise early. These variations are not true insomnia. Insufficient sleep syndrome probably represents the most common cause of excessive sleepiness in the general population. One third of normal adults appear to get inadequate sleep because of lifestyle choices or stimuli [55]. People who ‘‘choose’’ to sleep fewer than 7 hours a night because of working two jobs, staying up late watching television, studying, or carrying for a sick child, suffer from insufficient sleep, not insomnia. Management Four out of ten insomniacs self-medicate with an over-the-counter medicine or alcohol [56]. The most common treatments used by persons who have chronic insomnia are over-the-counter antihistamines, alcohol, and prescriptions medicines [56]. Over 11% of Americans report using either prescription (6%) or over-the-counter medicines (6%) at least a few nights each month to help them sleep, according to a 2002 Sleep in America Poll [56]. Treatments for insomnia are considered effective if they decrease sleep onset latency or increase total sleep time by 30 minutes. Most treatment studies use patient-reported sleep diaries to measure outcome. Criteria used include total sleep time, sleep-onset latency, and number of nocturnal awakenings. Recognized insomnia treatments include: (1) non pharmacologic (cognitive and behavioral therapy), and (2) pharmacologic, with three types of prescription medicines (benzodiazepines, nonbenzodiazepines, and antidepressants). Nonpharmacologic treatment Cognitive-behavioral therapies (CBTs) comprise several components: (1) cognitive understanding of sleep, (2) sleep hygiene, (3) relaxation training,

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(4) stimulus control, and (5) sleep restrictions. Cognitive therapy involves restructuring how a person views sleep; it dispels anxiety-producing beliefs and erroneous beliefs about sleep and sleep lost, such as the negative thoughts, ‘‘I will never get to sleep,’’ ‘‘I have a chemical imbalance that requires a pill to sleep,’’ or ‘‘If I don’t get to sleep now, I will have a terrible day tomorrow.’’ Many insomniacs feel powerless in their sleep struggles, and have poor understanding about their role in their insomnia. Improving sleep hygiene encourages behaviors that enhance sleep and avoids behaviors that interfere with sleep initiation or maintenance (a list of do’s and don’ts) Box 1. The third component of CBT is relaxation training, which can reduce the physiological and cognitive arousal at bedtime that often interferes with sleep initiation. Techniques include progressive muscle relaxation, meditation, and yoga. These techniques have been shown to be effective compared with the age-old ‘‘counting sheep.’’ Stimulus control, the fourth component of CBT, involves re-establishing the bedroom for only sleep (and sex). One should not watch television, listen to music or audio tapes, check e-mail, answer cell phones, solve family problems, or read in bed. If one is not asleep within 20 minutes of lying down, one is to leave the bed and do quiet activities in another room. One returns to bed only when tired. The process is repeated until sleep is initiated. The final component is sleep restrictions. The patient determines how much sleep is needed and then restricts time in bed with rigid bed and rise times, even if sleep wasn’t successful the night before. Daytime naps are

Box 1. Sleep hygiene: a list of do’s and don’ts Do’s Regular exercise in morning or afternoon Relaxing bedtime activities Increase bright light during the day Comfortable sleep environment: dark, cool, quiet, safe, comfortable bed Warm bath before bed Wear socks to bed Don’ts No strenuous exercise 3 hours before bed No eating or drinking 3 hours before bed No stimulants: caffeine or nicotine No alcohol No daytime napping Limit bright light at night No clock in bedroom

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discouraged because they may aggravate the following nights’ sleep problems. These times should also be followed on the weekends. CBTs have been shown to be effective for the treatment of chronic insomnia in randomized controlled trials [57]. Therapy is less expensive than medications, benefits last beyond the therapy, and there are no adverse side effects. Stimulus control therapy was found effective and superior to progressive muscle relaxation, imagery training, and paradoxical intention (prohibiting sleep until a certain hour). Progressive muscle relaxation was superior to placebo. Although CBTs have demonstrated efficacy, few clinicians are skilled in them, and therefore they are not in widespread use. Physicians are more apt to write a prescription than counsel in CBTs or refer to someone who is trained in CBTs. Other proposed insomnia treatments include tai chi, which may improve sleep quality (level 2 evidence) in inactive adults greater than 60 years old [58]. A program of regular exercise may be useful in the treatment of patients who have sleep disorders. Warm baths before bed, wearing socks to bed (proposed to improve sleep by improving vasodilatation), yoga, acupuncture, and light therapy have not been adequately evaluated. Pharmacologic treatment The Food and Drug Administration (FDA) has approved eight medications for insomnia, and seven are approved for 35 days or less. Only the recently FDA-approved eszopiclone (Lunesta) has no restriction on duration of use [59]. Yet an estimated 0.5% of the population takes sedative medications nightly for insomnia for more than 1 year [60]. Benzodiazepine receptor agonists fall into two broad groups of prescription hypnotics: (1) benzodiazepinesdestazolam (Prosam), flurazepam (Dalmane), quazepam (Doral), temazepam (Restoril), and triazolam (Halcion); and (2) the more recent agents that act at benzodiazepine receptors, but have nonbenzodiazepine structuresdzaleplon (Sonata), zolpidem (Ambien), and eszopiclone (Lunesta). Several studies [61–63] show that benzodiazepines and nonbenzodiazepines are effective in the short-term management of insomnia; however, with the exception of eszopiclone, long-term use of either benzodiazepines or nonbenzodiazepines has not been studied using randomized controlled trials. Furthermore, all of these medications have adverse effects, including daytime sedation, cognitive impairment, motor incoordination, dependence, and rebound insomnia, and the problems are more pronounced in the elderly [61]. In a meta-analysis of hypnotics in the elderly [63], sedatives were associated with a statistically significant improvement in sleep quality (number needed to treat 13). Although effective, adverse effects were significant (number needed to harm was 6). The most common adverse reports were fatigue, headache, nightmares, and nausea. Cognitive effects, including memory loss and confusion, daytime fatigue, and impairment of performance tasks, were significantly more common with sedative use (number

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needed to harm 22). Psychomotor problems were more common with sedative use, including seven serious falls and one motor vehicle collision, but the difference did not reach statistical significance [62]. Sedative hypnotics are associated with a small improvement in some aspects of sleep in older patients, but this therapy also carries significant risk of adverse events. Sedative-hypnotics are not recommended in the elderly because risks may outweigh benefits (Grade B recommendation). In 2007, the FDA requested that all manufacturers of sedative-hypnotic drug products (Ambien/Ambien CR, Butisol Sodium, Carbrital, Dalmane, Doral, Halcion, Lunesta, Placidyl, Prosom, Restoril, Rozerem, Seconal, and Sonata), strengthen their product labeling to include stronger language concerning potential risks. These risks include severe allergic reactions and complex sleep-related behaviors, which may include sleep driving. Sleep driving is defined as driving while not fully awake after ingestion of a sedative-hypnotic product, with no memory of the event. The use of short-acting agents does not appear safer than long-acting agents. Zolpidem (Ambien) or zaleplon has a shorter duration of action than benzodiazepines and proposed fewer adverse effects, but there are no direct comparison trials. In one study [63], zolpidem (Ambien) use was associated with significant increased risk of hip facture (adjusted odd ratio, [AOR] 1.95) compared with benzodiazepines (AOR 1.46) and antipsychotics (AOR 1.61). Because of these risks of hypnotics, physicians have changed their prescribing practices for insomnia in the past 20 years from benzodiazepines to antidepressants [64]. Trazodone (Desyrel) is now the most commonly prescribed medication for insomnia in the United States [62]. Trazodone is sedating and improves several sleep parameters; however, there is no long term use study of trazodone or other antidepressants for chronic insomnia. Further, some antidepressants, such as the SSRIs, may cause insomnia. Also, the tricyclics may worsen restless legs syndrome and periodic limb movements [49]. More sedating antidepressants have been prescribed in low doses for insomnia. In the absence of clinical depression, the evidence to support the use of antidepressants for chronic insomnia is less clear. The FDA recently approved ramelteon (Rozerem), a melatoninin receptor agonist for persons having problems falling asleep. No published studies have compared ramelteon with melatonin, which is over-the-counter and much less expensive. The biological action of ramelteon is similar to melatonin and nonaddictive. The prescription ramelteon product is more likely to be pure. In a couple of randomized trials of short duration (5 weeks or less) with placebo, ramelteon demonstrated improved sleep latency (8 minutes average) in patients 65 years and older who had chronic insomnia [65,66]; however, in patients younger than 65 there was no difference in sleep parameters between ramelteon and placebo [66]. The expense of the drug (more than $90 per month) may not be worth the small benefit, if any, in getting to sleep. Although most medications are discouraged in pregnancy, especially in the first trimester, the FDA Pregnancy Category ratings B for zolpidem

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(Ambien), C for zaleplon, eszopiclone and ramelteon, and Category D or X for all benzodiazepines [59]. A recent meta-analysis [67] found no difference in outcomes between pharmacotherapy and behavioral therapy, except that behavioral therapy more significantly decreased sleep latency, was less expensive, and had fewer side effects. In the only randomized controlled trial [68] of CGT versus zopicolone, however, CBT was superior to zopicolone in most outcomes. Zopiclone did not differ from placebo in either short-term or long-term (6 months) evaluations. Measured outcomes included both sleep diaries and polysomnographic data. Although CBT has more lasting effect, pharmacotherapy has a more rapid onset, and may be used if the patient will benefit from the more rapid effect of drug therapies while pursuing behavior modifications. For peri/postmenopausal women who have insomnia, a randomized controlled trial [69] found that eszopiclone provided significant improvements in sleep, and positively impacted mood, quality of life, and menopauserelated symptoms. A number of unapproved medications have been used for the treatment of insomnia. Antihistamines such as diphenhydramine (Benadryl) are the most commonly used over-the-counter treatment for insomnia, although there is no evidence for efficacy. The elderly especially have significant adverse effects from these medicines, including daytime sedation, diminished cognitive function, and delirium, as well as dry mouth, blurred vision, urinary retention, constipation, and risk of increased intraocular pressure in persons who have narrow angle glaucoma. Several herbal products such as L-tryptophan, melatonin, and valerian have been touted to improve sleep. Melatonin may be helpful in a subset of insomnia patients. There is no known risk of harm, although long-term use has not been studied. Melatonin, a natural hormone produced by the pineal gland, plays a role in the control of circadian rhythms. Because melatonin is not regulated by the FDA and concentrations vary in strength, studies are difficult. Melatonin was shown to be effective over placebo in the treatment of circadian rhythm disorders (jet lag) [69], but its effectiveness for chronic insomnia or an effective dose is undetermined. Valerian is derived from the root of the plant valeriana, and also is not regulated by the FDA. Limited studies do not show any benefit when compared with placebo in chronic insomnia. Further, the case reports of hepatotoxicity are troubling. There is not sufficient evidence on the effectiveness or safety of L-tryptophan in the management of chronic insomnia. Consensus groups from Canada, England, and the United States have all proposed clinical guidelines for the management of chronic insomnia [70– 72]. Treatment of insomnia should be individualized based on the nature and severity of symptoms. Causes and comorbidities should be sought and treated. If insomnia persists, cognitive and behavioral therapies should be started first; pharmacologic treatment should be considered an adjunct

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treatment for insomnia, and prescribed for short-term use only. Patients who have insomnia need regular follow-up like those who have other chronic conditions Box 2. Summary Sleep is a good indicator of health. Sufficient sleep, like nutrition and exercise, is an essential component of a healthy lifestyle. Although sleep problems are common, they are often undiagnosed; patients who have insomnia seldom volunteer their concerns with their physician. Insomnia can usually be diagnosed with clinical suspicion and complete histories and examinations. Sleep problems often coexist with psychiatric and medical conditions. The initial treatment of chronic insomnia most often should be cognitive and behavioral therapies. Clinicians need to either become skilled in the behavioral treatments, or refer to providers who can offer these valuable

Box 2. Treatment guidelines of insomnia 1. Determine if insomnia causes daytime problems for patient or caregiver. 2. Identify and treat the causes of insomnia if present. 3. If insomnia persists, use behavioral treatments first (learn how to counsel or where to refer patient). 4. Use pharmacologic treatment only if Behavioral treatment is ineffective or the person is unwilling to try or unable to do Person is suffering insomnia-related distress and beginning behavioral therapy Insomnia is temporary or short-term Insomnia is expected or occurs with known condition (use of steroids) or event (traveling across time zones), and course is limited 5. If prescribing hypnotic, prescribe For short periods only (few days or intermittent 3/wk) Lowest effective dose Cheapest (no firm evidence of differences in the effects of zaleplon, zolpidem (Ambien), zopiclone, and the shorter-acting benzodiazepines) Don’t prescribe a different one if first doesn’t work unless a side effect 6. Close follow-up whether behavioral, pharmacologic treatment, or both given 7. Refer if insomnia persists

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treatments. If pharmacologic treatment is needed, careful guidelines should be adhered to minimize harm. Since The National Center on Sleep Disorders Research was established in 1993, sleep and sleep disorders are better understood, but much work remains to be done to understand the mechanisms that link sleep to health and how we can improve both for our patients.

References [1] National Sleep Foundation. Sleep in America poll. Washington, DC: National Sleep Foundation. 2005. [2] Pearson NJ, Johnson LL, Nahin RL. Insomnia, trouble sleeping, and complementary and alternative medicine: analysis of the 2002 National Health Interview Survey data. Arch Intern Med 2006;166(16):1775–82. [3] Almeida OP, Pfaff JJ. Sleep complaints among older general practice patients: association with depression. Br J Gen Pract 2005;55(520):864–6. [4] Archbold KH, Pituch KJ, Panahi P, et al. Symptoms of sleep disturbances among children at two general pediatric clinics. J Pediatr 2002;140(1):97–102. [5] Johnson EO, Roth T, Schultz L, et al. Epidemiology of DSM-IV insomnia in adolescence: lifetime prevalence, chronicity, and an emergent gender difference. Pediatrics 2006;117(2): e247–56. [6] Ancoli-Israel S, Roth T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. Sleep 1999;22(2):S347–53. [7] American Psychiatric Task Force on DMS-IV. Diagnosis and statistical manual of mental disorders: DSM-IV. Washington, DC: American Psychiatric Association; 1994. [8] Sateia MJ, Nowell PD. Insomnia. Lancet 2004;364:1959–73. [9] Graeber RC. Jet lag and sleep disruption. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. Philadelphia: WB Saunders; 1994. p. 463–70. [10] Zee PC, Turek FW. Sleep and health: everywhere and in both directions. Arch Intern Med 2006;166:1686–8. [11] Peppard PE, Szklo-Coxe M, hia KM, et al. Longitudinal association of sleep related breathing disorder and depression. Arch Intern Med 2006;66:1709–15. [12] Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders: an opportunity for prevention? JAMA 1989;262:1479–84. [13] Breslau N, Roth T, Rosenthal L, et al. Sleep disturbances and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry 1996;39:411–8. [14] Balter MB, Uhlenhuth EH. New epidemiologic findings about insomnia and its treatment. J Clin Psychiatry 1992;53:S34–9. [15] Katz DA, McHorney CA. Clinical correlates of insomnia in patients with chronic illness. Arch Intern Med 1998;158(10):1099–107. [16] Hauri PJ, Fisher J. Persistent psychophysiologic (learned) insomnia. Sleep 1986;9:38–53. [17] Gislason T, Reynisdottir H, Krisbjarnarson H, et al. Sleep habits and sleep disturbances among the elderlydan epidemiological survey. J Intern Med 1993;234(1):31–9. [18] Roberts RE, Shema SJ, Kaplan GA. Prospective data on sleep complaints and associated risk factors in an older cohort. Psychosom Med 1999;61(2):188–96. [19] Ohayon M. Epidemiological study on insomnia in the general population. Sleep 1996; 19(3 Suppl):S7–15. [20] Mellinger GD, Balter MB, Uhlenhuth EH. Insomnia and its treatment. Arch Gen Psychiatry 1985;42(3):225–32. [21] Simon GE, Vonkorff M. Prevalence, burden, and treatment of insomnia in primary care. Am J Psychiatry 1997;154(10):1417–23.

672

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[22] Foley D, Ancoli-Israel S, Britz P, et al. Sleep disturbances and chronic diseases in older adults: results of 2003 National Sleep Foundation Sleep in America Survey. J Psychosom Res 2004;56(5):497–502. [23] Kupperman M, Lubeck DP, Mazonson PD, et al. Sleep problems and their corelates in a working population. J Gen Intern Med 1995;10:25–32. [24] Zammit GK, Weiner J, Damato N, et al. Quality of life in people with insomnia. Sleep 1999; 22(2):S379–85. [25] McMurray SM, Vitello MV, Gibbons LE, et al. Factors associated with caregiver reports of sleep disturbances in persons with dementia. Am J Geriatr Psychiatry 2006; 14:112–20. [26] Ancoli-Israel S, Parker L, Sinaee R, et al. Sleep fragmentation in patients from a nursing home. J Gerontol 1989;44:M18–21. [27] Bixler EO, Scharf MB, Soldatos CR, et al. Effects of hypnotic drugs on memory. Life Sci 1979;25(16):179–88. [28] Janson C, Linberg E, Gislason T, et al. Insomnia in menda 10 year prospective population based study. Sleep 2001;24(4):425–30. [29] Ohayon MM, Zulley J, Guilleminault C, et al. How age and daytime activities are related to insomnia in the general population: consequences for older people. J Am Geriatr Soc 2001; 49(4):360–6. [30] Foley DJ, Monjan A, Simonsick EM, et al. Incidence and remission of insomnia among elderly adults: an epidemiologic study of 6800 persons over three years. Sleep 1999;22(Suppl 2): S366–72. [31] Benca RM, Ancoli-Israel S, Moldofsky H. Special considerations in insomnia diagnosis and management: depressed, elderly, and chronic pain populations. J Clin Psychiatry 2004; 65(Suppl 8):26–35. [32] Kravitz HM, Janssen I, Santoro N, et al. Relationship of day-to-day reproductive hormone levels to sleep in midlife women. Arch Intern Med 2005;165(20):2370–6. [33] Santiago JR, Nolledo MS, Kinzler W, et al. Sleep and sleep disorders in pregnancy. Ann Intern Med 2001;134(5):396–408. [34] Meltzer LJ, Mindell JA. Impact of child’s chronic illness on maternal sleep and daytime functioning. Arch Intern Med 2006;166:1749–55. [35] Ohayon MM. Severe hot flashes are associated with chronic insomnia. Arch Intern Med 2006;166(12):1262–8. [36] Diagnostic Classification Steering Committee. The International classification of sleep disorders, revised: diagnostic and coding manual. Rochester (MN): American Sleep Disorders Association; 1997. [37] Reid S, Dwyer J. Insomnia in HIV infection: a systematic review of prevalence, correlates, and management. Psychosom Med 2005;67(2):260–9. [38] Roth T. The relationship between psychiatric diseases and insomnia. Int J Clin Pract 2001; 116(Suppl):3–8. [39] Cricco M, Simonsick EM, Foley DJ. The impact of insomnia on cognitive functioning in older adults. J Am Geriatr Soc 2001;49(9):1185–9. [40] Liu Y, Tanaka H. Overtime work, insufficient sleep, and risk of non fatal acute myocardial infarction in Japanese men. Occup Environ Med 2002;59:47–51. [41] Drewes AM, Svedsen L, Taagholt SJ, et al. Sleep in rheumatoid arthritis: a comparison with healthy subjects and studies of sleep/wake interactions. Br J Rheumatol 1998;25: 1191–7. [42] Harding SM. Sleep in fibromyalgia patients: subjective and objective findings. Am J Med Sci 1998;315:367–76. [43] Leger D, Guilleminault C, Bader G, et al. Medical and socio-professional impact of insomnia. Sleep 2002;25(6):625–9. [44] Walsh JK. Clinical and socioeconomic correlates of insomnia. J Clin Psychiatry 2004; 65(Supp 16):41–5.

INSOMNIA: AN IGNORED HEALTH PROBLEM

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[45] Hatoum HT, Kania CM, Kong SX, et al. Prevalence of insomnia: a survey of enrollees in five managed care organizations. Am J Manag Care 1998;4:79–86. [46] Carskadon MA, Dement WC, Mitler MM, et al. Self-reports versus sleep laboratory findings in 122 drug-free subjects with complaints of chronic insomnia. Am J Psychiatry 1976;133: 1382–8. [47] National Sleep Foundation. Survey of primary care physicians. Available at: http://www. sleepfoundation.org. [48] Montplaisir J, Boucher S, Poirier G, et al. Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria. Mov Disord 1997;12:61–5. [49] Walsh JK, Benca RM, Bonnet M, et al. Insomnia: assessment and management in primary care. National Heart, Lung, and Blood Instititue Working Group on Insomnia. Am Fam Physician 1999;59:3029–38. [50] Meyer TJ. Evaluation and management of insomnia. Hosp Pract 1998;33:75–8, 83–6. [51] Brower KJ, Aldrich MS, Robinson EA, et al. Insomnia, self medication and relapse to alcoholism. Am J Psychiatry 2001;158(3):399–404. [52] Ancoli-Israel S. All I want is a good night’s sleep. Chicago: Mosby-Year Book Inc.; 1996. [53] Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly. an update. Arch Intern Med 1997;157(14):1531–6. [54] American Sleep Disorders Association. Practice parameters for the use of portable recording in the assessment of obstructive sleep apnea. Standards of Practice Committee of the American Sleep Disorders Association. Sleep 1994;17:372–7. [55] Bonnet MH, Arand DL. We are chronically sleep deprived. Sleep 1995;18:908–11. [56] National Sleep Foundation. Sleep in America poll. 2002. Washington, DC: National Sleep Foundation. [57] Irwin MR, Cole JC, Nicassio PM. Comparative meta-analysis of behavioral interventions for insomnia and their efficacy in middle-aged adults and in older adults 55þ years of age. Health Psychol 2006;25(1):3–14. [58] Li R, Fisher KJ, Harmer P, et al. Tai chi and self-rated quality of sleep and daytime sleepiness in older adults: a randomized controlled trial. J Am Geriatr Soc 2004;52(5):892–900. [59] Treatment guidelines from the medical letter. The Medical Letter on Drugs and Therapeutics. 2006;4(42):5. [60] National sleep Foundation. Sleep in America poll. Data from 1997 and 2001, 2002 sleep poll. Available at: http://www.sleepfoundation.org/im/2002SleepinAmericaPoll.pdf. [61] Holbrook AM, Crowther R, Lotter A, et al. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 2000;162:225–33. [62] Glass J, Lanctot KL, Herrmann N, et al. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ 2005;331:1169–73. [63] Gray SL, LaCroix AZ, Hanlon JT, et al. Benzodiazepine use and physical disability in community-dwelling older adults. J Am Geriatr Soc 2006;54(2):224–30. [64] Roth T, Seiden D, Sainati S, et al. Effects of ramelteon on patient-reported sleep latency in older adults with chronic insomnia. Sleep Med 2006;7(4):312–8. [65] Ramelteon Ramelteon (Rozerem) [package insert]. Lincolnshire (IL): Takeda Pharmaceuticals North America; 2005. Available at: http://www.fda.gov/cder/foi/label/2005/021782lbl. pdf. Accessed August 8, 2005. [66] Smith M, Perlis ML, Park A, et al. Comparative meta-analysis of pharmacotherapy and behavior therapy for persistent insomnia. Am J Psychiatry 2002;159:5–11. [67] Sivertsen B, Omvik S, Pallesen S, et al. Cognitive behavioral therapy vs zopiclone for treatment of chronic primary insomnia in older adults: a randomized controlled trial. JAMA 2006;295(24):2851–8. [68] Soares CN, Joffe H, Rubens R, et al. Eszopiclone in patients with insomnia during perimenopause and early postmenopause: a randomized controlled trial. Obstet Gynecol 2006; 108(6):1402–10.

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[69] Buscemi N, Vandermeer B, Hooton PR, et al. Melatonin for treatment of sleep disorders. Evidence report/technology assessment No 108. AHRQ Publication No. 05-E002-1. Rockville (MD): Agency for Healthcare Research and Quality; 2004. [70] National Institutes of Health State-of-the-Science Conference statement: Manifestations and management of chronic insomnia in adults. 2005. Available at: http://concensus.nih. gov/2005/2005InsomniaSOS026html.htm [71] Buscemi N, Vandermeer B, Friesen C, et al. Manifestations and management of chronic insomnia in adults. Evidence report/technology assessment. Agency for Healthcare Research and Quality 2005;125:1–11. [72] National Institute for Clinical Excellence (NICE). Zaleplon, zolpidem and zopiclone for short-term management of insomnia. Available at: http://www.nice.org.uk.