Pharmacologic Treatment of Body Dysmorphic Disorder

Transcription

1 Pharmacologic Treatment of Body Dysmorphic Disorder Sallie Jo Hadley, MD, Suah Kim, BA, Lauren Priday, MA, and Eric Hollander, MD CLINICAL FOCUS Primary Psychiatry. 2006;13(7):61-69 ABSTRACT Compared to other psychiatric disorders, pharmacologic treatment research for body dysmorphic disorder (BDD) is in the early stages. Consequently, there are no medications with a Food and Drug Administration indication for the treatment of BDD. Evidence from case reports, retrospective reviews, open-label studies, and a growing number of controlled trials have consistently demonstrated seoronin reuptake inhibitor (SRI) superiority over other psychotropic medications for the treatment of BDD. Thus, SRIs are usually the first-line choice of pharmacologic treatment for BDD. In general, higher doses than used for treating other disorders are needed to treat BDD. Also, a longer time interval of treatment may be required before a clinical response to the SRI is evident. In fact, some BDD experts suggest that up to 12 weeks of SRI treatment with at least 2 4 weeks of the total treatment at the highest recommended dose (and tolerated by the patient) should be given before determining that an SRI is ineffective. Use of SRIs for treatment of BDD along with comorbid mood, anxiety, eating, substance abuse, or impulsecontrol disorders can be challenging. Choice and dose of a particular SRI may be affected by the other medications used to target comorbidity. If BDD symptoms remain refractory to SRI pharmacotherapy, reported strategies for achieving symptom reduction include augmenting the SRI with another psychotropic medication (or cognitive-behavioral therapy), or switching to a different SRI or psychotropic medication. FOCUS POINTS Body dysmorphic disorder (BDD) symptoms interfere with daily functioning and quality of life and cause significant emotional distress. Goals for BDD pharmacotherapy include reduction of symptoms, such as excessive time spent preoccupied with appearance concerns or time spent engaged in appearance-related behaviors. Research and clinical evidence support the use of serotonin reuptake inhibitors (SRIs) over other medications as first-line treatment of BDD. Comorbid psychiatric disorders with BDD are common and frequently lead to misdiagnosis of BDD. Clinical evidence supports the use of SRIs and other psychotropic medications to target both BDD and comorbid symptoms. When BDD symptoms persist despite appropriate dosing and duration of SRI monotherapy, augmentation of the SRI with other psychotropics (or cognitive-behavioral therapy), as well as switching to a different SRI, may be of benefit. INTRODUCTION The main goal of pharmacologic treatment of body dysmorphic disorder (BDD) is to reduce core features of BDD so as to improve daily functioning, relieve emotional distress, and enhance overall quality of life. 1 Symptom reduction usually refers to decreasing the amount of time Dr. Hadley is assistant professor of psychiatry, Ms. Kim is clinical research coordinator in the Compulsive and Impulsive Disorders Program, Ms. Priday is senior research clinical coordinator for the Department of Psychiatry, and Dr. Hollander is Esther and Joseph Klingenstein Professor and chair at Mount Sinai School of Medicine in New York City. Disclosure: Drs. Hadley, Ms. Kim, and Ms. Priday report no affiliation with or financial interest in any organization that may pose a conflict of interest. Dr. Hollander has received grant support from the Food and Drug Administration. Please direct all correspondence to: Sallie Jo Hadley, MD, Department of Psychiatry, Mount Sinai School of Medicine, Atran E level, Rm 25, One Gustave Levy Place, New York, NY 10029; Tel: ; Fax: ; salliejo.hadley@mssm.edu. Primary Psychiatry MBL Communications 61

2 S.J. Hadley, S. Kim, L. Priday, E. Hollander spent obsessing or being preoccupied with appearance concerns, as well as the amount of time and emotional energy spent engaged in appearance-related compulsive behaviors. Usually, the compulsive behaviors are aimed at coping with anxiety related to appearance or are an attempt to hide, correct, or camouflage a perceived appearance flaw. 2-4 The obsessive thoughts and associated compulsive behaviors typical of BDD can lead to poor functioning in academics, occupations, and relationships. Social withdrawal is common. BDD symptoms as well as the effect of BDD on a person s life can lead to significant emotional despair. Not surprisingly, rates of attempted and completed suicide are high among patients with BDD. 5 Patients with symptoms characteristic of BDD have been described in the literature for 130 years; however, not until 1987 was BDD considered a psychiatric disorder. 6 Over the past 20 years, clinical and research interest in BDD has increased dramatically. However, compared to treatment research for other psychiatric disorders, treatment for BDD is understudied. This article discusses approaches to the pharmacologic treatment of BDD, including the delusional variant; practical aspects of using serotonin reuptake inhibitors (SRIs) to treat BDD; BDD pharmacotherapy in the context of other psychiatric comorbidity; and options for treatment when patients with BDD are refractory to SRI pharmacotherapy. PHARMACOLOGIC TREATMENT OF BODY DYSMORPHIC DISORDER The goal of pharmacologic treatment of BDD is to decrease the amount of time engaged in appearance preoccupations and associated compulsive behaviors, which can impair daily functioning, cause emotional distress, and result in a poor quality of life. Compared with other psychiatric disorders, research investigating the efficacy of pharmacotherapy for BDD is lacking. The majority of studies that have been conducted stemmed from case reports describing BDD symptom improvement following treatment with clomipramine 7-11 or SRIs. 1-3,8 As outlined in the Table, SRIs or clomipramine have demonstrated efficacy in symptom reduction for BDD, including the delusional variant of BDD. Since there are no medications with a Food and Drug Administration indication for the treatment of BDD, use of SRIs, clomipramine, or any medication to treat BDD, would be considered off-label. SEROTONIN REUPTAKE INHIBITOR TREATMENT OF BODY DYSMORPHIC DISORDER Clinical evidence and the studies described in the Table support SRIs as the first-line choice of pharmacotherapy for BDD. 2-4,12-19 Although the focus of this article concerns pharmacotherapy for BDD, it should be noted that cognitivebehavioral therapy (CBT) is also an effective monotherapy for BDD Preliminary evidence also suggests that the combination of SRIs with CBT may be an effective approach for management of BDD. 4,22 Though SRIs have shown benefit in BDD symptom reduction for some patients, it is clear that many patients fail to respond or only partially respond to SRI treatment. Factors affecting response to treatment include extremely stressful circumstances, side effects of SRIs, comorbid symptoms, substance abuse, noncompliance, and significant delusions Strategies for managing patients who fail to respond adequately to SRIs are discussed in the following sections. Dosing and Duration of Serotonin Reuptake Inhibitor Pharmacotherapy Similar to obsessive-compulsive disorder (OCD), BDD is characterized by intrusive appearance preoccupations and appearance-related compulsive behaviors. Like OCD, the dose of SRI needed to treat BDD is usually higher than doses required for treatment of depression. Additionally, the length of time required for a clinical response to SRI treatment may be much longer for BDD and OCD than for depression. 1-4,19 In fact, most BDD experts suggest that SRI treatment be given for a minimum of 12 weeks with at least 2 4 weeks of treatment at the highest dose tolerated by the patient (and recommended by manufacturer) before determining that a particular SRI treatment is ineffective. 1-4,19,26-28 Side Effects of Serotonin Reuptake Inhibitors In general, SRIs are well tolerated. However, side effects from SRIs, including headache, gastrointestinal distress, decreased libido, and decreased sexual functioning, may affect compliance with treatment. Most of the side effects, such as gastric discomfort or headache, occur early in treatment and resolve rather quickly. For the sexual side effects, augmentation of the SRI with bupropion, cyproheptadine, mirtazapine, or sildenafil may be helpful in restoring sexual function. 29,30 Primary Psychiatry MBL Communications 62

3 Pharmacologic Treatment of Body Dysmorphic Disorder MANAGEMENT OF BODY DYSMORPHIC DISORDER AND COMORBID DISORDERS BDD symptoms are similar to symptoms of other disorders. This accounts for some of the failure of clinicians to detect and adequately treat BDD. In particular, BDD is often comorbid with delusional disorder, depression, OCD, social anxiety disorder (SAD), certain personality disorders, eating disorders, substance abuse, and impulse-control disorders The treatment of BDD in the context of comorbid disorders is not straightforward, particularly since there are few controlled trials examining the efficacy of pharmacotherapy to treat BDD in the context of comorbidity. The following sections will draw from clinical evidence and published research to suggest possible strategies for treating BDD patients who have comorbid symptoms. Body Dysmorphic Disorder and Delusional Disorder According to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) 36 criteria, patients with BDD who lack insight, have referential thinking, and have very fixed delusions are double-coded with a diagnosis of BDD as well as delusional disorder, somatic type. 1-7,19,31-35,50 TABLE STUDIES INVESTIGATING PHARMACOLOGIC TREATMENTS FOR BODY DYSMORPHIC DISORDER Study Design Medication Outcome Measure Result Highlights Perugi et al 12 (1996) Phillips et al 13 (1998) Hollander et al 14 (1999) Phillips et al 15 (2002) Phillips and Najjar 16 (2003) Phillips 17 (2006) Open label 10 weeks n=15 Open label 16 weeks n=30 Double-blind, crossover, flexible dose 8 weeks/8 weeks n=29 Double-blind, placebo-controlled 12 weeks n=67 Open label 12 weeks n=15 Open label 15 weeks n=15 Fluvoxamine Average dose: 208±63.4 Fluvoxamine Average dose: 238±85 Clomipramine Average dose: 138±87 mg Desipramine Average dose: 147±80 Fluoxetine vs. placebo Average dose: 77±8 Citalopram Average dose: 51±16.9 Escitalopram Average dose: 28±6.5 BDD Hopkins Severity Scale Checklist Y-BOCS adapted for BDD (BDD Y-BOCS), CGI, HAM-A, BABS (delusionality scale) Primary: BDD/YBOCS, BDDadapted NIMH Global Obsessive- Compulsive Scale, CGI Secondary: Fixity of Beliefs modified for BDD Primary: BDD/Y-BOCS, CGI BABS Secondary: SF-36 QOL CGI-BDD BDD/Y-BOCS Secondary: SF-36 QOL CGI-BDD BDD/Y-BOCS, QOL Significant improvement in BDD symptoms for 10 of 12 subjects 1 subject discontinued, GI distress 3 subjects with minimal improvement Significant improvement from baseline for BDD- YBOCS, HAM-A, CGI 5 delusional subjects at baseline no longer delusional at endpoint Clomipramine significantly more effective than desipramine for all primary outcome measures Delusional subjects improved during clomipramine treatment just as much as nondelusional subjects Fluoxetine significantly more effective than placebo for all primary outcome measures No delusional subject responded to placebo QOL improved 66% of subjects considered responders on CGI 75% of subjects responders on BDD/Y-BOCS (P<.001) QOL improved during citalopram treatment 11/15 had significant improvement in BDD symptoms by weeks Significant improvement in delusionality and depressive and QOL measures BDD=body dysmorphic disorder; GI=gastrointestinal; Y-BOCS=Yale-Brown Obsessive-Compulsive Scale; CGI=Clinical Global Improvement; HAM-A=Hamilton Rating Scale for Anxiety; BABS=Brown Assessment of Beliefs; NIMH=National Institute of Mental Health; vs.=versus; SF-36=36-Item Short-Form; QOL=quality of life. Hadley SJ, Kim S, Priday L, Hollander E. Primary Psychiatry. Vol 13, No Primary Psychiatry MBL Communications 63

4 S.J. Hadley, S. Kim, L. Priday, E. Hollander Patients with delusional BDD have higher rates of impulsivity, substance abuse, and cluster B personality traits, which may contribute to the higher rates of suicide attempts reported among delusional BDD patients compared to nondelusional BDD patients. 5,50 For most psychotic disorders, antipsychotics are a logical choice of treatment. 53 However, in the treatment of BDD, including the delusional variant, the benefits of antipsychotic treatment remain unclear. Early case series and retrospective reviews lacked reliable and valid measures for delusional symptoms, and clinical judgment was used to report the efficacy of antipsychotics such as pimozide, olanzapine, risperidone, and clozapine in the treatment of BDD. 1-3,51,52 Though these early reports of antipsychotic efficacy for treating BDD were favorable and promising, the studies were limited by their retrospective nature and the lack of detail in defining criteria used to determine delusional symptoms and severity. More recent studies have begun to examine the efficacy of antipsychotics as augmentation agents for SRIs in treating BDD. One study examined the efficacy of pimozide versus placebo augmentation of fluoxetine-treated patients with BDD. 71 Patients receiving treatment with the SRI fluoxetine were randomized to pimozide versus placebo. At endpoint, there was no difference in symptom reduction between placebo and pimozide augmentation groups, and no improvement compared to fluoxetine monotherapy. Another small study examined the efficacy of olanzapine (open label) augmentation for BDD patients treated with fluoxetine, and again reported that olanzapine augmentation did not lead to a significant improvement in symptoms. 72 Of note, in the olanzapine study, two patients (of a total sample of six) did show some improvement to olanzapine augmentation. Given that emotional distress and mood lability are common among BDD patients, it is conceivable that the mood-stabilizing effects as opposed to the antipsychotic effects of olanzapine led to symptom reduction for the two patients. Clearly, larger placebo-controlled studies are needed to determine the role and mechanisms by which antipsychotics may be helpful in the treatment of BDD. Depression The most common comorbid disorder with BDD is depression. 33,35,37-44 Whether depression consistently precedes BDD or vice versa remains unclear. When initially seeking psychiatric treatment, >60% of BDD patients are depressed. Given that the BDD patient often feels ashamed or embarrassed about appearance concerns, unless specifically asked, they are likely not to report symptoms of BDD In fact, BDD patients often report fears of being labeled vain or superficial if they disclose the severity of their appearance concerns. The hesitancy of BDD patients in disclosing symptoms is illustrated by a recent study describing details of 122 patients consecutively admitted to an inpatient facility for suicidal ideation. 48 The admitting and discharge diagnosis for the 122 patients was major depressive disorder. Of the 122 admissions, 16 of the inpatients had well-established BDD (13%). Upon discharge, none of the 16 patients with BDD had been identified or diagnosed. The BDD patients reported that no one inquired about their appearance preoccupations, and they would not volunteer this information unless asked. For the majority of these 16 cases, BDD concerns precipitated suicidal ideation and led to the inpatient admission. BDD comorbid with depression has serious clinical implications. The highest rates of suicide ideation are among BDD patients with comorbid depression. 5,28,39,47 Failure to identify BDD among depressed patients has serious implications, since treatments which are effective for depression are often not effective for BDD. Specifically, depression responds to a wide variety of psychotropics such as SRIs, tricyclics, serotonin norepinephrine reuptake inhibitors, norepinephrine reuptake inhibitors, lithium, stimulants, and bupropion. Except for SRIs and clomipramine, none of the above medications have been found to be particularly effective for BDD. 1-5,19,28 Obsessive-Compulsive Disorder If BDD is comorbid with OCD, use of SRIs can be used effectively to treat both disorders. Usually, the required dose for the SRI is higher than the SRI dose required for depression. 19,22,28,37,42,56 OCD and BDD symptoms may remit differently. Studies have noted that BDD symptoms often improve before OCD symptoms, even though when comparing effects of BDD to those of OCD the impairment caused by BDD is usually more severe. 57,58 In cases of severe OCD without comorbid BDD, atypical antipsychotics combined with high-dose SRI treatment have demonstrated efficacy in helping curb urges to engage in compulsive behaviors. 22,59 OCD patients are usually aware of their irrational thoughts and are more willing to take medications than BDD patients who often fail to see their thoughts or behaviors as irrational. BDD patients tend to seek medical or surgical treatment concerns regarding perceived flaws in appearance. 24,27,57,58,60 For patients with comorbid OCD and BDD, combining an antipsychotic to the SRI usuall helps the OCD symp- Primary Psychiatry MBL Communications 64

5 Pharmacologic Treatment of Body Dysmorphic Disorder toms even if BDD symptoms remain refractory. 59 Larger and more definitive studies examining the effects of augmenting SRI treatments with atypical antipsychotics are needed among patients with both BDD and OCD so as to more closely explore factors affecting response to treatment with augmentation medications. 42 Eating Disorders Patients with eating disorders and BDD share preoccupations with appearance. Among patients with anorexia nervosa, which is marked by a preoccupation with weight loss, maintaining thinness is often accompanied by classic behaviors such as calorie counting; excessive exercise; use of laxatives, stimulants, or diuretics; or excessive weighing. According to the DSM-IV, if appearance preoccupations can be accounted for by another disorder, (such as an eating disorder), BDD is not diagnosed. 36 However, a fair number of patients with eating disorders have preoccupations with physical appearance apart from weight. Dissatisfaction with hair, skin, face, any part of the body, or overall body shape may be comorbid with an eating disorder. In this case, BDD is diagnosed Interestingly, a recent study interviewed inpatients hospitalized with anorexia and found that 25% had clear BDD symptoms 6 months prior to the onset of eating-disorder behavior. 61 As noted in the treatment Algorithm, patients with anorexia often fail to respond to an SRI until nutritional status has been restored. Once patients have sufficient stores of amino acids for producing neurotransmitters such as serotonin, the use of pharmacotherapy using SRIs may be of benefit. When binge-eating disorder and bulimia nervosa are comorbid with BDD, treatment with SRIs may be of benefit. Given that bulimia and binge-eating disorder patients may have problems with impulsivity, screening for a family history of bipolar disorder is important since SRI treatment for BDD could lead to a manic episode in a patient with latent bipolar disorder. If a family history of bipolar disorder exists, treatment using a mood stabilizer prior to initiating an SRI to target BDD has been clinically helpful for several patients. Medications that are weight-neutral, such as lamotrigine, would be preferable to mood stabilizers with weight-related side effects given the concerns about weight in patients with bulimia and binge-eating disorder. Though rare, the risk of developing Stevens-Johnson s syndrome during treatment with lamotrigine is a potential risk associated with this medication. Any patient treated with lamotrigine needs to be informed of the potential for developing this problem. Slow titration of lamotrigine is supposedly a means for avoiding this rash. Thus, titration of lamotrigine 25 mg/week to a target dose of 150 mg/week before the addition of SRIs (to target BDD symptoms) has been effective in clinical work with patients having comorbid BDD and binge-eating disorder. Similarly, for patients with BDD comorbid with bulimia, if impulsivity is a problem or if there is a family history of bipolar disorder, treatment with a mood stabilizer would also be worth consideration prior to adding an SRI to target BDD symptoms. If bulimic patients are vomiting on a regular basis, dehydration and electrolyte disturbances may be exacerbated by lithium and topiramate. Lamotrigine or gabapentin may be better choices of mood stabilizers for patients with BDD and comorbid bulimia. Substance Abuse Patients suffering from BDD often abuse substances for any number of reasons. It is critical that the patient stop abusing substances in order for pharmacotherapy efficacy to occur. Forming an alliance with the BDD patient and encouraging substance-abuse treatment is critical to successful treatment with an SRI. Determining the efficacy of pharmacotherapy for BDD is unlikely so long as the patient abuses substances. 19,67 Impulse-Control Disorders Clusters of symptoms such as substance abuse, impulsivity, and delusions, combined with BDD, substantially increase the risk of suicide attempts among patients. These patients, as in other comorbid disorders sharing features of impulsivity, may benefit from treatment with a mood stabilizer. Choices include gabapentin, lithium, valproate, and lamotrigine. A particularly difficult problem with features of impulsivity is skin picking. Typically, skin picking is not considered BDD. However, BDD is diagnosed if the person is excessively obsessed with skin pores, slight blemishes, or skin features, and then picks at the skin on the face. 64 Patients with BDD and skin picking are at high risk for complications such as severe infection and permanent scarring. Emotional distress and impulsive suicide attempts can result from distress related to self-inflicted skin damage. 64 Of the treatments available for skin picking, strong evidence supports the use of SRIs As in other disorders comorbid with BDD, if there is a concern of latent bipolar disorder or impulsivity, treatment with a mood stabilizer Primary Psychiatry MBL Communications 65

6 S.J. Hadley, S. Kim, L. Priday, E. Hollander prior to SRI treatment is worth consideration. Particularly in the case of BDD comorbid with skin picking, the use of a mood stabilizer may help the patient curb urges to pick at the skin, as well as dampen the emotional responses to observing self-inflicted skin damage. Body Dysmorpic Disorder and Comorbid Social Anxiety Disorder The prevalence of SAD in the United States is approximately 11% to 13%, while rates of BDD are 1%. However, among patients with SAD, the prevalence of BDD is 11%. 42 Patients with both SAD and BDD have intense fears of being judged or observed in social situations. SAD comorbid with BDD has a poor prognosis, given that the combination of problems can quickly lead to the patient becoming home bound, avoiding interactions with people, or being absent from school or work, or may result in deterioration in overall functioning. In addition to fears related to being judged or criticized, patients with SAD can develop severe physical symptoms from anxiety, including palpitations, nausea, sweating, and shortness of breath, which exacerbate avoidant behaviors. 54 SAD pharmacotherapy includes the use of gabapentin, venlafaxine, β-blockers, benzodiazepines, and SRIs. 55,68-70 With ALGORITHM BDD TREATMENT ALGORITHM Confirm BDD diagnosis Comorbid symptoms/family history of bipolar disorder No First Treatment: SRI for 12 weeks, 2 4 weeks at highest tolerated dose recommended by manufacturer Second Treatment Decision: If response If no response Yes For all comorbidities: If patient has positive history of bipolar, treat with mood stabilizer first, then add SRI, SNRI, atypical antipsychotic, buspirone, or bupropion. Delusional symptoms: Prescribe SRI for at least 12 weeks with 2 4 weeks at highest tolerated dose recommended by manufacturer. If no response, consider augmentation with buspirone or an atypical antipsychotic. Depression: + Family history of bipolar: Add a mood stabilizer such as lithium or lamotrigine. Once the patient is on a stable dose of mood stabilizer, add an SRI and increase the SRI as tolerated. - Family history of bipolar: Increase SRI and prescribe for at least 12 weeks with 2 4 weeks at highest tolerated dose recommended by manufacturer. OCD: Prescribe SRI for at least 12 weeks with 2 4 weeks at highest tolerated dose recommended by manufacturer. If there is no response, consider augmentation with buspirone, bupropion, clomipramine (check levels), an atypical antipsychotic, or a mood stabilizer. Eating disorders: Anorexia nervosa: Treat malnutrition. Once weight is stabilized, start an SRI and increase as tolerated; augment with buspirone, bupropion (If not bulimic), or a mood stabilizer Bulimia nervosa: Prescribe SRI. Titrate to highest tolerated dose recommended by manufacturer. Treat impulsivity with a mood stabilizer such as lamotrigine (If actively vomiting, check labs/ekg regularly). Do not prescribe bupropion. Binge-eating disorder: Prescribe SRI. Titrate SRI to highest tolerated dose recommended by manufacturer. Consider augmentation with a mood stabilizer (topiramate if no vomiting). Impulsivity: Prescribe SRI for at least 12 weeks with 2 4 weeks at highest tolerated dose recommended by manufacturer. If the patient does not respond, consider a mood stabilizer or an atypical antipsychotic. Skin picking: Prescribe SRI for at least 12 weeks with 2 4 weeks at highest tolerated dose recommended by manufacturer. If no response, consider a mood stabilizer. SAD: Prescribe an SRI or SNRI. Maintain. If sexual side effects occur, add bupropion or sildenafil Consider adding buspirone,bupropion, atypical antipsychotic, or clomipramine (check blood levels). If no response, consider adding CBT or switch to another SRI BDD=body dysmorphic disorder; SRI=serotonin reuptake inhibitor; CBT=cognitive-behavioral therapy; OCD=obsessive-compulsive disorder; SNRI=serotonin norepinephrine reuptake inhibitor; EKG=electrocardiogram; SAD=social anxiety disorder. Hadley SJ, Kim S, Priday L, Hollander E. Primary Psychiatry. Vol 13, No Primary Psychiatry MBL Communications 66

7 Pharmacologic Treatment of Body Dysmorphic Disorder the exception of the SRIs, treatment with these other medications are rarely effective for BDD. 42 Thus, when evaluating a patient with SAD, it is critical to question the person about appearance concerns, as overlooking BDD symptoms could lead to treatment of the person for SAD, and conceivably the choice of medication would be of little benefit to the person with comorbid BDD and SAD. APPROACHES TO TREATMENT- RESISTANT BODY DYSMORPHIC DISORDER: AUGMENT VERSUS SWITCH For a majority of BDD cases, SRI treatment leads to at least a partial improvement in symptoms. There are few controlled trials available which guide treatment when patients have a suboptimal response to SRIs. Based on clinical evidence, 1-4 the main two approaches to managing patients failing to respond to SRIs are augmenting the SRI with another psychotropic or CBT, or switching to a different SRI. Augmentation of Serotonin Reuptake Inhibitors with Different Types of Psychotropic Medications Evidence supporting augmentation of SRIs for BDD is based primarily on clinical reports. As previously discussed, the efficacy of augmenting an SRI with an antipsychotic is unclear and is in need of further study. 71,72 The benefits of augmenting SRIs with other psychotropic medications are also unclear. There are case reports of improvement following augmentation of an SRI with buspirone, 73 clonazepam, 1-3,74 clomipramine, 14,75 and CBT. 76,77 Augmentation of Serotonin Reuptake Inhibitors with Antipsychotics As noted earlier, studies examining the efficacy of antipsychotic monotherapy with atypical antipsychotics yielded mixed results, indicative of the need for more definitive trials. When patients with BDD are impulsive, have tics or Tourette s disorder, or fail to respond to SRIs, monotherapy with an antipsychotic or antipsychotic augmentation of an SRI could conceivably decrease problematic symptoms. Though earlier reports of SRI augmentation with antipsychotics were favorable, later reports were less favorable. As previously described, augmentation of fluoxetine with pimozide versus placebo for BDD did not result in significant improvement of BDD symptoms. 71 Similar open-label augmentation of fluoxetine with olanzapine for BDD did not result in significant improvement of symptoms among the group of subjects, though it should be mentioned that two of six patients did respond to olanzapine augmentation. 72 Larger controlled studies are needed to clarify the role of antipsychotics for the treatment of BDD. Augmentation of the Serotonin Reuptake Inhibitor with Tricyclic Antidepressants The tricyclic antidepressant clomipramine has both serotonergic and noradrenergic activity. As described in the Table, a double-blind cross-over trial conducted among patients with BDD demonstrated the efficacy of clomipramine over desipramine for the treatment of BDD. 14 In another retrospective review of BDD patients with only a partial response to SRIs, clomipramine augmentation of SRI treatment resulted in a 44% improvement of BDD symptoms. 1-3,78 Of note, when adding clomipramine to an SRI, the clinician should start with low doses of clomipramine; this is important because SRIs will block the metabolism of clomipramine, resulting in elevated and cardiotoxic levels of clomipramine. In general, clomipramine levels need to be checked frequently to ensure levels are not in the toxic range. Augmentation of Serotonin Reuptake Inhibitors with Anxiolytics Benzodiazepines Benzodiazepines may be helpful in managing severe anxiety or panic among BDD patients. However, as monotherapy, they are not considered effective treatments for BDD. Nonetheless, particularly in the 2 4 week interim between starting an SRI and a partial response to treatment, use of clonazepam or another benzodiazepine may be helpful. In addition, benzodiazepines are often helpful for sleep disturbances in BDD patients. 1-6 Buspirone Buspirone, a serotonin 5-HT 1A agonist often used for anxiolytic purposes, has been shown in retrospective BDD treatment reviews to improve BDD symptoms in patients failing to adequately respond to an SRI. One study reported that buspirone augmentation of an SRI led to significant improvement in symptoms for 33% of subjects who had failed to have an adequate response to the SRI monotherapy. 2 Similar findings were reported in an open-label study describing BDD improvement following augmentation of an SRI with buspirone. For this study, symptoms improved for 46% of patients with BDD who were previously refractory to SRI treatment. 73 Primary Psychiatry MBL Communications 67

8 S.J. Hadley, S. Kim, L. Priday, E. Hollander Changing the Serotonin Reuptake Inhibitor Studies comparing SRI efficacy in treatment of BDD remain to be conducted. Thus, the strategy for switching to a different SRI is basically trial and error. Though a patient fails to respond to one SRI, there is still a strong likelihood of the patient responding to a different SRI. In fact, clinical evidence has shown that several trials of an SRI may be necessary before finding an SRI that works. 1-6 CONCLUSION BDD shares symptoms similar to other psychiatric disorders such as OCD, SAD, eating disorders, and depression. These symptoms, if comorbid in patients with BDD, can contribute to misdiagnosis and ineffective or inadequate treatment. Medications which are effective for comorbidities are often ineffective for the treatment of BDD. Though there is no medication with an FDA indication for the treatment of BDD, converging clinical and research evidence supports the use of SRIs as the mainstay of treatment for BDD. SRI pharmacotherapy research in BDD, combined with studies demonstrating exacerbation of BDD symptoms following eating a diet deficient in tryptophan, lends support to the conceptualization of BDD as a disorder related to serotonin dsyregulation. 79 As discussed in the article, many questions remain to be investigated with respect to BDD neurobiology and treatment. Specifically, the role of antipsychotics in the treatment of BDD is a controversial topic and is in need of further investigation. Optimal treatment of BDD involves a multidisciplinary approach, since patients with BDD frequently lack insight into their illness and will seek medical or surgical treatment for correction of perceived slight or nonexistent flaws in appearance. Psychiatrists as well as primary care physicians, dermatologists, plastic surgeons, and other medical providers ideally need to collaborate to treat these patients. In addition, clinicians must be vigilant in asking patients about appearance concerns since the majority of patients with BDD will not disclose these symptoms unless specifically asked. Clinicians also need to recognize symptoms of BDD, distinguish BDD from other disorders sharing similar features, and understand the unique features of pharmacologic treatment of BDD which distinguish it from disorders sharing similar characteristics. PP REFERENCES 1. Phillips KA. Pharmacologic treatment of body dysmorphic disorder. Psychopharmacol Bull. 1996;32(4): Phillips KA, Albertini RS, Siniscalchi JM, Khan A, Robinson M. Effectiveness of pharmacotherapy for body dysmorphic disorder: a chart-review study. J Clin Psychiatry. 2001;62(9): Phillips KA. 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J Clin Psychiatry. 2003;64(6): Phillips KA. An open-label study of escitalopram in body dysmorphic disorder. Int Clin Psychopharmacol. 2006;21(3): Heimann SW. SSRI for body dysmorphic disorder. J Am Acad Child Adolesc Psychiatry. 1997;36(7): Grant JE, Phillips KA. Recognizing and treating body dysmorphic disorder. Ann Clin Psychiatry. 2005;17(4): Rosen JC, Reiter J, Orosan P. Cognitive-behavioral body image therapy for body dysmorphic disorder. J Consult Clin Psychol. 1995;63(2): Erratum in: J Consult Clin Psychol. 1995;63(3): Neziroglu F, Khemlani-Patel S. A review of cognitive and behavioral treatment for body dysmorphic disorder. CNS Spectr. 2002;7(6): Saxena S, Winograd A, Dunkin JJ, et al. A retrospective review of clinical characteristics and treatment response in body dysmorphic disorder versus obsessive-compulsive disorder. J Clin Psychiatry. 2001;62(1): DeMarco LM, Li LC, Phillips KA, McElroy SL. Perceived stress in body dysmorphic disorder. 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Selective serotonin reuptake inhibitor-induced sexual dysfunction: clinical and research considerations. Int Clin Psychopharmacol. 1998;13(suppl 6):S27-S Gitlin MJ, Suri R, Altshuler L, Zuckerbrow-Miller J, Fairbanks L. Bupropion-sustained release as a treatment for SSRI-induced sexual side effects. J Sex Marital Ther. 2002;28(2): Munro A. Monosymptomatic hypochondriacal psychosis. Br J Psychiatry Suppl. 1988;(2): Phillips KA. Body dysmorphic disorder: the distress of imagined ugliness. Am J Psychiatry. 1991;148(9): Carroll BJ, Yendrek R, Degroot C, Fanin H. Response of major depression with psychosis and body dysmorphic disorder to ECT. Am J Psychiatry. 1994;151(2): Phillips KA, Kim JM, Hudson JI. Body image disturbance in body dysmorphic disorder and eating disorders. Obsessions or delusions? Psychiatr Clin North Am. 1995;18(2): Zimmerman M, Mattia JI. Body dysmorphic disorder in psychiatric outpatients: recognition, prevalence, comorbidity, demographic, and clinical correlates. Compr Psychiatry. 1998;39(5): Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; Capstick N. Depressive reactions in the course of clomipramine therapy used in the treatment of obsessional conditions. Scott Med J. 1975;20(1 suppl): Vargel S, Ulusahin A. Psychopathology and body image in cosmetic surgery patients. Aesthetic Plast Surg. 2001;25(6): Nierenberg AA, Phillips KA, Petersen TJ, et al. Body dysmorphic disorder in outpatients with major depression. J Affect Disord. 2002;69(1-3): Aski R, Cilli AS. Body dysmorphic disorder in psychiatric outpatients: diagnosis, other psychiatric diagnosis, demographic and clinical correlates [Turkish]. Turk Psikiyatri Derg. 2002;13(3): Rotenberg KJ, Taylor D, Davis R. Selective mood-induced body image disparagement and enhancement effects: are they due to cognitive priming or subjective mood? Int J Eat Disord. 2004;35(3): Phillips KA, Stout RL. 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9 Pharmacologic Treatment of Body Dysmorphic Disorder 43. Winokur G, Black DW, Nasrallah A. Depressions secondary to other psychiatric disorders and medical illnesses. Am J Psychiatry. 1988;145(2): Brawman-Mintzer O, Lydiard RB, Phillips KA, et al. Body dysmorphic disorder in patients with anxiety disorders and major depression: a comorbidity study. Am J Psychiatry. 1995;152(11): McKay D, Todaro J, Neziroglu F, Campisi T, Moritz EK, Yaryura-Tobias JA. Body dysmorphic disorder: a preliminary evaluation of treatment and maintenance using exposure with response prevention. Behav Res Ther. 1997;35(1): Phillips KA, Diaz SF. Gender differences in body dysmorphic disorder. J Nerv Ment Dis. 1997;185(9): Phillips KA, Menard W, Fay C, Weisberg R. Demographic characteristics, phenomenology, comorbidity, and family history in 200 individuals with body dysmorphic disorder. Psychosomatics. 2005;46(4): Grant JE, Kim SW, Crow SJ. Prevalence and clinical features of body dysmorphic disorder in adolescent and adult psychiatric inpatients. J Clin Psychiatry. 2001;62(7): Phillips KA, McElroy SL, Hudson JI, Pope HG Jr. Body dysmorphic disorder: an obsessive-compulsive spectrum disorder, a form of affective spectrum disorder, or both? J Clin Psychiatry. 1995;56(suppl 4):41-51; discussion Phillips KA, Menard W, Pagano ME, Fay C, Stout RL. Delusional versus nondelusional body dysmorphic disorder: clinical features and course of illness. J Psychiatr Res. 2006;40(2): Elmer KB, George RM, Peterson K. Therapeutic update: use of risperidone for the treatment of monosymptomatic hypochondriacal psychosis. J Am Acad Dermatol. 2000;43(4): Weintraub E, Robinson C. A case of monosymptomatic hypochondriacal psychosis treated with olanzapine. Ann Clin Psychiatry. 2000;12(4): Chaichan W. Olanzapine plus fluvoxamine and olanzapine alone for the treatment of an acute exacerbation of schizophrenia. 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Self-injurious skin picking: clinical characteristics and comorbidity. J Clin Psychiatry. 1999;60(7): Grant JE, Menard W, Pagano ME, Fay C, Phillips KA. Substance use disorders in individuals with body dysmorphic disorder. J Clin Psychiatry. 2005;66(3): Lepola U, Koponen H, Leinonen E. Citalopram in the treatment of social phobia: a report of three cases. Pharmacopsychiatry. 1994;27(5): Kosieradzki PH. Citalopram in social phobia. J Am Acad Child Adolesc Psychiatry. 2001;40(10): Jefferson JW. Social anxiety disorder: more than just a little shyness. Prim Care Companion J Clin Psychiatry. 2001;3(1): Phillips KA. Placebo-controlled study of pimozide augmentation of fluoxetine in body dysmorphic disorder. Am J Psychiatry. 2005;162(2): Phillips KA. Olanzapine augmentation of fluoxetine in body dysmorphic disorder. Am J Psychiatry. 2005;162(5): Phillips KA. An open study of buspirone augmentation of serotonin-reuptake inhibitors in body dysmorphic disorder. 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