Sabine Wilhelm - US grants

Obsessive-Compulsive Disorder (OCD) is a prevalent and often chronic disorder that is currently treated with pharmacological and psychological approaches. Exposure combined with response prevention (ERP) is presently considered the psychological treatment of choice. However, many patients refuse, drop out of or are unresponsive to pharmacotherapy or ERP. Many patients never engage in treatment or experience significant impairment even after treatment. Further, ERP may be less acceptable to therapists and to managed care settings. Thus, additional interventions for the treatment of OCD that improve outcome are needed. Recent studies suggest that cognitive treatment (CT) for OCD is at least as effective as exposure and response prevention. Moreover, cognitive approaches may be less stressful and have lower refusal rates than intensive forms of exposure or pharmacotherapy. CT also appears to help patients with symptoms that do not benefit from standard treatment. Finally, CT may be more acceptable to therapists and health care settings. This proposal seeks funds to develop, systemize and pilot test a cognitive treatment for patients suffering from OCD based mainly on Beck's methods. This treatment is derived from a theoretical model of cognitive aspects and effects on OCD symptoms and from empirical evidence regarding interpretation of intrusions and beliefs found in patients with OCD. We propose to fully develop a treatment manual, and accompanying therapist adherence and competency measures. After the treatment development phase, we will apply cognitive therapy of three different durations to OCD patients to determine which format is clinically most useful. In the final phase, we will collect pilot data on the best version of the therapy in comparison to a wait-list control. We will investigate treatment effects on different cognitive domains, specific OCD symptoms, mood state and functioning. The effect size of cognitive therapy for a primary outcome variable, the Yale-Brown Obsessive Compulsive Scale and response rate of treated subjects will be determined, preparatory to a larger scale randomized controlled trial, if this is indicated. Using a combined sample of 30 patients we will study the influence of a small number of possible predictors of posttest outcome.

DESCRIPTION (provided by applicant): Body dysmorphic disorder (BDD), a preoccupation with an imagined or slight defect in appearance, is a distressing, impairing, and under recognized disorder that is relatively common. It is a severe body image disorder that is associated with serious social and occupational impairment, high rates of hospitalization and suicide attempts, notably poor quality of life, and completed suicide. Although BDD is a significant public health problem, little research on its treatment has been done. While pharmacotherapy appears effective for BDD, a significant proportion of patients refuse, or are unresponsive to this treatment. Thus, it is critically important to develop effective psychological interventions. Recent studies suggest that cognitive behavioral therapy (CBT) is a promising treatment for BDD, but few CBT efficacy studies have been done, and a widely applicable CBT treatment manual is not available. This treatment development application proposes to develop, systemize, and pilot test a cognitive behavioral treatment for patients with BDD. The research team proposes to fully develop a treatment manual and accompanying therapist adherence and competence measures. Thereafter, CBT of 3 different durations will be openly applied by the treatment developers to BDD patients to determine which duration is clinically most useful and to revise the manual. In the study's final phase, the CBT treatment will be pilot tested using a waitlist control condition (n=36). Treatment effects on BDD symptoms, mood, functioning, quality of life, and other domains will be investigated, and possible predictors of treatment outcome will be explored. The resulting effect size will determine whether larger-scale randomized controlled trials of CBT for BDD are indicated. In summary, because there are no well-established psychosocial treatments for BDD, the proposed work will address an important gap in our knowledge and a pressing public health need, and it will lay essential groundwork for future, more definitive intervention studies for this common, severe, and understudied body image disorder.

DESCRIPTION (provided by applicant): Tourette Syndrome (TS) is a neurological disorder characterized by persistent motor and vocal tics. Tics can be brief, rapid and darting movements of the face, shoulders, and extremities or more complex and purposeful in appearance. Vocal tics can be simple sounds such as sniffing or grunting or more complex sounds including repeated words and phrases. Tics wax and wane over time with peak severity between ages 10 and 12 years. However, some individuals have a more enduring course of tics into adulthood. When present in adults, the tics of TS can be associated with considerable distress, social and occupational impairment, and discrimination. A substantial body of evidence implicates dysfunction of cortical-subcortical pathways involving the thalamus, basal ganglia and the frontal cortex. Although neurologically-based, behavioral and environmental factors may also play a role in tic maintenance. Currently, the standard treatment for tic suppression is medication, particularly centrally acting dopamine-blocking drugs. However, these medications are associated with a range of adverse effects that can result in poor compliance or in premature termination of treatment. Moreover, currently available medications rarely eliminate all tics. Thus, when managing their chronic condition, adults are often faced with a partial response to medication, or they opt to avoid all medications due to unacceptable side effects. Preliminary research by the investigators listed on this application suggests that a behavioral treatment called habit reversal training (HRT) is a promising intervention for tics. HRT is a multi-component treatment approach that includes awareness training, selfmonitoring, contingency management, inconvenience review, relaxation training and competing responses. HRT is designed as a monotherapy and/or as an augmentation to pharmacotherapy. Although the initial studies evaluating the efficacy of HRT in TS have been encouraging, to date the investigations have been case studies or small randomized trials, and HRT has never been systematically investigated as an augmentation to pharmacotherapy. In response to Program Announcement PA 01-123, this application describes a multisite investigation to evaluate the efficacy of a structured HRT program for tic reduction in adults with TS. To conduct this study, the Tourette Syndrome Association (TSA) assembled the Behavioral Sciences Consortium (BSC). The BSC is a multidisciplinary group of investigators representing some of the leading TS research programs in the country including Yale, Massachusetts General Hospital (MGH)/Harvard Medical School, University of California at Los Angeles (UCLA), and Johns Hopkins. Two additional centers, Wilford Hall Medical Center/University of Texas Health Sciences Center at San Antonio (WHMC/UTHSCSA), and the University of Wisconsin-Milwaukee (UWM), have investigators with specific expertise in HRT. The mission of the BSC is to develop, test, and disseminate behavioral interventions for patients with TS. In this proposed study, 120 eligible participants will be randomly assigned to receive either HRT or Enhanced- Supportive Psychotherapy. Both treatments will consist of 10 sessions over 12 weeks followed by 2 booster sessions and 3- and 6-months follow up assessments. The primary outcome of interest will be change in tic severity assessed by an independent evaluator blind to treatment assignment. The effect of HRT as a monotherapy for tics and as augmentation to ongoing, stable tic-suppressing medication will also be evaluated. The three study recruitment sites are MGH/Harvard, WHMC/UTHSCSA, and Yale University. Investigators from UCLA and the UWM will provide specific quality assurance and assessment services via separate subcontracts, and a Data Safety and Monitoring Board (DSMB) will be assembled for data and safety monitoring purposes. The Informatics group at Yale University will provide data management services.

DESCRIPTION (provided by applicant): We propose to conduct the first pharmacotherapy relapse prevention study in body dysmorphic disorder (BDD). BDD, an often-delusional preoccupation with an imagined or slight defect in appearance, is a distressing, impairing, and relatively common body image disorder. It is associated with high rates of functional impairment and markedly poor quality of life. It appears that SRIs are often--and selectively--efficacious for BDD and that many BDD patients receive SRIs. It also appears that most patients discontinue an efficacious SSRI at some point, as the alternative is life-long treatment. However, no relapse prevention studies have been done. Such a study is important from a clinical and public health perspective, because BDD appears to often be chronic and require long-term treatment. It is therefore critically important to investigate the risk of relapse with SSRI discontinuation, and whether continuation SSRI treatment decreases relapse risk. 128 subjects will be enrolled and first treated openly for 14 weeks with escitalopram; 58 escitalopram responders will then be randomized to double-blind continuation treatment with escitalopram or placebo for 6 additional months. Our primary aim is to compare time to relapse and relapse rates in responders to acute escitalopram who are then randomized to placebo versus continuation treatment with escitalopram. Secondary/exploratory aims will explore 1) Whether subjects who receive continuation escitalopram perform better on secondary outcome measures (e.g., quality of life) than those on placebo; 2) Whether subjects taking continuation escitalopram have further improvement in BDD symptoms during the continuation phase; 3) Predictors of relapse after escitalopram discontinuation; and 4) Acute treatment response. Because this study will offer a unique opportunity to investigate the genetic basis of BDD, we will explore BDD's genetic basis and the relationship of selected candidate genes to treatment outcome and side effects. In summary, this study will be the first relapse prevention study in BDD and the first study of continuation pharmacotherapy in BDD. It will provide critically important information on relapse with continuation versus discontinuation of an SRI, whether continuation treatment protects against relapse, and whether patients further improve with continuation treatment. It will explore previously unstudied questions about BDD's pharmacogenetics, which may ultimately guide and enhance medication treatment. This study will yield unique and clinically important data, and will fill gaps in knowledge about this relatively common, severe, and understudied illness.

DESCRIPTION (provided by applicant): We propose to conduct the first pharmacotherapy relapse prevention study in body dysmorphic disorder (BDD). BDD, an often-delusional preoccupation with an imagined or slight defect in appearance, is a distressing, impairing, and relatively common body image disorder. It is associated with high rates of functional impairment and markedly poor quality of life. It appears that SRIs are often--and selectively--efficacious for BDD and that many BDD patients receive SRIs. It also appears that most patients discontinue an efficacious SSRI at some point, as the alternative is life-long treatment. However, no relapse prevention studies have been done. Such a study is important from a clinical and public health perspective, because BDD appears to often be chronic and require long-term treatment. It is therefore critically important to investigate the risk of relapse with SSRI discontinuation, and whether continuation SSRI treatment decreases relapse risk. 128 subjects will be enrolled and first treated openly for 14 weeks with escitalopram;58 escitalopram responders will then be randomized to double-blind continuation treatment with escitalopram or placebo for 6 additional months. Our primary aim is to compare time to relapse and relapse rates in responders to acute escitalopram who are then randomized to placebo versus continuation treatment with escitalopram. Secondary/exploratory aims will explore 1) Whether subjects who receive continuation escitalopram perform better on secondary outcome measures (e.g., quality of life) than those on placebo;2) Whether subjects taking continuation escitalopram have further improvement in BDD symptoms during the continuation phase;3) Predictors of relapse after escitalopram discontinuation;and 4) Acute treatment response. Because this study will offer a unique opportunity to investigate the genetic basis of BDD, we will explore BDD's genetic basis and the relationship of selected candidate genes to treatment outcome and side effects. In summary, this study will be the first relapse prevention study in BDD and the first study of continuation pharmacotherapy in BDD. It will provide critically important information on relapse with continuation versus discontinuation of an SRI, whether continuation treatment protects against relapse, and whether patients further improve with continuation treatment. It will explore previously unstudied questions about BDD's pharmacogenetics, which may ultimately guide and enhance medication treatment. This study will yield unique and clinically important data, and will fill gaps in knowledge about this relatively common, severe, and understudied illness.

DESCRIPTION (provided by applicant): Body dysmorphic disorder (BDD) is a severe, often chronic, and common disorder consisting of distressing or impairing preoccupation with imagined or slight defects in appearance. Individuals with BDD have very poor functioning and high rates of hospitalization and suicidality. The rate of completed suicide, while preliminary, appears markedly high. A majority of patients receive surgical, dermatologic, or dental treatment for BDD, which is usually ineffective. Our prior work has shown that SRIs are often efficacious for BDD, but patients may not agree to try medication or may not benefit from it. Thus, there is a critical need for an efficacious psychosocial intervention for this severe disorder. Because BDD differs in important ways from other disorders, psychotherapies for other disorders are not adequate for BDD. There is no adequately tested psychosocial treatment of any type for BDD. An evidence-based treatment for this unique disorder is greatly needed. Cognitive-behavioral therapy (CBT) is the only psychosocial treatment for BDD that is fully developed and now ready for formal testing. Data from case series and studies using waitlist controls suggest that BDD- specific CBT is very promising for BDD. With an R34 grant, we developed a personalized, modular, manualized CBT treatment (CBT-BDD) that specifically targets BDD's unique and complex symptoms. The R34 study, which used a waitlist control group, suggests CBT-BDD is acceptable to patients, feasible to implement, and appears efficacious for BDD, associated symptoms, and functional disability. However, no study has adequately tested CBT's efficacy for BDD -- for example, by comparing it to another treatment that controls for therapist time, attention, and other non-specific treatment elements. Thus, there is a pressing clinical and public health need to test the most promising psychosocial treatment for BDD. This Collaborative R01 application's primary aim is to conduct the first study to adequately examine the efficacy of CBT for BDD. This study will compare our personalized and manualized CBT-BDD to manualized supportive psychotherapy (SPT). SPT appears to be the psychosocial treatment most often used for BDD, yet it appears to have a low response rate. Massachusetts General Hospital/Harvard Medical School and Rhode Island Hospital/Brown University will randomize 120 adults to CBT-BDD or SPT over 24 weeks followed by 3- and 6-month follow-up assessments. The primary outcome will be change in BDD severity assessed by a blinded Independent Evaluator. Secondary aims will examine change in depressive symptoms, delusionality of BDD beliefs, psychosocial functioning, and quality of life, as well as predictors of improvement in BDD. The United Kingdom's National Health Service treatment practice guideline on BDD and a Cochrane Collaboration review on BDD underscore the dearth of treatment research and call for more intervention research on BDD. The proposed study will fill a major gap in knowledge and patient care by conducting the first adequate test of any psychosocial treatment for a unique, disabling, common, and understudied disorder.