This proposal Attaining and Maintaining Wellness in OCD is a competing continuation of our prior collaborative R01 project, Cognitive Behavior Therapy Augmentation of Serotonin Reuptake Inhibitor Pharmacotherapy for Obsessive-Compulsive Disorder, and is one-half of a two-site study proposed by Dr. Edna Foa at the University of Pennsylvania and Dr. Helen Blair Simpson at the New York State Psychiatric Institute/Columbia University. Most OCD patients in clinical practice are on serotonin reuptake inhibitors (SRIs) for many years, but continue to have clinically significant residual symptoms. Our prior research showed that adding cognitive- behavioral therapy consisting of exposure and response prevention (EX/RP) is the best current strategy to help OCD patients on SRIs attain wellness. However, it is not known whether patients who attain wellness following EX/RP augmentation can then safely discontinue their SRI. OCD patients often remain on SRIs because of fear of relapse despite side effects that over time can compromise their quality of life and health (e.g., sexual dysfunction, sleep disturbance, weight gain). Hence, determining whether EX/RP can help OCD patients not only attain but also maintain wellness after discontinuing their SRI is an extremely important public health question. The primary aim of the proposed study is to examine whether adults with OCD (age 18-75) on SRIs who attain wellness after EX/RP augmentation can discontinue their SRI and maintain wellness over 6-month follow-up. We hypothesize that patients switched to pill placebo compared to those maintained on SRIs will have noninferior outcomes for OCD severity (Hypothesis #1), depressive symptoms (Hypothesis #2), and quality-of-life (Hypothesis #3) at 6-month follow-up. A secondary aim is to explore specific psychological (e.g., metacognitions) and biological factors (i.e., genetic polymorphisms) that have been theoretically or empirically linked to EX/RP outcomes and to test whether these factors help identify who will (or will not) benefit from this treatment strategy. We will recruit 150 OCD patients who have received an adequate SRI trial but still have clinically significant OCD symptoms. During the Preparatory Phase, they will receive up to 25 sessions of twice-weekly EX/RP. During the Study Phase (Weeks 0 to 24), patients (expected n=100) who attain wellness (using a Yale-Brown Obsessive Compulsive Scale score d 14 as a proxy) will be randomized to continue their SRI or switch to pill placebo and followed for 24 weeks. This study will fill an important gap in our knowledge: can EX/RP augmentation help OCD patients discontinue from SRIs? By exploring what moderates and mediates the effects of SRI discontinuation, we will also investigate who is likely to benefit from this treatment strategy and how it works. Our long-term goals are to provide clinicians with effective treatment strategies to help people with OCD live full and productive lives and to advance knowledge about the psychological, biological, and behavioral factors associated with attaining wellness with EX/RP augmentation and maintaining wellness without SRIs. PUBLIC HEALTH RELEVANCE: The focus of the present proposal is to examine whether cognitive-behavioral therapy consisting of exposure and response therapy (EX/RP) can help patients with obsessive compulsive disorder (OCD) discontinue from serotonin reuptake inhibitors (SRIs) and to investigate who is most likely to benefit from this treatment strategy. Ou goal is to provide clinicians with effective treatment strategies to help people with OCD live full and productive lives and to advance knowledge about the psychological and biological factors associated with attaining and maintaining wellness in OCD.