Obsessive Compulsive Disorder (OCD) is a common, often chronic, and sometimes disabling neuropsychiatric condition. The hypothesis that a disturbance in serotonin function is related to the etiology of OCD is based primarily on the anti-obsessive-compulsive (OC) efficacy of potent serotonin reuptake inhibitors (SRIs) such as fluvoxamine. Although SRIs are an advance in the treatment of OCD, many patients fail to respond and few become asymptomatic. Underlying biological heterogeneity may help explain this variable treatment response. Multiple lines of evidence suggest a meaningful relationship between some forms of OCD and Tourette's Syndrome (TS). That classic neuroleptics such as haloperidol can suppress tics provides indirect support for a role of brain dopamine in the pathophysiology of TS. The presence of a comorbid tic disorder seems to predict a poor response of OC symptoms to SRI monotherapy. It has been shown, however, that OCD patients with a comorbid tic disorder who have not responded satisfactorily to fluvoxamine alone improved significantly when the dopamine antagonist haloperidol was added. These findings suggest that adequate control of OC symptoms in OCD patients with tics requires dual pharmacological manipulations of the serotonin and dopamine neuronal systems. Although these treatment data have important theoretical and clinical implications, the problematic acute and long-term side effects of haloperidol limit its use. Recent reports in TS patients suggest that the serotonin/ dopamine antagonist risperidone may help control tics; it is less clear whether it reduces OC symptoms when given alone. In a preliminary report of OCD patients, risperidone markedly improved OC symptoms when added to an SRI. The-research strategy guiding this project is to advance the neurobiology and treatment of OCD by focusing on TS-spectrum OCD as a more homogeneous form of OCD. In the proposed study, approximately 100 patients will be divided into TS-spectrum and NonTS-spectrum OCD based on personal and family history of tics and entered in a 12-week single-blind trial with fluvoxarnine. Those with an incomplete response to fluvoxamine alone (-N=65) will be randomized to an 6-week double-blind trial of fluvoxamine in combination with risperidone or placebo. It is predicted that the TS-spectrum OCD subgroup will respond preferentially to risperidone addition.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Treatment Assessment Review Committee (TA)
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Rudorfer, Matthew V
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University of Florida
Schools of Medicine
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