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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH045802-07
Application #
2890417
Study Section
Treatment Assessment Review Committee (TA)
Program Officer
Rudorfer, Matthew V
Project Start
1992-09-15
Project End
2001-04-30
Budget Start
1999-06-01
Budget End
2001-04-30
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Florida
Department
Psychiatry
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Storch, Eric A; Murphy, Tanya K; Fernandez, Melanie et al. (2007) Factor-analytic study of the Yale Global Tic Severity Scale. Psychiatry Res 149:231-7
Storch, Eric A; Bagner, Daniel; Merlo, Lisa J et al. (2007) Florida Obsessive-Compulsive Inventory: development, reliability, and validity. J Clin Psychol 63:851-9
Husted, David S; Shapira, Nathan A; Murphy, Tanya K et al. (2007) Effect of comorbid tics on a clinically meaningful response to 8-week open-label trial of fluoxetine in obsessive compulsive disorder. J Psychiatr Res 41:332-7
Storch, Eric A; Murphy, Tanya K; Adkins, Jennifer W et al. (2006) The children's Yale-Brown obsessive-compulsive scale: psychometric properties of child- and parent-report formats. J Anxiety Disord 20:1055-70
Storch, Eric A; Shapira, Nathan Andrew; Dimoulas, Eleni et al. (2005) Yale-Brown Obsessive Compulsive Scale: the dimensional structure revisited. Depress Anxiety 22:28-35
Storch, Eric A; Murphy, Tanya K; Geffken, Gary R et al. (2005) Factor analytic study of the Children's Yale-Brown Obsessive-Compulsive Scale. J Clin Child Adolesc Psychol 34:312-9
Storch, Eric A; Murphy, Tanya K; Geffken, Gary R et al. (2005) Reliability and validity of the Yale Global Tic Severity Scale. Psychol Assess 17:486-91
Storch, Eric A; Murphy, Tanya K; Geffken, Gary R et al. (2004) Psychometric evaluation of the Children's Yale-Brown Obsessive-Compulsive Scale. Psychiatry Res 129:91-8
Shapira, Nathan A; Ward, Herbert E; Mandoki, Miguel et al. (2004) A double-blind, placebo-controlled trial of olanzapine addition in fluoxetine-refractory obsessive-compulsive disorder. Biol Psychiatry 55:553-5
Storch, Eric A; Murphy, Tanya K; Geffken, Gary R et al. (2004) Further psychometric properties of the Tourette's Disorder Scale-Parent Rated version (TODS-PR). Child Psychiatry Hum Dev 35:107-20

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