Treatment of Obsessive-Compulsive Disorder

Neurobiology/Treatment of Obsessive-Compulsive Disorder

The purpose of this study is to find the best treatment for Tourette's Syndrome (TS)-spectrum obsessive-compulsive disorder (OCD), which includes symptoms of TS, e.g., repeated and involuntary body movements (tics).

There are 2 parts to this study: In Part 1, patients are placed into 1 of 2 groups based on type of OCD, determined by medical history and family member interviews. In Part 2, patients are treated with fluvoxamine (FVX) for 8 weeks. If patients do not respond to FVX alone, either haloperidol or an inactive placebo will be added to the FVX regimen; patients will take this drug combination for 4 weeks. Patients will be monitored throughout the trial.

Study Overview

• Status: Completed
• Conditions: Obsessive-Compulsive Disorder
• Intervention / Treatment: Drug: placebo + fluoxetine; Drug: olanzapine + fluoxetine

Detailed Description

To advance the neurobiology and treatment of obsessive-compulsive disorder (OCD) by focusing on Tourette's Syndrome (TS)-spectrum OCD as a possible homogeneous form of OCD, and investigating the relevance of intact 5-hydroxytryptamine (5-HT) function to the mechanism of anti-OC drug action. The validity of TS-spectrum OCD as a distinct subtype is assessed using a detailed clinical, family, drug treatment response profile in adult OCD patients.

In Study I, patients are divided prospectively into 2 putative subtypes (TS-spectrum and non-TS-spectrum OCD) on the basis of clinical history and direct, structured interviews of family members (approximately 400 interviews).

In Study II, patients enter an 8-week single-blind trial with the potent and selective 5-HT reuptake inhibitor fluoxetine (FX). Patients with an incomplete response to FX alone (approximately 64 patients) are randomized to a 4-week double-blind trial of FX in combination with the dopamine (DA) 2 antagonist olanzapine (OLA) or placebo (PLA).

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • Psychiatric Specialty Clinic, Shands Hospital at the University of Florida
    • Jacksonville, Florida, United States, 32257
      • University of Florida Behavioral Health Mandarin Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 68 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria required that subjects, ages 14-70 years, have at least a 1-year duration of a current Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) principal diagnosis of OCD. Furthermore, the OCD had to be defined by a rating of "moderate" or greater on the global severity item of the Clinical Global Impressions (CGI) scale and have a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of 19 or greater.

Exclusion criteria included primary depression, schizophrenia, or other psychotic disorders; active bipolar disorder; abuse of alcohol or other significant substance within 6 months; increased risk of seizures or history of neurosurgery, encephalitis, or significant head trauma; or a significant medical condition, such as heart, liver, or renal disease. Subjects with an intelligence quotient of less than 80 as determined with the Kaufman Brief Intelligence Test (Kaufman and Kaufman 1990) were excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: olanzapine + fluoxetine; The specific aim was to determine whether combined treatment with fluoxetine plus olanzapine would be more effective than fluoxetine plus placebo in treating OCD subjects who were partial or nonresponders to a prospective, 8-week, open-label trial of fluoxetine.	Drug: placebo + fluoxetine
Placebo Comparator: placebo + fluoxetine; The specific aim was to determine whether combined treatment with fluoxetine plus olanzapine would be more effective than fluoxetine plus placebo in treating OCD subjects who were partial or nonresponders to a prospective, 8-week, open-label trial of fluoxetine.	Drug: olanzapine + fluoxetine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
25% reduction in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score from baseline	Baseline, Week s 1, 2, 4, 6, 8, 10, 12, and 14

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Wayne Goodman, MD, University of Florida

Publications and helpful links

General Publications

• Shapira NA, Ward HE, Mandoki M, Murphy TK, Yang MC, Blier P, Goodman WK. A double-blind, placebo-controlled trial of olanzapine addition in fluoxetine-refractory obsessive-compulsive disorder. Biol Psychiatry. 2004 Mar 1;55(5):553-5. doi: 10.1016/j.biopsych.2003.11.010.
• Koran LM, Bromberg D, Hornfeldt CS, Shepski JC, Wang S, Hollander E. Extended-release fluvoxamine and improvements in quality of life in patients with obsessive-compulsive disorder. Compr Psychiatry. 2010 Jul-Aug;51(4):373-9. doi: 10.1016/j.comppsych.2009.10.001. Epub 2009 Dec 21.

Study record dates

Study Major Dates

• Study Start: September 1, 1992
• Primary Completion (Actual): January 1, 2003
• Study Completion (Actual): July 1, 2003

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: November 2, 1999
• First Posted (Estimate): November 3, 1999

Study Record Updates

• Last Update Posted (Estimate): November 27, 2013
• Last Update Submitted That Met QC Criteria: November 26, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Adult; Placebos; Female; Human; Male; Adolescence; Antipsychotic Agents; Tourette Syndrome; Obsessive-Compulsive Disorder; Haloperidol; Fluvoxamine; Serotonin Uptake Inhibitors; Drug Combinations; Dopamine Antagonists; Middle Age; Tryptophan; Antipsychotic Agents -- *therapeutic use; Fluvoxamine -- *therapeutic use; Haloperidol -- *therapeutic use; Obsessive-Compulsive Disorder -- *drug therapy; Obsessive-Compulsive Disorder -- physiopathology; Serotonin Uptake Inhibitors -- *therapeutic use
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Personality Disorders; Anxiety Disorders; Disease; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Olanzapine; Fluoxetine
• Other Study ID Numbers: R01MH045802 (U.S. NIH Grant/Contract)