Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder

Am J Psychiatry. 2005 Jan;162(1):151-61. doi: 10.1176/appi.ajp.162.1.151.


Objective: The purpose of the study was to test the relative and combined efficacy of clomipramine and exposure and ritual prevention in the treatment of obsessive-compulsive disorder (OCD) in adults. Serotonin reuptake inhibitors (SRIs) and cognitive behavior therapy by exposure and ritual prevention are both established treatments for OCD, yet their relative and combined efficacy have not been demonstrated conclusively.

Method: A double-blind, randomized, placebo-controlled trial comparing exposure and ritual prevention, clomipramine, their combination (exposure and ritual prevention plus clomipramine), and pill placebo was conducted at one center expert in pharmacotherapy, another with expertise in exposure and ritual prevention, and a third with expertise in both modalities. Participants were adult outpatients (N=122 entrants) with OCD. Interventions included intensive exposure and ritual prevention for 4 weeks, followed by eight weekly maintenance sessions, and/or clomipramine administered for 12 weeks, with a maximum dose of 250 mg/day. The main outcome measures were the Yale-Brown Obsessive Compulsive Scale total score and response rates determined by the Clinical Global Impression improvement scale.

Results: At week 12, the effects of all active treatments were superior to placebo. The effect of exposure and ritual prevention did not differ from that of exposure and ritual prevention plus clomipramine, and both were superior to clomipramine only. Treated and completer response rates were, respectively, 62% and 86% for exposure and ritual prevention, 42% and 48% for clomipramine, 70% and 79% for exposure and ritual prevention plus clomipramine, and 8% and 10% for placebo.

Conclusions: Clomipramine, exposure and ritual prevention, and their combination are all efficacious treatments for OCD. Intensive exposure and ritual prevention may be superior to clomipramine and, by implication, to monotherapy with the other SRIs.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Behavior Therapy / methods*
  • Clomipramine / therapeutic use*
  • Combined Modality Therapy
  • Double-Blind Method
  • Female
  • Humans
  • Implosive Therapy / methods
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder / drug therapy
  • Obsessive-Compulsive Disorder / psychology
  • Obsessive-Compulsive Disorder / therapy*
  • Placebos
  • Software Design
  • Treatment Outcome


  • Antidepressive Agents, Tricyclic
  • Placebos
  • Clomipramine