A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder

Arch Gen Psychiatry. 2000 Aug;57(8):794-801. doi: 10.1001/archpsyc.57.8.794.


Background: To date, only 1 controlled study has found a drug (haloperidol) to be efficacious in augmenting response in patients with obsessive-compulsive disorder (OCD) refractory to serotonin reuptake inhibitor (SRI) monotherapy; patients with comorbid chronic tic disorders showed a preferential response. This report describes the first controlled study of risperidone addition in patients with OCD refractory to treatment with SRI alone.

Methods: Seventy adult patients with a primary DSM-IV diagnosis of OCD received 12 weeks of treatment with an SRI. Thirty-six patients were refractory to the SRI and were randomized in a double-blind manner to 6 weeks of risperidone (n = 20) or placebo (n = 16) addition. Behavioral ratings, including the Yale-Brown Obsessive Compulsive Scale, were obtained at baseline and throughout the trial. Placebo-treated patients subsequently received an identical open-label trial of risperidone addition.

Results: For study completers, 9 (50%) of 18 risperidone-treated patients were responders (mean daily dose, 2.2 +/-0.7 mg/d) compared with 0 of 15 in the placebo addition group (P<. 005). Seven (50%) of 14 patients who received open-label risperidone addition responded. Risperidone addition was superior to placebo in reducing OCD (P<.001), depressive (P<.001), and anxiety (P =.003) symptoms. There was no difference in response between OCD patients with and without comorbid diagnoses of chronic tic disorder or schizotypal personalty disorder. Other than mild, transient sedation, risperidone was well tolerated.

Conclusion: These results suggest that OCD patients with and without comorbid chronic tic disorders or schizotypal personality disorder may respond to the addition of low-dose risperidone to ongoing SRI therapy.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use*
  • Comorbidity
  • Dopamine Antagonists / therapeutic use
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder / drug therapy*
  • Obsessive-Compulsive Disorder / epidemiology
  • Obsessive-Compulsive Disorder / psychology
  • Placebos
  • Risperidone / administration & dosage
  • Risperidone / therapeutic use*
  • Schizotypal Personality Disorder / drug therapy
  • Schizotypal Personality Disorder / epidemiology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Serotonin Antagonists / therapeutic use
  • Tics / drug therapy
  • Tics / epidemiology
  • Treatment Outcome


  • Antipsychotic Agents
  • Dopamine Antagonists
  • Placebos
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Risperidone