Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a meta-analysis of double-blind, randomized, placebo-controlled trials

Int J Neuropsychopharmacol. 2013 Apr;16(3):557-74. doi: 10.1017/S1461145712000740. Epub 2012 Aug 29.


Because of the high number of patients with obsessive-compulsive disorder (OCD) not responding satisfactorily to initial monotherapy with serotonin reuptake inhibitors (SRIs), the evaluation of additional treatment options is highly relevant. To examine efficacy of add-on pharmacotherapy with antipsychotics, a systematic literature search was applied to identify all double-blind, randomized, placebo-controlled trials (DB-PC-RCTs) determining the efficacy of antipsychotic augmentation of SRIs in treatment-resistant OCD. The primary outcome of the pooled meta-analytic data analysis was response to the adjunctive antipsychotic treatment measured by both the rates of participants achieving response [defined as ≥ 35% reduction in Yale-Brown Obsessive-Compulsive Scale (YBOCS)] and mean changes in YBOCS total score. Twelve DB-PC-RCTs investigating quetiapine (N = 5), risperidone (N = 3), olanzapine (N = 2), aripiprazole (N = 1) and haloperidol (N = 1) with a total of 394 subjects were included. Significantly more patients responded to augmentation with antipsychotics than with placebo [relative risk = 2.10, 95% confidence intervals (CI) 1.16-3.80]. Additionally, the mean reduction of the YBOCS total score revealed an efficacy in favour of the antipsychotic medication [standardized mean difference (SMD) = 0.54, 95% CI 0.15-0.93]. Significant efficacy was identifiable only for risperidone, but not for quetiapine and olanzapine. The results regarding aripiprazole and haloperidol were inconsistent. Overall, about one-third of SRI-resistant OCD patients benefited from an augmentation strategy with antipsychotics. Based on the favourable risk:benefit ratio, risperidone can be considered as the agent of first choice and should be preferred to quetiapine and olanzapine. Further trials, mainly with higher antipsychotic doses, are required to optimize pharmacological treatment recommendations for SRI-refractory OCD.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Antipsychotic Agents / administration & dosage*
  • Double-Blind Method
  • Drug Resistance / drug effects
  • Drug Resistance / physiology
  • Drug Synergism
  • Drug Therapy, Combination
  • Humans
  • Obsessive-Compulsive Disorder / drug therapy*
  • Obsessive-Compulsive Disorder / epidemiology
  • Obsessive-Compulsive Disorder / psychology
  • Randomized Controlled Trials as Topic
  • Selective Serotonin Reuptake Inhibitors / administration & dosage*
  • Treatment Outcome


  • Antipsychotic Agents
  • Serotonin Uptake Inhibitors