Glutamatergic Agents as Add-On Medication for the Treatment of Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis

Objective: The aim of the present study was to review the existing literature on clinical trials with glutamatergic agents in adults with obsessive-compulsive disorder (OCD) and to perform a meta-analysis to estimate the overall effect size.

Data Sources: We searched in MEDLINE, Embase, and the Cochrane Library for eligible studies, using the following search terms: (glutamate OR glutaminergic OR glutamatergic OR NMDA OR AMPA OR kainate) AND (obsessive-compulsive disorder OR obsessive OR compulsive OR OCD). A separate search was performed for generally known glutamatergic agents. The databases were searched for articles published by May 31, 2015.

Study Selection: Eligible studies were double-blind, randomized controlled trials that tested the efficacy of add-on treatment with a glutamatergic agent in patients with OCD.

Data Extraction: Data were extracted independently by 2 reviewers. We extracted dichotomous data (number of patients with response and remission) to estimate relative risk ratios (RRs), as well as continuous data (scores in Yale-Brown Obsessive Compulsive Scale and Clinical Global Impressions-Severity of Illness and -Improvement scales), which were used to estimate standardized mean differences. Effect sizes were estimated using a random-effects model.

Results: Eight randomized controlled trials were identified. The overall ratio for response was RR = 3.71 (95% CI, 2.35-5.83; P < .001). When limited to the studies with treatment-resistant patients, the effect size remained significant (RR = 4.30; 95% CI, 2.19-8.43; P < .001). Secondary outcomes, such as the standardized mean differences for continuous data, showed the statistically significant superiority (P < .001) of glutamatergic agents over placebo. The risk of dropouts was RR = 1.18 (95% CI, 0.83-1.69; P = .361) and the risk of dropouts due to adverse effects was RR = 3.04 (95% CI, 1.57-5.89; P = .001).

Conclusions: Glutamatergic agents are effective as add-on treatment for OCD in general and especially for treatment-refractory OCD.