Augmentation With Memantine in Obsessive-Compulsive Disorder.

Abstract

Patients with obsessive-compulsive disorder (OCD) who do not respond adequately to serotonin reuptake inhibitor (SRI) therapy and cognitive behavioral therapy commonly receive SRI augmentation in the form of an atypical antipsychotic drug. Memantine is another augmentation strategy that has been trialed. A recent systematic review and meta-analysis found very large improvements associated with memantine augmentation in OCD. Specifically, in 4 randomized controlled trials (RCTs), the response rate was 81% in 67 memantine-treated patients vs only 19% in 68 placebo-treated patients. The weighted mean difference between memantine and placebo groups was nearly 8 points on the Yale-Brown Obsessive Compulsive Scale. Such striking differences for intervention vs placebo in a difficult-to-treat disorder demand scrutiny. An examination of the RCTs on which the meta-analysis was based showed that all 4 RCTs emerged from the same geographical area, limiting the generalizability of the findings. Of greater concern, all 4 RCTs presented what were effectively completer analyses of data, compromising the scientific validity of the findings. There were several other concerns about the individual studies and about the meta-analysis, itself. Therefore, a reasonable conclusion is that, when the internal and external validity of studies in a meta-analysis are compromised, the findings and conclusions of the meta-analysis cannot be considered sound. It is concluded that, despite the very large benefits reportedly associated with memantine augmentation, the routine use of memantine as an augmentation agent for OCD cannot as yet be recommended.