Obsessive-compulsive disorder (OCD) affects 2% to 3% of adults worldwide. Although serotonin reuptake inhibitors (SRIs) reliably demonstrate efficacy for this condition, 40% to 60% of patients only achieve partial recovery. The purpose of this systematic review was to assess the efficacy of other agents that may be used as augmentation agents for patients who are partial responders to SRI monotherapy.

Using PRISMA-P guidelines, PubMed and Embase were searched using the randomized controlled trial (RCT) filter and the key word “obsessive-compulsive disorder.” To be considered for analysis, a potential augmentation agent needed to have at least 2 RCTs. This review specifically analyzes the effect of each augmentation agent on OCD symptoms as measured by the Yale-Brown Obsessive-Compulsive Scale.

The augmentation agents analyzed in this review are d-cycloserine (2 RCTs), memantine (4 RCTs), N-acetylcysteine (5 RCTs), lamotrigine (2 RCTs), topiramate (3 RCTs), riluzole (2 RCTs), ondansetron (2 RCTs), celecoxib (2 RCTs), aripiprazole (5 RCTs), risperidone (7 RCTs), quetiapine (9 RCTs), and olanzapine (3 RCTs).

The augmentation agents most supported by this review for OCD that is only a partial response to SRI monotherapy are lamotrigine, memantine, and aripiprazole. If an antipsychotic must be used and aripiprazole is not tolerated, risperidone may be considered as an alternative. Unlike the SRI class effect for OCD symptom reduction, augmentation agents demonstrate considerable intraclass variability.