Memantine Augmentation of Sertraline in Severity of Symptoms and Cognitive Function Among Patients with Obsessive-Compulsive Disorder: A Double-Blind Placebo-Controlled, Randomized Clinical Trial

Abstract Background: Medications currently recommended for the treatment of Obsessive-Compulsive Disorder (OCD) usually decrease the severity of the symptoms by 20–30%, and 40–60% of OCD patients do not achieve satisfactory treatment. In this study, the main objective was to investigate the effectiveness of memantine, which is a non-competitive N-Methyl-D-aspartate (NMDA) receptor antagonist, as an adjunct therapy to sertraline, a selective serotonin reuptake inhibitor (SSRI), to improve severity of symptoms and cognitive function among patients with obsessive-compulsive disorder. Methods: 70 patients who based on Diagnostic and Statistical Manual of Mental Disorders (DSM–5) criteria were diagnosed with OCD, and had a Yale-Brown obsessive compulsive scale (Y-BOCS) score of more than 21, were recruited in a placebo controlled, double-blinded, parallel-group, clinical trial of 12 weeks to receive either memantine (10 mg twice daily) and sertraline (100 mg daily initially followed by 200 mg daily after week 4) or placebo and sertraline. The primary outcome was OCD symptoms measured by the Y-BOCS, moreover, the executive function and the cognition of participants was measured by the Wisconsin Card Sorting Test (WCST).Results: Y-BOCS score in total, obsession and compulsion subscales significantly dropped in both groups; however, there was not a significant difference between them. In comparison of cognition, memantine group showed a greater response in number of categories subscale in the WCST (p value<0.001). No major adverse effects were observed in any of the groups. Conclusion: Our findings suggest a probable effect of memantine as adjuvant therapy to sertraline on cognitive function of patients with OCD as well as its safety and tolerability in comparison with placebo. Nevertheless, the current results don`t support the efficacy of memantine as an adjunctive agent to sertraline for improving severity of symptoms among patients with OCD.Trial registration: The trial was registered at the Iranian Registry of Clinical Trials on 2019-10-04 (www.irct.ir; IRCT ID: IRCT20170123032145N4).