Amantadine Augmentation Therapy for Obsessive Compulsive Patients Resistant to SSRIs-An Open-Label Study

Background: It has been hypothesized that glutamatergic dysfunction may play a role in the development of obsessive compulsive disorder (OCD) and that glutamatergic modulation may ameliorate some of the OC symptoms. We evaluated the effectiveness of amantadine (AMN)-aweak, noncompetitive, antagonist of the N-methyl-D-aspartic acid (NMDA) receptor-as an adjunctive therapy to selective serotonin reuptake inhibitors (SSRIs), and its role in improving OC symptoms in cases refractory to SSRI pharmacotherapy alone. Methods: Eight patients (5males and 3 females, aged 42.6 +/- 13.1 years) that met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for OCD, scored above 20 points on Yale Brown Obsessive Compulsive Scale (Y-BOCS) and were unresponsive to at least one SSRI, completed an open label study of 6 weeks duration. AMN was added to the current stable SSRI regimen and baseline and endpoint changes in Y-BOCS, depression and anxiety levels were analyzed. Results: Significant reductions in total Y-BOCS (28 +/- 4.5 vs. 18.8 +/- 8.8; P < 0.01; df = 7; t = 2.36), Y-BOCS compulsion sub-scale (15.3 +/- 3.2 vs. 10.6 +/- 4.7; P < 0.02; df = 7; t = 2.36), and Y-BOCS obsession sub-scale (12.7 +/- 3.3 vs. 8.1 +/- 5; P < 0.05; df = 7; t = 2.36) scores were obtained at endpoint. The anxiety and depression levels remained unaltered. Conclusions: AMN adjunction to SSRI treatment may lead to a significant reduction in OC symptoms, supporting the hypothesis that transduction of the glutamate signal via NMDA receptor may play a role in OCD. A large scale, double-blind, placebo-controlled study is warranted to confirm our results.