Effect of memantine combination therapy on symptoms in patients with moderate-to-severe depressive disorder: randomized, double-blind, placebo-controlled study

What is known and objectiveCurrent treatments for depressive disorders are far from optimum. This study was planned to evaluate possible antidepressant effects and safety of memantine, a selective N-methyl-d-aspartate receptor antagonist, in humans. MethodsSixty-six outpatients with the diagnosis of moderate-to-severe major depressive disorder, based on DSM-V diagnostic criteria, were recruited to participate in a parallel, randomized, controlled trial. Sixty-two participants completed 6weeks of treatment with either memantine (20mg/day) plus sertraline (200mg/day) or placebo plus sertraline (200mg/day). Patients were evaluated using the Hamilton Depression Rating Scale (HDRS) at baseline and at weeks 2, 4 and 6. Comparison of treatment efficacy in improving depressive symptoms between the two groups was the principal outcome measure. Results and discussionA repeated-measures analysis demonstrated significant timextreatment interaction on HDRS score [F (209, 12567)=509, P=0007]. Significantly greater improvement was seen at all three follow-up sessions as well as significantly greater response rates at weeks 4 and 6 (P=0018 and P<0001, respectively) in the memantine group. Significantly more early improvers and more rapid response to treatment were observed in the memantine group (P=0001 and P<0001, respectively). A significant reduction was observed in HDRS score from baseline to the study endpoint in both memantine (P<0001, Cohen's d=1271) and placebo groups (P<0001, Cohen's d=513). No serious adverse event occurred. No significantly greater remission rate was seen in the adjunctive memantine therapy. What is new and conclusionA 6-week course of treatment with memantine as adjunct to sertraline showed a favourable safety and efficacy profile in patients with major depressive disorder. Nonetheless, larger controlled studies of longer duration are necessary to assess long-term safety, efficacy and optimal dosing.