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


METHODS
Sixty-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 6 weeks of treatment with either memantine (20 mg/day) plus sertraline (200 mg/day) or placebo plus sertraline (200 mg/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.


CONCLUSIONS
A repeated-measures analysis demonstrated significant time × treatment interaction on HDRS score [F (2·09, 125·67) = 5·09, P = 0·007]. Significantly greater improvement was seen at all three follow-up sessions as well as significantly greater response rates at weeks 4 and 6 (P = 0·018 and P < 0·001, respectively) in the memantine group. Significantly more early improvers and more rapid response to treatment were observed in the memantine group (P = 0·001 and P < 0·001, respectively). A significant reduction was observed in HDRS score from baseline to the study endpoint in both memantine (P < 0·001, Cohen's d = 12·71) and placebo groups (P < 0·001, Cohen's d = 5·13). No serious adverse event occurred. No significantly greater remission rate was seen in the adjunctive memantine therapy.


CONCLUSIONS
A 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.
Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
M
M
Amidfar
Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
M
M
Khiabany
Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
A
A
Kohi
Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
E
E
Salardini
Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
M
M
Arbabi
Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
M
M
Roohi Azizi
Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
M-R
MR
Zarrindast
Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
P
P
Mohammadinejad
Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
A
A
Zeinoddini
Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
S
S
Akhondzadeh
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods; D003866:Depressive Disorder / Q000188:drug therapy*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D020280:Sertraline / Q000627:therapeutic use; D016896:Treatment Outcome
D000928:Antidepressive Agents; D016194:Receptors, N-Methyl-D-Aspartate; D020280:Sertraline; D008559:Memantine
clinical trial; glutamate; major depression disorder; memantine