The efficacy and tolerability of memantine for depressive symptoms in major mental diseases: A systematic review and updated meta-analysis of double-blind randomized controlled trials.

ABSTRACT

OBJECTIVE: To date, there is limited evidence on the antidepressant effects of memantine in patients with major mental diseases. We conducted a systematic review and meta-analysis to assess the efficacy of memantine in such populations. METHODS: A literature search was performed for randomized controlled trials (RCTs) from the date of their inception until September 28, 2021, using PubMed, Medline, Embase, and the Cochrane Library. Changes in depression scores were the primary outcome. The response rate and remission rate to the treatment were secondary outcomes. We also assessed the dropout rate for tolerance. RESULTS: Eleven double-blind RCTs were included with 899 participants. Memantine significantly reduced depressive symptom scores compared with the control group (k = 11, n = 899, Hedges' g = -0.17, 95% confidence interval [CI] = -0.30 to -0.04, p = 0.009) with a small effect size. For secondary outcomes, memantine did not show a significant effect on response rate nor remission rate. In the subgroup analysis, memantine significantly reduced depressive symptom scores in patients with mood disorders (k = 8, n = 673, Hedges' g = -0.17, 95% CI = -0.32 to -0.01, p = 0.035) with a small effect size, but not in patients with schizophrenia. CONCLUSION: The present meta-analysis indicates that memantine effectively alleviates depressive symptoms in patients with mood disorders with a small effect size. Furthermore, memantine is well-tolerated and acceptable.