Adjunctive memantine for major mental disorders: A systematic review and meta-analysis of randomized double-blind controlled trials

Wei Zheng, Xiao Min Zhu, Qing E. Zhang, Dong Bin Cai, Xin Hu Yang, Yan Ling Zhou, Gabor S. Ungvari, Chee H. Ng, Shu Hua He, Xiao Jiang Peng, Yu Ping Ning, Yu Tao Xiang

Research output: Contribution to journalReview article

Abstract

Objective: As a non-competitive N-methyl-D-aspartate receptor antagonist, memantine has been used to treat major mental disorders including schizophrenia, bipolar disorder, and major depressive disorder (MDD). This meta-analysis systematically investigated the effectiveness and tolerability of adjunctive memantine for patients with schizophrenia, bipolar disorder, and MDD. Methods: Only randomized controlled trials (RCTs) were identified and included in the study. Data of the three disorders were separately synthesized using the RevMan 5.3 software. Results: Fifteen RCTs (n = 988) examining memantine (5–20 mg/day) as an adjunct treatment for schizophrenia (9 trials with 512 patients), bipolar disorder (3 trials with 319 patients), and MDD (3 trials with 157 patients) were analyzed. Memantine outperformed the comparator regarding total psychopathology with a standardized mean difference (SMD) of −0.56 [95% confidence interval (CI): −1.01, −0.11; I2 = 76%, P = 0.01] and negative symptoms with an SMD of −0.71 (95% CI: −1.09, −0.33; I2 = 74%, P = 0.0003) in schizophrenia, but no significant effects were found with regard to positive symptoms and general psychopathology in schizophrenia, or depressive and manic symptoms in bipolar disorder or depressive symptoms in MDD. Memantine outperformed the comparator in improving cognitive performance in schizophrenia with an SMD of 1.07 (95% CI: 0.53, 1.61; P < 0.0001, I2 = 29%). No group differences were found in the rates of adverse drug reactions and discontinuation due to any reason in the three major mental disorders. Conclusions: Memantine as an adjunct treatment appears to have significant efficacy in improving negative symptoms in schizophrenia. The efficacy and safety of adjunctive memantine for bipolar disorder or MDD needs to be further examined. Review registration: PROSPERO: 42018099045.

Original languageEnglish
Pages (from-to)12-21
Number of pages10
JournalSchizophrenia Research
Volume209
DOIs
Publication statusPublished - 1 Jul 2019

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Memantine
Mental Disorders
Meta-Analysis
Schizophrenia
Major Depressive Disorder
Bipolar Disorder
Confidence Intervals
Psychopathology
Randomized Controlled Trials
Depression
N-Methyl-D-Aspartate Receptors
Drug-Related Side Effects and Adverse Reactions
Software
Safety
Therapeutics

Cite this

Zheng, Wei ; Zhu, Xiao Min ; Zhang, Qing E. ; Cai, Dong Bin ; Yang, Xin Hu ; Zhou, Yan Ling ; Ungvari, Gabor S. ; Ng, Chee H. ; He, Shu Hua ; Peng, Xiao Jiang ; Ning, Yu Ping ; Xiang, Yu Tao. / Adjunctive memantine for major mental disorders : A systematic review and meta-analysis of randomized double-blind controlled trials. In: Schizophrenia Research. 2019 ; Vol. 209. pp. 12-21.
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abstract = "Objective: As a non-competitive N-methyl-D-aspartate receptor antagonist, memantine has been used to treat major mental disorders including schizophrenia, bipolar disorder, and major depressive disorder (MDD). This meta-analysis systematically investigated the effectiveness and tolerability of adjunctive memantine for patients with schizophrenia, bipolar disorder, and MDD. Methods: Only randomized controlled trials (RCTs) were identified and included in the study. Data of the three disorders were separately synthesized using the RevMan 5.3 software. Results: Fifteen RCTs (n = 988) examining memantine (5–20 mg/day) as an adjunct treatment for schizophrenia (9 trials with 512 patients), bipolar disorder (3 trials with 319 patients), and MDD (3 trials with 157 patients) were analyzed. Memantine outperformed the comparator regarding total psychopathology with a standardized mean difference (SMD) of −0.56 [95{\%} confidence interval (CI): −1.01, −0.11; I2 = 76{\%}, P = 0.01] and negative symptoms with an SMD of −0.71 (95{\%} CI: −1.09, −0.33; I2 = 74{\%}, P = 0.0003) in schizophrenia, but no significant effects were found with regard to positive symptoms and general psychopathology in schizophrenia, or depressive and manic symptoms in bipolar disorder or depressive symptoms in MDD. Memantine outperformed the comparator in improving cognitive performance in schizophrenia with an SMD of 1.07 (95{\%} CI: 0.53, 1.61; P < 0.0001, I2 = 29{\%}). No group differences were found in the rates of adverse drug reactions and discontinuation due to any reason in the three major mental disorders. Conclusions: Memantine as an adjunct treatment appears to have significant efficacy in improving negative symptoms in schizophrenia. The efficacy and safety of adjunctive memantine for bipolar disorder or MDD needs to be further examined. Review registration: PROSPERO: 42018099045.",
keywords = "Bipolar disorder, Major depressive disorder, Memantine, NMDA receptor antagonists, Schizophrenia",
author = "Wei Zheng and Zhu, {Xiao Min} and Zhang, {Qing E.} and Cai, {Dong Bin} and Yang, {Xin Hu} and Zhou, {Yan Ling} and Ungvari, {Gabor S.} and Ng, {Chee H.} and He, {Shu Hua} and Peng, {Xiao Jiang} and Ning, {Yu Ping} and Xiang, {Yu Tao}",
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Adjunctive memantine for major mental disorders : A systematic review and meta-analysis of randomized double-blind controlled trials. / Zheng, Wei; Zhu, Xiao Min; Zhang, Qing E.; Cai, Dong Bin; Yang, Xin Hu; Zhou, Yan Ling; Ungvari, Gabor S.; Ng, Chee H.; He, Shu Hua; Peng, Xiao Jiang; Ning, Yu Ping; Xiang, Yu Tao.

In: Schizophrenia Research, Vol. 209, 01.07.2019, p. 12-21.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Adjunctive memantine for major mental disorders

T2 - A systematic review and meta-analysis of randomized double-blind controlled trials

AU - Zheng, Wei

AU - Zhu, Xiao Min

AU - Zhang, Qing E.

AU - Cai, Dong Bin

AU - Yang, Xin Hu

AU - Zhou, Yan Ling

AU - Ungvari, Gabor S.

AU - Ng, Chee H.

AU - He, Shu Hua

AU - Peng, Xiao Jiang

AU - Ning, Yu Ping

AU - Xiang, Yu Tao

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Objective: As a non-competitive N-methyl-D-aspartate receptor antagonist, memantine has been used to treat major mental disorders including schizophrenia, bipolar disorder, and major depressive disorder (MDD). This meta-analysis systematically investigated the effectiveness and tolerability of adjunctive memantine for patients with schizophrenia, bipolar disorder, and MDD. Methods: Only randomized controlled trials (RCTs) were identified and included in the study. Data of the three disorders were separately synthesized using the RevMan 5.3 software. Results: Fifteen RCTs (n = 988) examining memantine (5–20 mg/day) as an adjunct treatment for schizophrenia (9 trials with 512 patients), bipolar disorder (3 trials with 319 patients), and MDD (3 trials with 157 patients) were analyzed. Memantine outperformed the comparator regarding total psychopathology with a standardized mean difference (SMD) of −0.56 [95% confidence interval (CI): −1.01, −0.11; I2 = 76%, P = 0.01] and negative symptoms with an SMD of −0.71 (95% CI: −1.09, −0.33; I2 = 74%, P = 0.0003) in schizophrenia, but no significant effects were found with regard to positive symptoms and general psychopathology in schizophrenia, or depressive and manic symptoms in bipolar disorder or depressive symptoms in MDD. Memantine outperformed the comparator in improving cognitive performance in schizophrenia with an SMD of 1.07 (95% CI: 0.53, 1.61; P < 0.0001, I2 = 29%). No group differences were found in the rates of adverse drug reactions and discontinuation due to any reason in the three major mental disorders. Conclusions: Memantine as an adjunct treatment appears to have significant efficacy in improving negative symptoms in schizophrenia. The efficacy and safety of adjunctive memantine for bipolar disorder or MDD needs to be further examined. Review registration: PROSPERO: 42018099045.

AB - Objective: As a non-competitive N-methyl-D-aspartate receptor antagonist, memantine has been used to treat major mental disorders including schizophrenia, bipolar disorder, and major depressive disorder (MDD). This meta-analysis systematically investigated the effectiveness and tolerability of adjunctive memantine for patients with schizophrenia, bipolar disorder, and MDD. Methods: Only randomized controlled trials (RCTs) were identified and included in the study. Data of the three disorders were separately synthesized using the RevMan 5.3 software. Results: Fifteen RCTs (n = 988) examining memantine (5–20 mg/day) as an adjunct treatment for schizophrenia (9 trials with 512 patients), bipolar disorder (3 trials with 319 patients), and MDD (3 trials with 157 patients) were analyzed. Memantine outperformed the comparator regarding total psychopathology with a standardized mean difference (SMD) of −0.56 [95% confidence interval (CI): −1.01, −0.11; I2 = 76%, P = 0.01] and negative symptoms with an SMD of −0.71 (95% CI: −1.09, −0.33; I2 = 74%, P = 0.0003) in schizophrenia, but no significant effects were found with regard to positive symptoms and general psychopathology in schizophrenia, or depressive and manic symptoms in bipolar disorder or depressive symptoms in MDD. Memantine outperformed the comparator in improving cognitive performance in schizophrenia with an SMD of 1.07 (95% CI: 0.53, 1.61; P < 0.0001, I2 = 29%). No group differences were found in the rates of adverse drug reactions and discontinuation due to any reason in the three major mental disorders. Conclusions: Memantine as an adjunct treatment appears to have significant efficacy in improving negative symptoms in schizophrenia. The efficacy and safety of adjunctive memantine for bipolar disorder or MDD needs to be further examined. Review registration: PROSPERO: 42018099045.

KW - Bipolar disorder

KW - Major depressive disorder

KW - Memantine

KW - NMDA receptor antagonists

KW - Schizophrenia

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U2 - 10.1016/j.schres.2019.05.019

DO - 10.1016/j.schres.2019.05.019

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JF - Schizophrenia Research

SN - 0920-9964

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