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Adjunctive memantine for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials

Published online by Cambridge University Press:  22 May 2017

W. Zheng ,
X-H. Li ,
X-H. Yang ,
D-B. Cai ,
G. S. Ungvari ,
C. H. Ng ,
S-B. Wang ,
Y-Y. Wang ,
Y-P. Ning  and
Y-T. Xiang
W. Zheng
Affiliation:
The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China
X-H. Li
Affiliation:
The National Clinical Research Center for Mental Disorders, China Center of Depression, Beijing Institute for Brain Disorders & Mood Disorders Center, Beijing Anding Hospital, Capital Medical University, Beijing, China
X-H. Yang
Affiliation:
The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China
D-B. Cai
Affiliation:
Clinics of Chinese Medicine, the First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
G. S. Ungvari
Affiliation:
The University of Notre Dame Australia/Marian Centre, Perth, Australia School of Psychiatry & Clinical Neurosciences, University of Western Australia, Perth, Australia
C. H. Ng
Affiliation:
Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia
S-B. Wang
Affiliation:
Faculty of Health Sciences, Unit of Psychiatry, University of Macau, Macao SAR, China
Y-Y. Wang
Affiliation:
Faculty of Health Sciences, Unit of Psychiatry, University of Macau, Macao SAR, China
Y-P. Ning*
Affiliation:
The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China
Y-T. Xiang*
Affiliation:
Faculty of Health Sciences, Unit of Psychiatry, University of Macau, Macao SAR, China
*
*Address for correspondence: Dr Y-T. Xiang, M.D., Ph.D., Faculty of Health Sciences, University of Macau, Avenida da Universidade, 3/F, Building E12, Taipa, Macau SAR, China. (Email: xyutly@gmail.com) Or Dr Y-P. Ning, M.D., Ph.D., The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China. (Email: ningjeny@126.com)
*Address for correspondence: Dr Y-T. Xiang, M.D., Ph.D., Faculty of Health Sciences, University of Macau, Avenida da Universidade, 3/F, Building E12, Taipa, Macau SAR, China. (Email: xyutly@gmail.com) Or Dr Y-P. Ning, M.D., Ph.D., The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China. (Email: ningjeny@126.com)
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Abstract

Background

Dysfunction of N-methyl-D-aspartate receptor (NMDAR) is involved in the pathophysiology of schizophrenia. A meta-analysis of randomized controlled trials (RCTs) was conducted to examine the efficacy and safety of memantine, a non-competitive NMDAR antagonist, in the treatment of schizophrenia.

Methods

Standardized/weighted mean differences (SMDs/WMDs), risk ratio (RR), and their 95% confidence intervals (CIs) were calculated and analyzed.

Results

Included in the meta-analysis were eight RCTs (n = 452) of 11.5 ± 2.6 weeks duration, with 229 patients on memantine (20 mg/day) and 223 patients on placebo. Adjunctive memantine outperformed placebo in the measures of Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale negative symptoms [SMD: −0.63 (95% CI −1.10 to −0.16), p = 0.009, I2 = 77%], but not in the total, positive and general symptoms [SMD: −0.46 to −0.08 (95% CI −0.93 to 0.22), p = 0.06–0.60, I2 = 0–74%] or the Clinical Global Impression Severity Scale [WMD: 0.04 (95% CI −0.24 to 0.32), p = 0.78]. The negative symptoms remained significant after excluding one outlying RCT [SMD: −0.41 (95% CI −0.72 to −0.11), p = 0.008, I2 = 47%]. Compared with the placebo group, adjunctive memantine was associated with significant improvement in neurocognitive function using the Mini-Mental State Examination (MMSE) [WMD: 3.09, (95% CI 1.77–4.42), p < 0.00001, I2 = 22%]. There was no significant difference in the discontinuation rate [RR: 1.34 (95% CI 0.76–2.37), p = 0.31, I2 = 0%] and adverse drug reactions between the two groups.

Conclusions

This meta-analysis showed that adjunctive memantine appears to be an efficacious and safe treatment for improving negative symptoms and neurocognitive performance in schizophrenia. Higher quality RCTs with larger samples are warranted to confirm these findings.

Keywords

Memantinemeta-analysisnegative symptomsNMDA receptor antagonistsschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 1 , January 2018 , pp. 72 - 81
Copyright
Copyright © Cambridge University Press 2017 

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Footnotes

†

These authors contributed equally to this work.

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