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Memantine add-on to antipsychotic treatment for residual negative and cognitive symptoms of schizophrenia: a meta-analysis

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Abstract

Rationale

We examined whether memantine add-on to antipsychotic treatment is beneficial in schizophrenia treatment.

Objective

This systematic review and meta-analysis aimed to achieve stronger evidence on the efficacy and safety of memantine add-on for treating schizophrenia.

Methods

We analyzed double-blind, randomized, placebo-controlled trials of memantine add-on treatment in schizophrenia patients receiving antipsychotics. The primary outcomes were amelioration of negative symptoms and all-cause discontinuation. Dichotomous outcomes are presented as risk ratios (RRs), and continuous outcomes are presented as mean differences (MDs) or standardized mean differences (SMDs).

Results

Eight studies (n = 448) were included. Although memantine add-on treatment was superior to placebo for ameliorating negative symptoms (SMD = −0.96, p = 0.006, I 2 = 88%; N = 7, n = 367) in the Positive and Negative Syndrome Scale general subscale (MD = −1.62, p = 0.002, I 2 = 0%; N = 4, n = 151) and Mini-Mental Status Examination score (MD = −3.07, p < 0.0001, I 2 = 21%; N = 3, n = 83), there were no statistically significant differences in the amelioration of overall (SMD = −0.75, p = 0.06, I 2 = 86%; N = 5, n = 271), positive (SMD = −0.46, p = 0.07, I 2 = 80%; N = 7, n = 367), and depressive symptoms (SMD = −0.127, p = 0.326, I 2 = 0%; N = 4, n = 201); all-cause discontinuation (RR = 1.34, p = 0.31, I 2 = 0%; N = 8, n = 448); and individual adverse events (fatigue, dizziness, headache, nausea, constipation) between the groups. For negative symptoms, the significant heterogeneity disappeared when risperidone studies alone were considered (I 2 = 0%). However, memantine add-on treatment remained superior to placebo (SMD = −1.29, p = 0.00001). Meta-regression analysis showed that patient age was associated with memantine-associated amelioration of negative symptoms (slope = 0.171, p = 0.0206).

Conclusions

Memantine add-on treatment may be beneficial for treating psychopathological symptoms (especially negative symptoms) in schizophrenia patients. The negative-symptom effect size may be associated with younger adult schizophrenia patients.

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Acknowledgments

We thank Dr. S. R. T. Veerman (Mental Health Service Organization North Holland North, Community Mental Health Division, Flexible Assertive Community Treatment, Alkmaar, The Netherlands) and Dr. David de Lucena (Programa de Pós-Graduação, em Medicina: Psiquiatria, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil) for providing information for this study.

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Authors and Affiliations

  1. Department of Psychiatry, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan

    Taro Kishi, Yuki Matsuda & Nakao Iwata

  2. Department of Psychiatry, National Center Hospital of Neurology and Psychiatry, Kodaira, Tokyo, 187-8551, Japan

    Yuki Matsuda

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  1. Taro Kishi
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Correspondence to Taro Kishi.

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Conflicts of interest

Drs. Kishi, Matsuda, and Iwata declare that they have no direct conflicts of interest relevant to this study. No grant support or other sources of funding were used to conduct this study or prepare this manuscript.

Dr. Kishi has received speaker’s honoraria from Daiichi Sankyo, Dainippon Sumitomo, Eisai, Eli Lilly, Janssen, Otsuka, Meiji, MSD, Tanabe-Mitsubishi (Yoshitomi), and Pfizer, and has a Fujita Health University School of Medicine research grant.

Dr. Matsuda has received speaker’s honoraria from Dainippon Sumitomo, Eisai, Eli Lilly, GlaxoSmithKline, Otsuka, Tanabe-Mitsubishi and Pfizer, and has a Grant-in-Aid for Young Scientists (B).

Dr. Iwata has received speaker’s honoraria from Astellas, Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Yoshitomi, Otsuka, Meiji, Shionogi, Novartis, and Pfizer, and had research grants from GlaxoSmithKline, Meiji, and Otsuka.

Contributors

Drs. Kishi and Matsuda had complete access to all the data used in the study and take responsibility for the integrity of the data and accuracy of the data analysis. Study concept and design were performed by Dr. Kishi. The manuscript was written by Drs. Kishi, Matsuda, and Iwata. Dr. Iwata supervised the review.

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Kishi, T., Matsuda, Y. & Iwata, N. Memantine add-on to antipsychotic treatment for residual negative and cognitive symptoms of schizophrenia: a meta-analysis. Psychopharmacology 234, 2113–2125 (2017). https://doi.org/10.1007/s00213-017-4616-7

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