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

Taro Kishi, Yuki Matsuda, Nakao Iwata

Research output: Contribution to journalArticle

16 Citations (Scopus)

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, I2 = 88%; N = 7, n = 367) in the Positive and Negative Syndrome Scale general subscale (MD = −1.62, p = 0.002, I2 = 0%; N = 4, n = 151) and Mini-Mental Status Examination score (MD = −3.07, p < 0.0001, I2 = 21%; N = 3, n = 83), there were no statistically significant differences in the amelioration of overall (SMD = −0.75, p = 0.06, I2 = 86%; N = 5, n = 271), positive (SMD = −0.46, p = 0.07, I2 = 80%; N = 7, n = 367), and depressive symptoms (SMD = −0.127, p = 0.326, I2 = 0%; N = 4, n = 201); all-cause discontinuation (RR = 1.34, p = 0.31, I2 = 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 (I2 = 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.

Original languageEnglish
Pages (from-to)2113-2125
Number of pages13
JournalPsychopharmacology
Volume234
Issue number14
DOIs
Publication statusPublished - 01-07-2017

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Memantine
Neurobehavioral Manifestations
Antipsychotic Agents
Meta-Analysis
Schizophrenia
Placebos
Therapeutics
Odds Ratio
Risperidone
Dizziness
Constipation
Nausea
Fatigue
Headache
Young Adult
Randomized Controlled Trials
Regression Analysis
Depression
Safety

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

@article{b0ddaafee84948f58575ce928b8808c4,
title = "Memantine add-on to antipsychotic treatment for residual negative and cognitive symptoms of schizophrenia: a meta-analysis",
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, I2 = 88{\%}; N = 7, n = 367) in the Positive and Negative Syndrome Scale general subscale (MD = −1.62, p = 0.002, I2 = 0{\%}; N = 4, n = 151) and Mini-Mental Status Examination score (MD = −3.07, p < 0.0001, I2 = 21{\%}; N = 3, n = 83), there were no statistically significant differences in the amelioration of overall (SMD = −0.75, p = 0.06, I2 = 86{\%}; N = 5, n = 271), positive (SMD = −0.46, p = 0.07, I2 = 80{\%}; N = 7, n = 367), and depressive symptoms (SMD = −0.127, p = 0.326, I2 = 0{\%}; N = 4, n = 201); all-cause discontinuation (RR = 1.34, p = 0.31, I2 = 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 (I2 = 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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Memantine add-on to antipsychotic treatment for residual negative and cognitive symptoms of schizophrenia : a meta-analysis. / Kishi, Taro; Matsuda, Yuki; Iwata, Nakao.

In: Psychopharmacology, Vol. 234, No. 14, 01.07.2017, p. 2113-2125.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Memantine add-on to antipsychotic treatment for residual negative and cognitive symptoms of schizophrenia

T2 - a meta-analysis

AU - Kishi, Taro

AU - Matsuda, Yuki

AU - Iwata, Nakao

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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, I2 = 88%; N = 7, n = 367) in the Positive and Negative Syndrome Scale general subscale (MD = −1.62, p = 0.002, I2 = 0%; N = 4, n = 151) and Mini-Mental Status Examination score (MD = −3.07, p < 0.0001, I2 = 21%; N = 3, n = 83), there were no statistically significant differences in the amelioration of overall (SMD = −0.75, p = 0.06, I2 = 86%; N = 5, n = 271), positive (SMD = −0.46, p = 0.07, I2 = 80%; N = 7, n = 367), and depressive symptoms (SMD = −0.127, p = 0.326, I2 = 0%; N = 4, n = 201); all-cause discontinuation (RR = 1.34, p = 0.31, I2 = 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 (I2 = 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.

AB - 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, I2 = 88%; N = 7, n = 367) in the Positive and Negative Syndrome Scale general subscale (MD = −1.62, p = 0.002, I2 = 0%; N = 4, n = 151) and Mini-Mental Status Examination score (MD = −3.07, p < 0.0001, I2 = 21%; N = 3, n = 83), there were no statistically significant differences in the amelioration of overall (SMD = −0.75, p = 0.06, I2 = 86%; N = 5, n = 271), positive (SMD = −0.46, p = 0.07, I2 = 80%; N = 7, n = 367), and depressive symptoms (SMD = −0.127, p = 0.326, I2 = 0%; N = 4, n = 201); all-cause discontinuation (RR = 1.34, p = 0.31, I2 = 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 (I2 = 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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