NMDA receptor antagonists interventions in schizophrenia: Meta-analysis of randomized, placebo-controlled trials

Taro Kishi, Nakao Iwata

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Background: We examined whether N-methyl d-aspartate (NMDA) receptor antagonists as adjunctive therapy have therapeutic potential for schizophrenia treatment. Method: Systematic review of PubMed, Cochrane Library, PsycINFO and Google Scholar up until October 2012 and meta-analysis of randomized placebo-controlled trials were performed. Risk ratio (RR), 95% confidence intervals (CI), numbers-needed-to-harm (NNH), and standardized mean difference (SMD) were calculated. Results: Results were across 8 studies and 406 patients (85.5% schizophrenia related disorder and 14.5% bipolar disorder) were included (amantadine: 5 trials and 220 patients, memantine: 3 trials and 186 patients). NMDA receptor antagonists (NMDAR-ANTs) as adjunctive therapy were not superior to placebo in overall (SMD=-0.25, CI=-0.72, 0.23, p=0.31, N=6, n=347), positive symptoms (SMD=-0.20, CI=-0.70, 0.31, p=0.44, N=4, n=205), and negative symptoms (SMD=-0.69, CI=-1.65, 0.27, p=0.16, N=4, n=205), and Clinical Global Impression Severity scale (SMD=-0.27, CI=-1.20, 0.65, p=0.56, N=3, n=177). There was also no significant difference in discontinuation rate between NMDAR-ANTs and placebo treatments (all cause: RR=1.23, CI=0.89-1.70, p=0.20, N=8, n=396, side effects: RR=1.86, CI=0.84-4.13, p=0.13, N=6, n=359, inefficacy/worsening psychosis: RR=0.70, CI=0.20-2.38, p=0.56, N=7, n=380). However, memantine was favorable compared with placebo in Mini-Mental State Examination in schizophrenia (SMD=-0.77, CI=-1.27,-0.28, p=0.002, N=3, n=71). While NMDAR-ANTs caused weight loss compared with placebo (SMD=-0.42, CI=-0.73,-0.11, p=0.008, N=3, n=165), amantadine caused more frequent insomnia than placebo (RR=3.83, CI=1.41-10.38, p=0.008, NNH=9, p=0.002, N=2, n=147). Conclusion: Our results indicate that NMDAR-ANTs as adjunctive therapy may improve cognitive function in patients with schizophrenia. Because the included studies were small, a replication study using larger samples is needed.

Original languageEnglish
Pages (from-to)1143-1149
Number of pages7
JournalJournal of Psychiatric Research
Volume47
Issue number9
DOIs
Publication statusPublished - 01-01-2013

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Meta-Analysis
Schizophrenia
Randomized Controlled Trials
Placebos
Confidence Intervals
Odds Ratio
N-Methyl-D-Aspartate Receptors
Memantine
Amantadine
aspartic acid receptor
Therapeutics
Sleep Initiation and Maintenance Disorders
Bipolar Disorder
PubMed
Psychotic Disorders
Cognition
Libraries
Weight Loss

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

@article{8c41382d11574ca5b2578b96d0074881,
title = "NMDA receptor antagonists interventions in schizophrenia: Meta-analysis of randomized, placebo-controlled trials",
abstract = "Background: We examined whether N-methyl d-aspartate (NMDA) receptor antagonists as adjunctive therapy have therapeutic potential for schizophrenia treatment. Method: Systematic review of PubMed, Cochrane Library, PsycINFO and Google Scholar up until October 2012 and meta-analysis of randomized placebo-controlled trials were performed. Risk ratio (RR), 95{\%} confidence intervals (CI), numbers-needed-to-harm (NNH), and standardized mean difference (SMD) were calculated. Results: Results were across 8 studies and 406 patients (85.5{\%} schizophrenia related disorder and 14.5{\%} bipolar disorder) were included (amantadine: 5 trials and 220 patients, memantine: 3 trials and 186 patients). NMDA receptor antagonists (NMDAR-ANTs) as adjunctive therapy were not superior to placebo in overall (SMD=-0.25, CI=-0.72, 0.23, p=0.31, N=6, n=347), positive symptoms (SMD=-0.20, CI=-0.70, 0.31, p=0.44, N=4, n=205), and negative symptoms (SMD=-0.69, CI=-1.65, 0.27, p=0.16, N=4, n=205), and Clinical Global Impression Severity scale (SMD=-0.27, CI=-1.20, 0.65, p=0.56, N=3, n=177). There was also no significant difference in discontinuation rate between NMDAR-ANTs and placebo treatments (all cause: RR=1.23, CI=0.89-1.70, p=0.20, N=8, n=396, side effects: RR=1.86, CI=0.84-4.13, p=0.13, N=6, n=359, inefficacy/worsening psychosis: RR=0.70, CI=0.20-2.38, p=0.56, N=7, n=380). However, memantine was favorable compared with placebo in Mini-Mental State Examination in schizophrenia (SMD=-0.77, CI=-1.27,-0.28, p=0.002, N=3, n=71). While NMDAR-ANTs caused weight loss compared with placebo (SMD=-0.42, CI=-0.73,-0.11, p=0.008, N=3, n=165), amantadine caused more frequent insomnia than placebo (RR=3.83, CI=1.41-10.38, p=0.008, NNH=9, p=0.002, N=2, n=147). Conclusion: Our results indicate that NMDAR-ANTs as adjunctive therapy may improve cognitive function in patients with schizophrenia. Because the included studies were small, a replication study using larger samples is needed.",
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NMDA receptor antagonists interventions in schizophrenia : Meta-analysis of randomized, placebo-controlled trials. / Kishi, Taro; Iwata, Nakao.

In: Journal of Psychiatric Research, Vol. 47, No. 9, 01.01.2013, p. 1143-1149.

Research output: Contribution to journalArticle

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T1 - NMDA receptor antagonists interventions in schizophrenia

T2 - Meta-analysis of randomized, placebo-controlled trials

AU - Kishi, Taro

AU - Iwata, Nakao

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N2 - Background: We examined whether N-methyl d-aspartate (NMDA) receptor antagonists as adjunctive therapy have therapeutic potential for schizophrenia treatment. Method: Systematic review of PubMed, Cochrane Library, PsycINFO and Google Scholar up until October 2012 and meta-analysis of randomized placebo-controlled trials were performed. Risk ratio (RR), 95% confidence intervals (CI), numbers-needed-to-harm (NNH), and standardized mean difference (SMD) were calculated. Results: Results were across 8 studies and 406 patients (85.5% schizophrenia related disorder and 14.5% bipolar disorder) were included (amantadine: 5 trials and 220 patients, memantine: 3 trials and 186 patients). NMDA receptor antagonists (NMDAR-ANTs) as adjunctive therapy were not superior to placebo in overall (SMD=-0.25, CI=-0.72, 0.23, p=0.31, N=6, n=347), positive symptoms (SMD=-0.20, CI=-0.70, 0.31, p=0.44, N=4, n=205), and negative symptoms (SMD=-0.69, CI=-1.65, 0.27, p=0.16, N=4, n=205), and Clinical Global Impression Severity scale (SMD=-0.27, CI=-1.20, 0.65, p=0.56, N=3, n=177). There was also no significant difference in discontinuation rate between NMDAR-ANTs and placebo treatments (all cause: RR=1.23, CI=0.89-1.70, p=0.20, N=8, n=396, side effects: RR=1.86, CI=0.84-4.13, p=0.13, N=6, n=359, inefficacy/worsening psychosis: RR=0.70, CI=0.20-2.38, p=0.56, N=7, n=380). However, memantine was favorable compared with placebo in Mini-Mental State Examination in schizophrenia (SMD=-0.77, CI=-1.27,-0.28, p=0.002, N=3, n=71). While NMDAR-ANTs caused weight loss compared with placebo (SMD=-0.42, CI=-0.73,-0.11, p=0.008, N=3, n=165), amantadine caused more frequent insomnia than placebo (RR=3.83, CI=1.41-10.38, p=0.008, NNH=9, p=0.002, N=2, n=147). Conclusion: Our results indicate that NMDAR-ANTs as adjunctive therapy may improve cognitive function in patients with schizophrenia. Because the included studies were small, a replication study using larger samples is needed.

AB - Background: We examined whether N-methyl d-aspartate (NMDA) receptor antagonists as adjunctive therapy have therapeutic potential for schizophrenia treatment. Method: Systematic review of PubMed, Cochrane Library, PsycINFO and Google Scholar up until October 2012 and meta-analysis of randomized placebo-controlled trials were performed. Risk ratio (RR), 95% confidence intervals (CI), numbers-needed-to-harm (NNH), and standardized mean difference (SMD) were calculated. Results: Results were across 8 studies and 406 patients (85.5% schizophrenia related disorder and 14.5% bipolar disorder) were included (amantadine: 5 trials and 220 patients, memantine: 3 trials and 186 patients). NMDA receptor antagonists (NMDAR-ANTs) as adjunctive therapy were not superior to placebo in overall (SMD=-0.25, CI=-0.72, 0.23, p=0.31, N=6, n=347), positive symptoms (SMD=-0.20, CI=-0.70, 0.31, p=0.44, N=4, n=205), and negative symptoms (SMD=-0.69, CI=-1.65, 0.27, p=0.16, N=4, n=205), and Clinical Global Impression Severity scale (SMD=-0.27, CI=-1.20, 0.65, p=0.56, N=3, n=177). There was also no significant difference in discontinuation rate between NMDAR-ANTs and placebo treatments (all cause: RR=1.23, CI=0.89-1.70, p=0.20, N=8, n=396, side effects: RR=1.86, CI=0.84-4.13, p=0.13, N=6, n=359, inefficacy/worsening psychosis: RR=0.70, CI=0.20-2.38, p=0.56, N=7, n=380). However, memantine was favorable compared with placebo in Mini-Mental State Examination in schizophrenia (SMD=-0.77, CI=-1.27,-0.28, p=0.002, N=3, n=71). While NMDAR-ANTs caused weight loss compared with placebo (SMD=-0.42, CI=-0.73,-0.11, p=0.008, N=3, n=165), amantadine caused more frequent insomnia than placebo (RR=3.83, CI=1.41-10.38, p=0.008, NNH=9, p=0.002, N=2, n=147). Conclusion: Our results indicate that NMDAR-ANTs as adjunctive therapy may improve cognitive function in patients with schizophrenia. Because the included studies were small, a replication study using larger samples is needed.

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