Skip to main content

Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials.

Publication ,  Journal Article
Iwata, Y; Nakajima, S; Suzuki, T; Keefe, RSE; Plitman, E; Chung, JK; Caravaggio, F; Mimura, M; Graff-Guerrero, A; Uchida, H
Published in: Mol Psychiatry
October 2015

Hypofunction of N-methyl-d-aspartate (NMDA) receptors has been proposed to have an important role in the cognitive impairments observed in schizophrenia. Although glutamate modulators may be effective in reversing such difficult-to-treat conditions, the results of individual studies thus far have been inconsistent. We conducted a systematic review and meta-analysis to examine whether glutamate positive modulators have beneficial effects on cognitive functions in patients with schizophrenia. A literature search was conducted to identify double-blind randomized placebo-controlled trials in schizophrenia or related disorders, using Embase, Medline, and PsycINFO (last search: February 2015). The effects of glutamate positive modulators on cognitive deficits were evaluated for overall cognitive function and eight cognitive domains by calculating standardized mean differences (SMDs) between active drugs and placebo added to antipsychotics. Seventeen studies (N=1391) were included. Glutamate positive modulators were not superior to placebo in terms of overall cognitive function (SMD=0.08, 95% confidence interval=-0.06 to 0.23) (11 studies, n=858) nor each of eight cognitive domains (SMDs=-0.03 to 0.11) (n=367-940) in this population. Subgroup analyses by diagnosis (schizophrenia only studies), concomitant antipsychotics, or pathway of drugs to enhance the glutamatergic neurotransmission (glycine allosteric site of NMDA receptors or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors) suggested no procognitive effect of glutamate positive modulators. Further, no effect was found in individual compounds on cognition. In conclusion, glutamate positive modulators may not be effective in reversing overall cognitive impairments in patients with schizophrenia as adjunctive therapies.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

October 2015

Volume

20

Issue

10

Start / End Page

1151 / 1160

Location

England

Related Subject Headings

  • Synaptic Transmission
  • Schizophrenic Psychology
  • Schizophrenia
  • Receptors, N-Methyl-D-Aspartate
  • Randomized Controlled Trials as Topic
  • Psychiatry
  • Humans
  • Excitatory Amino Acid Agents
  • Double-Blind Method
  • Cognition Disorders
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Iwata, Y., Nakajima, S., Suzuki, T., Keefe, R. S. E., Plitman, E., Chung, J. K., … Uchida, H. (2015). Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials. Mol Psychiatry, 20(10), 1151–1160. https://doi.org/10.1038/mp.2015.68
Iwata, Y., S. Nakajima, T. Suzuki, R. S. E. Keefe, E. Plitman, J. K. Chung, F. Caravaggio, M. Mimura, A. Graff-Guerrero, and H. Uchida. “Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials.Mol Psychiatry 20, no. 10 (October 2015): 1151–60. https://doi.org/10.1038/mp.2015.68.
Iwata Y, Nakajima S, Suzuki T, Keefe RSE, Plitman E, Chung JK, et al. Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials. Mol Psychiatry. 2015 Oct;20(10):1151–60.
Iwata, Y., et al. “Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials.Mol Psychiatry, vol. 20, no. 10, Oct. 2015, pp. 1151–60. Pubmed, doi:10.1038/mp.2015.68.
Iwata Y, Nakajima S, Suzuki T, Keefe RSE, Plitman E, Chung JK, Caravaggio F, Mimura M, Graff-Guerrero A, Uchida H. Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials. Mol Psychiatry. 2015 Oct;20(10):1151–1160.

Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

October 2015

Volume

20

Issue

10

Start / End Page

1151 / 1160

Location

England

Related Subject Headings

  • Synaptic Transmission
  • Schizophrenic Psychology
  • Schizophrenia
  • Receptors, N-Methyl-D-Aspartate
  • Randomized Controlled Trials as Topic
  • Psychiatry
  • Humans
  • Excitatory Amino Acid Agents
  • Double-Blind Method
  • Cognition Disorders