Evidence map›Paper›PMID 26077694›Full record

SynthesisMolecular psychiatry2015

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

Y Iwata, S Nakajima, T Suzuki, R S E Keefe, E Plitman, J K Chung, F Caravaggio, M Mimura, A Graff-Guerrero, H Uchida

Open access · bronzeAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 4 pooled it
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 4 syntheses or guidelines pooled it, 89 citations in OpenAlex.

  1. Pooled it
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  16. Add-on Sodium Benzoate andSchizophrenia bulletin open · 2024
    Article
  17. Review
  18. Glutamatergic dysfunction in Schizophrenia.Translational psychiatry · 2022
    Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Y IwataMultimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
S NakajimaMultimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
T SuzukiDepartment of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
R S E KeefeDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
E PlitmanMultimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
J K ChungMultimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
F CaravaggioMultimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
M MimuraDepartment of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
A Graff-GuerreroMultimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
H UchidaDepartment of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
Centre for Addiction and Mental Health · CAUniversity of Toronto · CAKeio University · JPDuke University Hospital · US

Funding

CIHR 141968-1CIHR 142493-1
6 · The paper itself

Abstract

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.

Indexed as

Cognition DisordersDouble-Blind MethodExcitatory Amino Acid AgentsHumansRandomized Controlled Trials as TopicReceptors, N-Methyl-D-AspartateSchizophreniaSchizophrenic PsychologySynaptic TransmissionExcitatory Amino Acid AgentsReceptors, N-Methyl-D-Aspartate

Identifiers

PMID26077694
PMCPMC5323255
OpenAlexW1583223667

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.