期刊
MOLECULAR PSYCHIATRY
卷 20, 期 10, 页码 1151-1160出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2015.68
关键词
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资金
- Wiley Japan
- CIHR
- Japan Society for the Promotion of Science
- Dainippon Sumitomo Pharma
- Kyowa Hakko Kirin
- Astellas
- Dainippon Sumitomo
- Eli Lilly
- Elsevier Japan
- Janssen
- Meiji Seika
- Novartis
- Otsuka
- Department of Veteran's Affair
- Feinstein Institute for Medical Research
- GlaxoSmithKline
- National Institute of Mental Health
- Psychogenics
- Research Foundation for Mental Hygiene
- Singapore National Medical Research Council
- Asahi Kasei Pharma
- Astellas Pharmaceutical
- Daiichi Sankyo
- Dainippon-Sumitomo Pharma
- Eisai
- Janssen Pharmaceutical
- Meiji-Seika Pharma
- Mochida Pharmaceutical
- MSD
- Novartis Pharma
- Otsuka Pharmaceutical
- Pfizer
- Shionogi
- Takeda
- Tanabe Mitsubishi Pharma
- Yoshitomi Yakuhin
- Canadian Institutes of Health Research (CIHR)
- US National Institute of Health
- Ontario Mental Health Foundation
- Brain and Behavior Research Foundation
- Mexico ICyTDF
- CONACyT
- Ministry of Economic Development and Innovation of Ontario
- Ontario AHSC AFP Innovation Fund
- W Garfield Weston Foundation
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 alpha-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.
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