Meta-Analysis To Evaluate The Efficacy Of Glutamatergic Drugs For The Treatment Of Schizophrenia

BackgroundSchizophrenia is a severe which is a very complex, heterogeneity is very obvious in general clinical practice, and the pathogenesis is still unknown. Patients can be manifested as positive, negative, cognitive, emotional, movement disorders and other symptoms. Among them, patients with schizophrenia cognitive impairment has been paid more and more attention. Cognitive impairment includes memory function, attention, execution, practical ability, Language ability and other aspects in the field of cognitive function, it can lead to patients’ cognitive disability and bring great economic burden for patients and their families and society. In recent years, there have been major advances in our knowledge of the role of glutamatergic neurotransmission in the pathophysiology of mental disorders, especially depression and schizophrenia.ObjectiveGlutamatergic drugs for the treatment of schizophrenia has not been exhausted. So the purpose of this study is to evaluate the clinical effect of glutamatergic drugs in the treatment of schizophrenia.MethodsClinical data of patients with schizophrenia underwent glutamatergic drugs which were randomized controlled study collected from the databases of Cochrane Collaboration, EMBASE, PubMed, China National Knowledge Infrastructure (CNKI), Wanfang and VIP database, or by manual literature searching from each database which were constucted to 2014 December. Meta analysis that recommended by Cochrane Collaboration was done for the data obtained, by using the fixed or random effects model. Meta-analyses were conducted using RevMan 5.2.7 software.ResultsIn accordance with inclusive and exclusive criteria,36 RCTs (Randomized double blind controlled trials) were included. Total 36 studies that included 2134 patients with schizophrenia underwent glutamatergic drugs. There are 31 studies about glutamate receptor agonists, the total patients is 1889, and the patients of intervention group is 1889, the placebo group is 921; There are 5 studies about glutamate receptor antagonist, the total patients is 245, and the patients of intervention group is 124, the placebo group is 121.1.The Meta analysis results showed that, compared with placebo, glutamate receptor agonist adjunctive to antipsychotic drugs were effective in the negative symptom scale score of schizophrenia (SMD=-0.53,95%CI:-0.85 to -0.21, P=0.001), but had no effect on the symptom total score (SMD=-0.31,95%CI:-0.67 to 0.05, P=0.09), positive symptom scale score (SMD=-0.21,95%CI:-0.47～0.04, P=0.10), general mental pathology score (SMD=-0.01,95%CI:-0.13～0.11, P=0.91) or cognitive symptom score (SMD=-0.41, 95%CI:-0.95～0.13, P=0.13).2.Compared with placebo, glutamate receptor antagonist adjunctive to antipsychotic drugs had no effect on the symptom total score (SMD=-0.12,95%CI:-1.05～0.81, P=0.80), positive symptom scale score (SMD=-0.05,95%CI:-0.30～0.20, P=0.71), negative symptom scale score (SMD=-0.27,95%CI:-1.25～0.72, P=0.60) or the general mental pathology score (SMD=0.47,95%CI:-0.61～1.55, P=0.39).3.In the studies of the Jadad scores more than 4 points,compared with the control group, glutamate receptor agonist adjunctive to antipsychotic drugs can improve the negative symptoms of schizophrenia patients(SMD=-0.53,95%CI:-0.99～-0.06, P=0.03); but glutamate receptor agonist for the symptom total score(SMD=-0.27, 95%CI:-0.76～0.22, P=0.28), positive symptom scale score(SMD)=-0.28, 95%CI:-0.65～0.10, P=0.15), general symptom pathology score(SMD=0.08, 95%CI:-0.06～0.22, P=0.26) and cognitive symptom score(SMD=-0.48, 95%CI:-1.46～0.49, P=0.33) of schizophrenia have no obvious improvement.4.Compared with the control group, the higher quality literature about glutamate receptor antagonist adjunctive to antipsychotic drugs for the symptom total score(SMD=-0.52,95%CI:-1.38～0.34, P=0.24),positive symptom scale score(SMD=-0.20,95%CI:-0.70～0.31, P=0.44), negative symptom scale score(SMD=-0.27,95%CI:-1.25～0.72, P=0.60) have no obvious improvement.5.Compared with the control group, the literature which have the same data type about glutamate receptor agonists adjunctive to antipsychotic drugs were effective in the symptom total score(SMDPANSS-T=-2.92,95%CIPANSS-T:-5.19～-0.66, PPANSS-T=0.01; SMDBPRS-T=-2.76,95%CIBPRS-T:-4.85～-0.67, PBPRS-T=0.01) and the negative symptom scale score(SMDPANSS-N=-2.25,95%CIPANSS-N:-3.58～-0.91, PPANSS-N0.001; SMDSANS=-5.62, 95%CISANS:-7.81～-3.43, PSANS<0.00001) of schizophrenia, while glutamate receptor agonist for the positive symptom scale score(SMDPANSS-P=-0.21,95%CIPANSS-P:-0.72～0.31, PPANSS-P=0.43),general symptom pathology(SMDPANSS-G=-0.97,95%CIPANSS-G:-2.25～0.30, PPANSS-G=0.13) and cognitive symptom score(SMDPANSS-C=-0.71, 95%CIPANSS-C:1.43～0.01, PPANSS-C=0.05) of schizophrenia have no obvious improvement.ConclusionIn comparasion of the therapeutic effects of placeto and glutamate receptor agonist for the treatment of schizophrenia. Glutamate receptor agonist for the negative symptoms of schizophrenia have a certain therapeutic effect, but for positive symptoms, total symptoms, general symptoms and cognitive symptoms have no obvious improvement. So this study still needs more clinical trials and more scientific, more reliable clinical trials to confirm.