Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia.

BACKGROUND: Based on the glutamatergic NMDA receptor hypofunction theory of schizophrenia, NMDA receptor modulators (NMDARMs) may have therapeutic potential in the treatment of schizophrenia. OBJECTIVE: This meta-analysis aimed to evaluate the potential of modulators of the NMDA receptor as adjunctive therapy for schizophrenia, using the results from published trials. DATA SOURCES: A primary electronic search for controlled clinical trials using NMDARMs in schizophrenia was conducted on the PubMed, Cochrane Library, EMBASE, CINAHL® and PsycINFO databases. A secondary manual search of references from primary publications was also performed. STUDY SELECTION: Inclusion criteria were the application of an established method of diagnosis, randomized case assignment, comparison of NMDARM add-on therapy with placebo, and double-blind assessment of symptoms in chronic schizophrenia using standardized rating scales. Results were based on a total sample size of 1253 cases from 29 trials that fulfilled the specified criteria. DATA EXTRACTION: Scores on rating scales or on their relevant subscales were obtained for all selected studies from published results for the minimum dataset to compute the difference between post- and pre-trial scores and their pooled standard deviation for NMDARM add-on therapy and placebo groups for negative, positive and total symptoms. RESULTS: A negative standardized mean difference (SMD) indicates therapeutic benefit in favour of NMDARM add-on therapy and all SMD results mentioned here are statistically significant. The overall effect size for NMDARMs as a group was small for negative (SMD -0.27) and medium for total (SMD -0.40) symptoms of chronic schizophrenia. Subgroup analysis revealed medium effect sizes for D-serine and N-acetyl-cysteine (NAC) for negative (SMD -0.53 and -0.45, respectively) and total (SMD -0.40 and -0.64, respectively) symptoms, and for glycine (SMD -0.66) and sarcosine (SMD -0.41) for total symptoms. As adjuvants to non-clozapine antipsychotics, additional therapeutic benefits were observed for NMDARM as a group (SMD -0.14) and glycine (SMD -0.54) for positive symptoms; D-serine (SMD -0.54), NAC (SMD -0.45) and sarcosine (SMD -0.39) for negative symptoms; and NMDARM as a group (SMD -0.38), D-serine (SMD -0.40), glycine (SMD -1.12), NAC (SMD -0.64) and sarcosine (SMD -0.53) for total symptoms. When added to clozapine, none of the drugs demonstrated therapeutic potential, while addition of glycine (SMD +0.56) worsened positive symptoms. CONCLUSIONS: Taking into consideration the number of trials and sample size in subgroup analyses, D-serine, NAC and sarcosine as adjuncts to non-clozapine antipsychotics have therapeutic benefit in the treatment of negative and total symptoms of chronic schizophrenia. While glycine improves positive and total symptoms as an adjuvant to non-clozapine antipsychotics, it worsens them when added to clozapine.

Review and meta-analysis of usage of ginkgo as an adjunct therapy in chronic schizophrenia.

This study aimed to review the roles of antioxidants in the pathophysiology of schizophrenia, whether the properties of ginkgo can ameliorate symptoms of this illness, and evaluate available literature to test this assumption. This review is based upon published works on antioxidants and ginkgo. A primary electronic search for meta-analysis on the usage of ginkgo or its derived products in schizophrenia was conducted using Pubmed, Cochrane Library, EMBASE, CINAHL, PsycINFO and AMED. Inclusion criteria were: criteria-based diagnosis of schizophrenia, randomized case assignment, use of ginkgo as an add-on therapy, and assessment using standardized rating scales to measure the state of psychopathology for negative and total symptoms of schizophrenia. Additionally, a detailed review was undertaken to investigate if antioxidants are involved in development of psychotic symptoms in schizophrenia. The six studies that fulfilled the selection criteria were constituted of 466 cases on ginkgo and 362 cases on placebo. They all used the Scale for the Assessment of Negative Symptoms (SANS) to measure negative symptoms, and the Scale for the Assessment of Positive Symptoms (SAPS) or the Brief Psychiatric Rating Scale (BPRS) to measure total symptoms. Difference between ginkgo and control groups from their pre- and post-trial scores and its pooled standard deviation were used to compute standardized mean difference (SMD). Ginkgo as an add-on therapy to antipsychotic medication produced statistically significant moderate improvement (SMD=-0.50) in total and negative symptoms of chronic schizophrenia. Ginkgo as add-on therapy ameliorates the symptoms of chronic schizophrenia. The role of antioxidants in pathogenesis of schizophrenia has also been explored.