Adjunctive tDCS for treatment-refractory auditory hallucinations in schizophrenia: A meta-analysis of randomized, double-blinded, sham-controlled studies.

OBJECTIVE: Treatment-refractory auditory hallucinations (TRAH) in schizophrenia often do not improve with pharmacotherapy. We performed a meta-analysis of randomized, double-blind, sham-controlled clinical trials (RCTs) that systematically examined the therapeutic effects and tolerability of adjunctive active versus sham active transcranial direct current stimulation (tDCS) for auditory hallucinations as measured by the Auditory Hallucination Rating Scale (AHRS) in schizophrenia patients with TRAH. METHODS: Relevant data were extracted, checked and analyzed using the Review Manager, Version 5.3 by three independent investigators. RESULTS: Eight double-blind RCTs covering 329 schizophrenia patients (168 in active tDCS group, 161 in sham tDCS group) were included. Although no advantage of active tDCS on auditory hallucinations [7 RCTs, n = 224; standardized mean difference (SMD): - 0.33 (95% confidence interval (CI): - 0.71, 0.05), P = 0.09; I2 = 46%] was found compared to sham, subgroup analyses revealed that active tDCS with twice-daily stimulation [6 RCTs, n = 198; SMD: - 0.42 (95%CI: -0.82, -0.02), P = 0.04; I2 = 44%] and active tDCS with ≥ 10 stimulation sessions [6 RCTs, n = 198; SMD: - 0.42 (95%CI: -0.82, -0.02), P = 0.04; I2 = 44%] showed a significantly better therapeutic effect than sham in improving auditory hallucinations symptoms. Meta-analyses of total psychopathology and discontinuation due to any reason were not significantly different between the active and sham tDCS groups. CONCLUSION: This meta-analysis demonstrated that the effects of tDCS for auditory hallucinations symptoms were influenced by the tDCS parameters. Twice-daily stimulation and ≥ 10 stimulation sessions may be needed to improve auditory hallucinations symptoms in schizophrenia with TRAH.

Adjunctive metformin for antipsychotic-induced dyslipidemia: a meta-analysis of randomized, double-blind, placebo-controlled trials.

Antipsychotic-induced dyslipidemia could increase the risk of cardiovascular diseases. This is a meta-analysis of randomized double-blind placebo-controlled trials to examine the efficacy and safety of adjunctive metformin for dyslipidemia induced by antipsychotics in schizophrenia. The standardized mean differences (SMDs) and risk ratios (RRs) with their 95% confidence intervals (CIs) were calculated using the random-effects model with the RevMan 5.3 version software. The primary outcome was the change of serum lipid level. Twelve studies with 1215 schizophrenia patients (592 in metformin group and 623 in placebo group) were included and analyzed. Adjunctive metformin was significantly superior to placebo with regards to low density lipoprotein cholesterol (LDL-C) [SMD: -0.37 (95%CI:-0.69, -0.05), P = 0.02; I2 = 78%], total cholesterol [SMD: -0.47 (95%CI:-0.66, -0.29), P < 0.00001; I2 = 49%], triglyceride [SMD: -0.33 (95%CI:-0.45, -0.20), P < 0.00001; I2 = 0%], and high density lipoprotein cholesterol [SMD: 0.29 (95%CI:0.02, 0.57), P = 0.03; I2 = 69%]. The superiority of metformin in improving LDL-C level disappeared in a sensitivity analysis and 80% (8/10) of subgroup analyses. Metformin was significantly superior to placebo with regards to decrease in body weight, body mass index, glycated hemoglobin A1c, fasting insulin, and homeostasis model assessment-insulin resistance (P = 0.002-0.01), but not regarding changes in waist circumference, waist-to-hip rate, leptin, fasting glucose, and blood pressure (P = 0.07-0.33). The rates of discontinuation due to any reason [RR: 0.97 (95%CI: 0.66, 1.43), P = 0.89; I2 = 0%] was similar between the two groups. Adjunctive metformin could be useful to improve total cholesterol and triglyceride levels, but it was not effective in improving LDL-C level in schizophrenia.