Efficacy of Transcranial Direct Current Stimulation (tDCS) as a Treatment for Persistent Hallucinations in Patients With Schizophrenia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Hallucinations are common symptoms in schizophrenia occurring in about 60% to 80% of patients. Antipsychotics are effective in 70% to 80% of patients, while the remaining 20% to 30% of patients continue to experience persistent hallucinations despite medication. Transcranial direct current stimulation (tDCS) is a noninvasive neurostimulation technique, which has been studied as a treatment for persistent hallucinations in schizophrenia. Given the growing clinical interest in using tDCS as a treatment for persistent hallucination, we conducted a systematic review and meta-analysis of the efficacy of tDCS for alleviating hallucinations in schizophrenia. Methods: Systematic search of Medline, Embase, Cochrane Central Register of Controlled Trials, Evidence-Based Medicine Reviews, and CINAHL for relevant studies was done up to March 16, 2016. Bibliographies of retrieved articles and previous reviews were also included in the search. Eligibility criteria for study selection included randomized controlled trials that compared the efficacy of tDCS with sham stimulation for treating persistent hallucinations in patients with schizophrenia. Two reviewers independently extracted data and assessed study risk of bias. Standard mean differences across trials were pooled. Subgroup analyses were performed, and heterogeneity and potential publication bias were assessed. The GRADE system was used to evaluate the quality of evidence and confidence in the conclusions. Main outcome measure Hallucination severity evaluated by a random effects meta-analysis model. Results: Five eligible randomized sham-controlled trials involving 121 patients were included in the meta-analysis. Most patients were reported to have persistent hallucinations despite adequate antipsychotic treatment. Active tDCS (2 mA stimulation for 20 min) was administered once or twice daily, for 5 to 15 sessions, with cathode over the left temporo-parietal junction and anode over the left dorsolateral prefrontal cortex or right supraorbital ridge. The pooled effects from all trials with an overall “moderate quality” (GRADE) was −0.15 (95% CI −0.55 to 0.25), indicating no beneficial effects of tDCS on persistent hallucination in schizophrenia. The heterogeneity between trials was low (I2 = 37%) and no serious adverse effects were reported. Conclusion: Based on current moderate-quality evidence, tDCS has no beneficial effects on persistent hallucination in schizophrenia, particularly when administered once daily. Future studies should focus on twice daily stimulations to determine if tDCS is effective for treating persistent hallucinations in schizophrenia.