Non-invasive brain stimulation for negative symptoms in schizophrenia: An updated systematic review and meta-analysis

Schizophrenia is a mental disorder with significant socioeconomic burden. Although current pharmacological treatments are effective for treating positive symptoms, medications have little-to-no effect in the treatment of negative symptoms.

To assess the efficacy of non-invasive brain stimulation (NIBS) for negative symptoms in schizophrenia in randomized clinical trials (RCTs).

A systematic review in Medline and Cochrane Library databases was performed up to May 31, 2017. The primary outcome was Hedges' g for continuous scores in a random-effects model. Heterogeneity was evaluated with the I² and χ² tests. Publication bias was assessed using Begg's funnel plot.

31 RCTs (n = 1272) were included, most with small-to-modest sample sizes. Both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) were superior to sham (Hedges' g = 0.19; 95% CI 0.07-0.32; and 0.5; 0.02-0.97, respectively). Only one study evaluated the use of transcutaneous auricular vagus nerve stimulation (taVNS). The funnel plot and Eggers test showed that the risk of publication bias was low. In relation to heterogeneity, we found an I² of 0% (p = 0.749) and 51.3% (0.055) for rTMS and tDCS, respectively.

Both rTMS and tDCS were superior to sham stimulation for ameliorating negative symptoms in schizophrenia. We found no considerable heterogeneity or publication bias in our analysis, corroborating the strength of our findings. Not enough studies on other NIBS techniques, such as taVNS, were found for an isolated analysis. Further RCTs with larger sample sizes are needed to clarify the specific impact of NIBS on negative symptoms in schizophrenia.