A meta-analysis published in Schizophrenia Research examined the efficacy of noninvasive brain stimulation techniques, including transcranial magnetic stimulation and transcranial direct current stimulation, for negative symptoms of schizophrenia.

Compared with electroconvulsive therapy, noninvasive brain stimulation modulates more targeted, controlled areas of the brain and has seen an increase in popularity over the last 2 decades.

The authors searched the Medline and Cochrane Library databases to identify 31 randomized, controlled trials comprising 1272 patients. Trial quality was assessed using the Jadad scale as well as on the basis of methods of randomization, blinding, and sham stimulation. Case reports and trials evaluating effects on conditions other than schizophrenia were excluded from the analysis.

Among these trials, 24 evaluated repetitive transcranial magnetic stimulation, 7 evaluated transcranial direct current stimulation, and 1 evaluated transcutaneous auricular vagus nerve stimulation. No trials that focused on the techniques of trigeminal nerve stimulation, deep brain stimulation, or transcranial alternating current stimulation met the requirements for inclusion. In determining the safety of noninvasive brain stimulation, the authors noted similar dropout rates among patients who underwent active stimulation vs sham stimulation.

The findings of this meta-analysis suggested that both repetitive transcranial magnetic stimulation and transcranial direct current stimulation were significantly more effective than sham stimulation.

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The investigators reported low heterogeneity for the results of repetitive transcranial magnetic stimulation trials (I2=0%, P =.749) and moderate heterogeneity for transcranial direct current stimulation trials (I2=51.3%, P =.055). With only 1 qualifying transcutaneous auricular vagus nerve stimulation trial, an isolated analysis was not possible; however, the overall heterogeneity across all 31 trials remained low at I2=2.3%.

Noninvasive brain stimulation is still considered controversial, and the trials included in the observation analysis did not control for depression scores. For future studies, the authors noted especially the need for research on the techniques’ longevity, which is still not understood.


Osoegawa C, Gomes JS, Grigolon RB, et al. Non-invasive brain stimulation for negative symptoms in schizophrenia: an updated systematic review and meta-analysis [published online February 4, 2018]. Schizophr Res. doi:10.1016/j.schres.2018.01.010