Safety of transcranial magnetic stimulation in unipolar depression: A systematic review and meta-analysis of randomized-controlled trials

Background: To study the safety and patients' tolerance of transcranial magnetic stimulation (TMS), we conducted a systematic review and meta- analysis of the major depressive disorder population. Methods: Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guide-lines. We searched the literature published before April 30th, 2021 and performed a random-effects meta-ana -lyses which included drop-out due to adverse events, serious adverse events and other non-serious adverse events as primary and secondary outcomes. Results: A total of 53 randomized sham-controlled trials with 3,273 participants were included. There was no increased risk of drop-out due to an adverse event (active TMS intervention group=3.3%, sham TMS intervention group=2.3%, odds ratio = 1.30, 95% CI= 0.78-2.16, P = 0.31) or a serious adverse event (active TMS inter-vention group=0.9%, sham TMS intervention group=1.5%, odds ratio = 0.67, 95% CI= 0.29-1.55, P = 0.35). Our findings suggest that TMS intervention may significantly increase the risk of non-serious adverse events including: headaches (active TMS intervention group=22.6%, sham TMS intervention group=16.2%, odds ratio = 1.48, 95% CI= 1.15-1.91, P = 0.002), discomfort (active TMS intervention group=10.9%, sham TMS inter-vention group=5.0%, odds ratio 1.98, 95% CI= 1.22-3.21, P = 0.006) and pain (active TMS intervention group=23.8%, sham TMS intervention group=5.2%, odds ratio= 8.09, 95% CI= 4.71-13.90, P < 0.001) at the stimulation site, but these non-serious events were mostly mild and transient after TMS treatment. Conclusions: These findings provide evidence for the safety and patients' tolerance of transcranial magnetic stimulation technique as an alternative monotherapy or as an add-on treatment for major depressive disorder.