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.

Automated summary

This study conducted a systematic review and meta-analysis to investigate the safety and patients' tolerance of transcranial magnetic stimulation (TMS) in patients with major depressive disorder. The results showed that TMS intervention was not associated with an increased risk of drop-out due to adverse events or serious adverse events. However, there was a significant increase in non-serious adverse events such as headaches, discomfort, and pain. Despite these adverse events, TMS treatment was generally well-tolerated.