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

• Published in: Journal of affective disorders 2022-03, Vol.301, p.400-425
• Main Authors: Wang, Wei-Li, Wang, Shen-Yi, Hung, Hao-Yuan, Chen, Mu-Hong, Juan, Chi-Hung, Li, Cheng-Ta
• Format: Article
• Language: English
• Subjects: Depressive Disorder, Major - etiology; Depressive Disorder, Major - therapy; Headache; Humans; Major depressive disorder; Meta-analysis; Randomized Controlled Trials as Topic; Safety; Systematic review; Tolerability; Transcranial magnetic stimulation; Transcranial Magnetic Stimulation - adverse effects; Transcranial Magnetic Stimulation - methods; Treatment Outcome
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2022.01.047

•This is the first systematic review and meta-analyses with randomized, sham-controlled trials that focus on the safety issue of TMS intervention in major depressive disorder.•Our meta-analysis focused on the different TMS intervention (repetitive TMS, accelerated TMS, priming TMS, deep TMS, synchronized TMS or Theta burst stimulation) related safety issues including serious adverse events, non-serious adverse events, drop out due to adverse events in the unipolar depression population.•Statistically, the high rate of non-serious adverse events including headache, discomfort and pain in the stimulation site were observed in our meta-analyses, but were mostly mild and transient after TMS treatment. Generally, the risk of seizure and mood switches in active TMS can be considered as particularly low.•Our systematic review and meta-analyses support the safety and tolerability of TMS techniques as an alternative monotherapy or as an add-on treatment for major depressive disorder. 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. Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the literature published before April 30th, 2021 and performed a random-effects meta-analyses which included drop-out due to adverse events, serious adverse events and other non-serious adverse events as primary and secondary outcomes. 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 intervention 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 intervention 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