Repetitive Transcranial Magnetic Stimulation in Substance Use Disorders is Safe and Tolerable: A Systematic Review of 141 Clinical Trials Including 4,299 Participants

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation intervention that has been investigated as a treatment for substance use disorder (SUD) and its co-occurring disorders. As the number of rTMS SUD clinical trials increase, the safety and tolerability profile should be assessed. In this systematic review, we investigate adverse events (AEs) of rTMS in individuals with SUD and factors that may influence their occurrence, including treatment status, and substance-use type. MethodsWe performed a systematic PubMed search to identify all controlled trials of rTMS in SUD published up to January 2025. Eligible studies were assessed, and safety information was extracted for analysis. ResultsA total of 141 controlled clinical trials with 4,299 participants were included in their active arms. rTMS trials recruited participants who were engaged in active substance use (37 studies), in the pre-treatment phase (61), in early recovery (18), or in sustained recovery (25). Twenty-two studies (15.60 %) explicitly reported no AEs adverse effects. Sixty-nine (48.94 %) studies reported only mild AEs adverse events, while only six studies (4.26%) reported moderate AEs adverse events. Thirty-five studies did not report safety-outcomes/AEs. As expected, participants reported mild and temporary AEs such as headaches, pain or discomfort under the coil, or dizziness. The most frequent side effects were headache (57 studies in active TMS vs. 32 in sham TMS), pain or discomfort at the stimulation site (34 vs. 20 studies), and dizziness (11 vs. 5 studies). These effects were generally temporary and did not require participants to stop treatment. Only nine studies reported serious side effects (7 studies in active TMS and 2 in sham TMS). Importantly, no seizures attributable to active rTMS were reported in these SUD samples. The other severe events included severe headache (5 studies), tinnitus (1), disorientation (1), and suicidal ideation (1). In total, 9 studies reported dropout due to adverse effects. Thirty-five studies (24.82%) did not report safety-outcomes/adverse-events. ConclusionOverall, rTMS in SUD samples is safe and well-tolerated regardless of recovery stage and substance. Most reported side effects were mild, self-limiting, and tolerable. This evidence supports the safety of rTMS as a potential stand-alone or adjunctive treatment for SUD. HighlightsO_LIWe reviewed 141 controlled rTMS trials with 4,299 SUD participants C_LIO_LIrTMS in SUDs is safe and well-tolerated C_LIO_LINo reports of rTMS-induced seizures among 4,299 participants C_LIO_LIMost side-effects were mild and transient (headache, scalp pain) C_LIO_LIStandardized reporting of side-effects and adverse events is needed C_LI