Transcranial Magnetic Stimulation for Bipolar Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials: Stimulation magnétique transcrânienne dans les cas de dépression bipolaire : une revue systématique et une méta-analyse d’essais contrôlés à répartition aléatoire

Introduction Bipolar depression is disabling and often inadequately responsive to medication alone. The current efficacy evidence of transcranial magnetic stimulation (TMS) for bipolar depression is conflicting. Therefore, we synthesized randomized controlled trials (RCTs) that tested the efficacy, safety, and tolerability of TMS for bipolar depression. Methods We searched MEDLINE/EMBASE/Cochrane/PsycINFO/gray literature (01/10/2025) for RCTs comparing any TMS protocol with sham. Co-primary outcomes were depressive symptoms, all-cause discontinuation; secondary outcomes were response, remission. Risk of bias (RoB) was assessed with RoB-2. Random-effects models estimated standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (95%CI), alongside sensitivity, subgroup, and meta-regression analyses. Results Nineteen comparisons from 17 RCTs (N = 563; TMS = 293, sham = 270; mean N TMS = 15.4, sham = 15.9; mean duration = 2.40 weeks; RoB “low” = 35%, “some concerns” = 65%) were included. Among trials reporting subtypes (k = 13), 41.8% of participants had bipolar I disorder, and 58.2% had bipolar II disorder. The left dorsolateral prefrontal cortex was the most common target (k = 12). TMS reduced depressive symptoms versus sham (SMD = −0.34; 95%CI = −0.58 to −0.11), with no difference in all-cause discontinuation. TMS was favoured for response (RR = 1.41; 95%CI = 1.10 to 1.80) and remission (RR = 1.54; 95%CI = 1.06 to 2.23). However, these effects were not consistently confirmed in sensitivity or subgroup analyses by RoB, TMS type, stimulation site, or treatment resistance. Overall, 15 comparisons (88.2%) did not show superiority of TMS over sham for depressive symptoms at the individual trial level. No seizures or serious adverse events occurred; adverse events did not differ from sham. Meta-regression suggested a greater number of total pulses was associated with greater depressive symptom reduction (β = −0.018; p = .00017). Conclusions TMS shows a small meta-analytic antidepressant effect and acceptable tolerability in bipolar depression despite most individual trials being negative. However, subgroups and sensitivity findings did not support TMS as an efficacious treatment at current doses. Further testing via larger RCTs with higher-dose protocols is warranted.