Efficacy, effectiveness and safety of transcranial magnetic stimulation for bipolar depression: A systematic review and meta-analysis
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Background
Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulatory treatment cleared by Food and Drug Administration (FDA) for use in major depressive disorder (MDD). Recently, FDA granted breakthrough status for rTMS as a therapeutic option for bipolar depression (BDep). Nonetheless, efficacy and safety for BDep are not yet sufficiently established and there is no guidance regarding patient and protocol selection. Here, we systematically reviewed the literature on TMS for BDep, to synthesize the evidence on efficacy, effectiveness and safety.
Methods
We systematically searched four literature databases for studies published between 1995-2024 treating participants with acute bipolar depression. The primary outcome for meta-analysis was change in mean depression severity scores from baseline. Determinants of treatment response were assessed using meta-regression and sub-group meta-analyses.
Results
Forty-nine articles were included, representing a total of 1593 patients with BDep. Active TMS had superior antidepressant efficacy relative to sham in RCTs (Cohen’s d=0.43; 95%CI 0.21-0.64; p<0.001; N=18). Rates of treatment-emergent mania or hypomania were low and equivalent to those found for sham (OR=1.3; 95%CI 0.7-2.5). A large effect size for antidepressant effectiveness was found when pooling active arms of RCTs with data from non-controlled studies (Cohen’s d=1.40 95%CI 1.2-1.6; p<0.001; N=39), with rates of response (47.2%, 95%CI 35.3-59.1) and remission (27.1%, 95%CI 22.1-32.2) similar to those described for MDD, and preserved in sub-analyses for high frequency protocols, including iTBS, delivered to the left DLPFC, and low frequency protocols delivered to right DLPFC. Baseline illness severity, shorter illness duration and longer treatment courses were predictors of greater antidepressant effect.
Conclusions
TMS is efficacious and safe in BDep, with response and remission rates on par with unipolar depression. Longer protocols, namely with high-frequency or iTBS to the L-DLPFC and low-frequency to the R-DLPFC, have the best results, and patient selection may further improve clinical outcomes.
