Efficacy, effectiveness and safety of transcranial magnetic stimulation for bipolar depression: A systematic review and meta-analysis
Bibliographic record
Abstract
STRUCTURED ABSTRACT 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.013 | 0.033 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.019 | 0.033 |
| Bibliometrics | 0.008 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".