The efficacy of repetitive transcranial magnetic stimulation (rTMS) for bipolar depression: A systematic review and meta-analysis

Background: Repetitive transcranial magnetic stimulation (rTMS) has established efficacy in the treatment of unipolar depression and a growing evidence base in the treatment of bipolar depression. The objective of this study was to provide an estimate of the efficacy of rTMS in bipolar depression as an up to date synthesis of this literature is lacking. Methods: We conducted a systematic review of the sham-controlled randomized controlled trial (RCT) literature examining rTMS in bipolar depression. Studies were included if they included participants with bipolar depression in both shamand active arms. The primary outcome parameter was rate of clinical response, defined as a 50% reduction as compared to baseline, on an established depression rating scale. Quantitative synthesis was performed using the Maentel-Haenszel random effects model. Results: Data from a total of 274 patients from 14 studies were retained in the quantitative synthesis. The response rates were higher in rTMS compared to sham treatment (odds ratio (OR) = 2.72. 95%CI: 1.44-5.14). When stimulation protocols were analysed separately, statistically significant clinical response was only observed for high-frequency rTMS over the left dorsolateral prefrontal cortex (OR = 2.57, 95%CI: 1.17-5.66). Limitations: Most data was extracted from trials including very few participants with bipolar depression (predominantly unipolar depression samples). Large confirmatory RCTs of rTMS specifically for bipolar depression are lacking. Conclusion: rTMS seems effective in the treatment of bipolar depression, but dedicated and adequately powered RCTs are needed in order to firmly conclude that rTMS should be offered routinely for the treatment of bipolar depression.