Comparative efficacy and acceptability of neuromodulation procedures in the treatment of treatment-resistant depression: a network meta-analysis of randomized controlled trials

Abstract Background Nearly half of the patients with depression experience suboptimal benefits from antidepressants. Neuromodulation therapies, a kind of technology that can regulate neuronal firing activity by electrical or magnetic stimulation, were introduced to improve this situation. However, the results from clinical trials have been inconsistent. Methods We followed the extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to perform this network meta-analysis (NMA). The results were evaluated by relative risk (RR) for the response, remission, and discontinuation rates. Results In total, 49 trials with 2,941 patients were included in this study. Bilateral theta burst stimulation (TBS, RR 5.00, 95% CI 1.11-22.44), priming transcranial magnetic stimulation (pTMS, RR 2.97, 95% CI 1.20-7.39), low-frequency right repetitive transcranial magnetic stimulation (TMS) (LFR-rTMS, RR 2.62, 95% CI 1.56-4.39), high-frequency left repetitive TMS (HFL-rTMS, RR 2.18, 95% CI 1.52-3.13), and bilateral repetitive TMS (BL-rTMS, RR 3.08, 95% CI 1.78-5.31) were demonstrated to have higher respond rates than sham control. BL-rTMS (RR 3.12, 95% CI 1.06-9.09) was found to have a higher respond rate than deep brain stimulation in this NMA. All measures had the non-inferiority acceptability than the sham-control. BL-rTMS was more acceptable than bitemporal ECT (BT-ECT, RR 0.18, 95% CI 0.03-0.89), while pTMS was more acceptable than BT-ECT (RR 0.08, 95% CI 0.02-0.96), HFL-rTMS (RR 0.34, 95% CI 0.12-0.93), and deep TMS (RR 0.15, 95% CI 0.02-0.96). Conclusion Besides electroconvulsive therapy (ECT), repetitive TMS, priming TMS, and bilateral TBS proved effective for patients with treatment-resistant depression (TRD). BL-rTMS showed high efficacy and acceptability, and bilateral TBS had the potential to be the most efficacious neuromodulation measures.