Efficacy and Safety of Intermittent Theta Burst Stimulation and High-Frequency Repetitive Transcranial Magnetic Stimulation for Major Depressive Disorder: A Systematic Meta-Analysis

Aims/Background High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and intermittent theta burst stimulation (iTBS) are emerging neuromodulation techniques for major depressive disorder (MDD). However, clinical trials directly comparing their efficacy are limited. This meta-analysis aimed to evaluate the antidepressant effects and safety profiles of iTBS versus HF-rTMS for MDD. Methods A systematic literature search was conducted in major databases to identify randomized controlled trials (RCTs) comparing iTBS and HF-rTMS for MDD. The primary outcome measures were response rate, remission rate, and common side effects. Meta-analysis was performed using fixed-effects and random-effects models. Publication bias was assessed. Results Seven RCTs were included in the meta-analysis. No significant differences were found in response rate (odds ratio (OR) 0.97, 95% confidence interval (95% CI) 0.81 to 1.16, p = 0.75) or remission rate (OR 1.06, 95% CI 0.85 to 1.31, p = 0.62) between iTBS and HF-rTMS. Both active stimulations showed significantly higher response rates than sham treatment. The odds of response were 4-5 times greater for iTBS versus sham (OR 4.84, 95% CI 2.66 to 8.80, p < 0.001) and 3-4 times greater for HF-rTMS versus sham (OR 3.85, 95% CI 2.08 to 7.13, p < 0.001). No differences in common side effects such as headache were observed between iTBS and HF-rTMS. Conclusion iTBS and HF-rTMS have comparable efficacy and safety profiles in treating MDD based on current evidence. Both neuromodulation techniques are superior to sham stimulation. iTBS could be considered an alternative to HF-rTMS, with the advantage of shorter daily treatment duration. Further large RCTs with long-term follow-up are warranted to confirm these findings.