Effectiveness of Theta Burst Stimulation vs. Transcranial Magnetic Stimulation and Sham in Major Depressive Disorder: Updated Systematic Review and Meta-Analysis

Abstract

Background: Major depressive disorder (MDD) is a leading global cause of disability, with a substantial proportion of patients failing to respond to pharmacotherapy or psychotherapy. Objective: This study aimed to conduct an updated systematic review and meta-analysis evaluating the efficacy and safety of TBS compared to both sham stimulation and conventional TMS in adults with MDD, focusing on categorical response, percent symptom reduction, remission, and adverse events. Methods: This systematic review and meta-analysis included randomized controlled trials (RCTs) comparing TBS with sham or standard TMS in adult patients diagnosed with MDD. A comprehensive search of PubMed, CENTRAL, and EBSCO/CINAHL was performed through March 28, 2025. Primary outcome was defined as ≥50% reduction in Hamilton Rating Scale for Depression (HRSD) scores. Secondary outcomes included percent change in HRSD, remission (HRSD <11), Beck Depression Inventory (BDI) scores, and adverse events. Data were pooled using a random-effects model in Review Manager (RevMan) 5.4, with quality assessed via the Cochrane Risk of Bias tool and GRADE. Results: Fourteen RCTs met inclusion criteria. TBS showed significantly higher response rates than sham (RR = 2.40, 95% CI: 1.27–4.55, p = 0.007) and was comparable to standard TMS (RR = 1.02, p = 0.80). Percent change in HRSD and MADRS outcomes favored TBS, while adverse event rates did not differ significantly between groups. Conclusion: TBS is a clinically effective and time-efficient intervention for MDD, offering comparable or superior outcomes to conventional TMS and significantly outperforming sham. Its favorable tolerability and shorter session duration support broader clinical application and integration into psychiatric care settings.