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. Theta burst stimulation (TBS), a newer form of transcranial magnetic stimulation (TMS), offers the advantage of shorter treatment duration, but its comparative efficacy against conventional TMS and sham remains uncertain. Despite growing clinical interest, prior reviews have lacked sufficient data to establish TBS as a frontline neuromodulatory option. 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. Ethical approval was not applicable due to the nature of secondary data synthesis The protocol for this systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD420251008712. 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.