O011
Efficacy of Accelerated Intermittent Theta Burst Stimulation (aiTBS) for Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
B. R. Yamamoto 1,*, J. M. Santos 1, A. R. Brunoni 1
1Universidade de São Paulo, São Paulo, Brazil
Introduction: Theta burst stimulation (TBS) is a more time-efficient alternative to repetitive transcranial magnetic stimulation (rTMS) for depression, especially in resistant cases. Conventional protocols, however, require weeks of daily visits, limiting adherence. Accelerated intermittent TBS (aiTBS, ≥2 sessions/day) seeks to shorten treatment and improve outcomes, but evidence remains limited, warranting systematic evaluation of its efficacy, safety, and clinical utility.
Objectives: To assess the efficacy of aTBS for major depressive disorder (MDD) and bipolar depression (BD); to compare the effectiveness of hyper-accelerated versus moderately accelerated schedules; to investigate potential sources of heterogeneity from subgroup analyses, including targeting method (e.g. neuronavigated approaches), acceleration schedule and type of TBS protocol.
Methods: This Systematic Review and meta-analysis followed PRISMA guidelines and was registered on PROSPERO (CRD420251081143). PubMed, Embase, Cochrane CENTRAL, ClinicalTrials.gov, and MedRxiv were searched up to July 2025. Eligibility criteria included randomized controlled trials (RCTs) enrolling adults (18–65 years) with MDD or BD treated with any aTBS protocol versus sham. The primary outcome was depressive symptom reduction; secondary outcomes were response and remission rates. Random-effects pairwise meta-analyses were performed; risk of bias was assessed with Cochrane RoB-2.
Results: Thirteen sham-controlled RCTs (n=488) were included. Compared with sham, aiTBS significantly reduced depressive symptoms (Hedges’ g = -0.60; 95% CI [-0.96, -0.24]; p=0.0011), a medium-to-large beneficial effect according to Cohen's benchmarks. Heterogeneity was moderate (I²=64.1%, 95% CI [35.0–80.2]) (figure 1); leave-one-out analyses confirmed robustness. No evidence of publication bias was detected (Egger’s p=0.66). Response rates (10 RCTs, n=373) (figure 2) favored aiTBS (RR = 2.00; 95% CI [1.39, 2.89]; p=0.0002) with low heterogeneity (I²=28.5%). Remission rates (9 RCTs, n=360) (figure 3) were nearly doubled (RR = 1.97; 95% CI [1.00, 3.86]; p=0.049), with low-to-moderate heterogeneity (I²=34.5%). Subgroup analyses suggested stronger effects with functional connectivity-based targeting, higher stimulation doses (≥50 sessions, ≥90,000 pulses), 10 sessions/day, and 50-minute intersession intervals.
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Conclusions: aiTBS appears to be an effective and well-tolerated intervention for depression, providing significant reductions in symptoms and doubling response and remission rates. Efficacy is influenced by stimulation dose and target localization. These findings support aTBS as a rapid-acting, safe, and clinically relevant neuromodulation strategy, with potential to enhance adherence and accessibility in psychiatric care.
Disclosure of Interest: None Declared