- aiTBS was superior to sham for depressive symptoms (SMD 0.69, 95% CI [0.33 to 1.05]) across RCTs (n=704).
- Clinically meaningful benefits for response (RR 1.99, NNT 5) and remission (RR 1.77, NNT 10); discontinuation rates comparable to sham.
- Dose-response was non-linear, favouring more sessions, greater total pulses, longer intersession intervals; protocols using functional connectivity neuronavigation showed larger effects.
Brain Stimul. 2026 Jul 27:103174. doi: 10.1016/j.brs.2026.103174. Online ahead of print.
ABSTRACT
BACKGROUND: Intermittent theta-burst stimulation (iTBS) is an effective but lengthy treatment protocol for major depressive episodes (MDE). Accelerated iTBS (aiTBS) delivers multiple daily sessions to reduce total treatment duration, though heterogeneous parameters have yielded mixed results.
METHODS: We conducted a pre-registered systematic review and meta-analysis of randomized sham-controlled trials on aiTBS in adults with MDE. Primary outcomes included depressive symptom improvement (Hedges’ g) and acceptability (all-cause discontinuation). Secondary outcomes included risk ratio (RR) for response/remission rates and the number needed to treat (NNT). Exploratory analyses were conducted to assess the influence of target location, dose and blinding integrity on the outcomes, complemented by within-arm decomposition.
RESULTS: Fifteen RCTs (n=704, 62.07% female, mean age 42.76 years, 11 unipolar/4 bipolar trials) met inclusion criteria (46% low bias risk). aiTBS was superior to sham in reducing depression symptoms (SMD = 0.69, 95% CI [0.33-1.05]). Discontinuation rates were similar across groups (6.96% and 8.12%). aiTBS was significantly superior to sham for response (RR=1.99, 95% CI 1.50-2.64, NNT=5), and remission (RR=1.77, 95% CI 1.07-2.93, NNT=10). Dose-response analyses showed significant non-linear relationships between dose and response, generally favoring more sessions, more total pulses, and longer intersession intervals. Furthermore, protocols using functional connectivity-based neuronavigation showed significant larger effects.
DISCUSSION: aiTBS is an effective treatment for MDE. Further studies are warranted to investigate whether effects can be enhanced through neuronavigation and higher intensity protocols.
PMID:42508605 | DOI:10.1016/j.brs.2026.103174
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