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Published on: August 11, 2015
Accelerated intermittent theta-burst stimulation for major depressive episodes: systematic review and dose-response
Jônatas Magalhães Santos1, Brenda Rocha Yamamoto1, Rodolfo Furlan Damiano2
1Universidade de São Paulo, Faculdade de Medicina, São Paulo, Brazil.
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.
Insights
Accelerated intermittent theta-burst stimulation (aiTBS) effectively treats major depressive episodes (MDE). This faster protocol shows significant improvements in depressive symptoms, response, and remission rates compared to sham treatments.
Area of Science:
- Neuroscience
- Psychiatry
- Clinical Trials
Background:
- Intermittent theta-burst stimulation (iTBS) is effective for major depressive episodes (MDE) but time-consuming.
- Accelerated iTBS (aiTBS) offers reduced treatment duration via multiple daily sessions.
- Heterogeneous aiTBS parameters have led to inconsistent outcomes.
Purpose of the Study:
- To systematically review and meta-analyze randomized sham-controlled trials of aiTBS for MDE.
- To assess the efficacy and acceptability of aiTBS compared to sham.
- To explore factors influencing aiTBS effectiveness, including target location and dose.
Main Methods:
- Systematic review and meta-analysis of 15 randomized sham-controlled trials (n=704) in adults with MDE.
- Primary outcomes: depressive symptom improvement (SMD) and acceptability (discontinuation rates).
- Secondary outcomes: response/remission rates (RR, NNT), with exploratory analyses on protocol parameters.
Main Results:
- aiTBS significantly reduced depressive symptoms (SMD=0.69) and improved response (RR=1.99, NNT=5) and remission (RR=1.77, NNT=10) versus sham.
- Acceptability was comparable between aiTBS and sham groups (discontinuation rates 6.96% vs 8.12%).
- Higher session frequency, total pulses, intersession intervals, and functional connectivity neuronavigation correlated with enhanced effects.
Conclusions:
- aiTBS is a validated and effective treatment for MDE.
- Optimizing aiTBS protocols, potentially with neuronavigation and higher intensity, may further enhance treatment outcomes.
- Further research is recommended to refine aiTBS parameters for maximal efficacy.
