Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial

Abstract

Introduction: Theta burst pattern repetitive transcranial magnetic stimulation (TBS) is increasingly applied to treat depression. TBS's brevity is well-suited to application in accelerated schedules. Sizeable trials of accelerated TBS are lacking; and optimal TBS parameters such as stimulation intensity are not established. Methods: We conducted a three arm, single blind, randomised, controlled, multi-site trial comparing accelerated bilateral TBS applied at 80 % or 120 % of the resting motor threshold and left unilateral 10 Hz rTMS. 300 patients with treatment-resistant depression (TRD) were recruited. TBS arms applied 20 bilateral prefrontal TBS sessions over 10 days, while the rTMS arm applied 20 daily sessions of 10 Hz rTMS to the left prefrontal cortex over 4 weeks. Primary outcome was depression treatment response at week 4. Results: The overall treatment response rate was 43.7 % and the remission rate was 28.2 %. There were no significant differences for response (p ¼ 0.180) or remission (p ¼ 0.316) across the three groups. Response rates between accelerated bilateral TBS applied at sub-and supra-threshold intensities were not significantly different (p ¼ 0.319). Linear mixed model analysis showed a significant effect of time (p < 0.01), but not rTMS type (p ¼ 0.680). Conclusion: This is the largest accelerated bilateral TBS study to date and provides evidence that it is effective and safe in treating TRD. The accelerated application of TBS was not associated with more rapid antidepressant effects. Bilateral sequential TBS did not have superior antidepressant effect to unilateral 10 Hz rTMS. There was no significant difference in antidepressant efficacy between sub-and suprathreshold accelerated bilateral TBS.

Letter to the editor regarding “Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial”

“…Further, the pattern of missing data is not discussed (monotonic, right censoring). For the treatment arms, the consort flow chart information on missing data is not consistent with the counts reported in table 4 [1].…”

“…The authors reported that baseline demographic characteristics were similar across the three treatment arms; however, table 3 [1] shows higher count for female participants and antidepressants use (reads 35/75, 96/10 for low intensity treatment arm, respectively). The authors didn't report model-based marginal or conditional estimates/means for treatment effects, i.e.…”

“…I read with interest the article by Chen, Fitzgerald et al [1] "Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial".…”

“…However, they only reported proportions of response and remission (set as primary outcomes at week 4 endpoint) for 252 participants (although table 4 reports counts for 253 participants). Figure 1 Consort flow chart [1] didn't inform at what time point participants dropout/withdrawal had actually occurred. The assumption of missingness at random is untested.…”

“…In table 7 [1], the authors reported F statistic values for various models fixed effects (time and treatment group). However, there are no parameters (intercept, beta coefficients or slopes) produced for fixed, interaction term: treatment x time or random effects.…”