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Distinct trajectories of response to prefrontal tDCS in major depression: results from a 3-arm randomized controlled trial


Transcranial direct current stimulation (tDCS) is a safe, effective treatment for major depressive disorder (MDD). While antidepressant effects are heterogeneous, no studies have investigated trajectories of tDCS response. We characterized distinct improvement trajectories and associated baseline characteristics for patients treated with prefrontal tDCS, an active pharmacotherapy (escitalopram), and placebo. This is a secondary analysis of a randomized, non-inferiority, double-blinded trial (ELECT-TDCS, N = 245). Participants were diagnosed with an acute unipolar, nonpsychotic, depressive episode, and presented Hamilton Depression Rating Scale (17-items, HAM-D) scores ≥17. Latent trajectory modeling was used to identify HAM-D response trajectories over a 10-week treatment. Top-down (hypothesis-driven) and bottom-up (data-driven) methods were employed to explore potential predictive features using, respectively, conservatively corrected regression models and a cross-validated stability ranking procedure combined with elastic net regularization. Three trajectory classes that were distinct in response speed and intensity (rapid, slow, and no/minimal improvement) were identified for escitalopram, tDCS, and placebo. Differences in response and remission rates were significant early for all groups. Depression severity, use of benzodiazepines, and age were associated with no/minimal improvement. No significant differences in trajectory assignment were found in tDCS vs. placebo comparisons (38.3, 34, and 27.6%; vs. 23.3, 43.3, and 33.3% for rapid, slow, and no/minimal trajectories, respectively). Additional features are suggested in bottom-up analyses. Summarily, groups treated with tDCS, escitalopram, and placebo differed in trajectory class distributions and baseline predictors of response. Our results might be relevant for designing further studies.

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Fig. 1: Distinct trajectories of change in depressive symptoms over 10 weeks of treatment with tDCS + placebo, escitalopram + sham tDCS, and placebo + sham tDCS.


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The authors thank Roberta Ferreira de Mello for administrative support.

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All authors have contributed substantially to the conception, data acquisition, analysis, or interpretation of data for the work; SG, FP, and ARB conceptualized the study, analyzed the data, and interpreted the results. LB and LBR were involved in data acquisition and interpretation of the findings. MB, NS, TSK, ZJD, and DMB were involved in the interpretation of the findings. All authors participated in the critical revision and finalization of the article and gave final approval for the version to be published.

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Correspondence to Andre R. Brunoni.

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Goerigk, S.A., Padberg, F., Bühner, M. et al. Distinct trajectories of response to prefrontal tDCS in major depression: results from a 3-arm randomized controlled trial. Neuropsychopharmacol. 46, 774–782 (2021).

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