Comparison of blinding effectiveness between sham tDCS and placebo sertraline in a 6-week major depression randomized clinical trial

Abstract

Objective: To compare blinding integrity and associated factors for transcranial direct current stimulation (tDCS) vs. placebo-pill, the gold standard blinding method.

Methods: Parallel trial. Depressed participants were randomized to verum/placebo sertraline and active/sham tDCS (2mA, 30-min 10-daily sessions and two additional, fortnight sessions) over 6weeks. Blinding was assessed in completers (n=102) and in a random subgroup (n=35) of raters and participants, in which we also inquired to qualitatively describe their strongest guessing reason.

Results: Participants and raters presented similar performance for predicting treatment assignment at endpoint, correctly guessing tDCS and sertraline beyond chance. Nevertheless, clinical response was associated with correct prediction and tDCS non-responders failed to predict the allocation group. For tDCS, "trouble concentrating" was inversely associated with correct prediction. "Skin redness" was more reported for active-tDCS, but did not predict the allocation group. The qualitative reasons for raters' guessing were not associated with correct prediction, whereas for participants clinical response and adverse effects were directly and inversely associated with correct prediction, respectively.

Conclusion: Blinding integrity of tDCS and sertraline were comparable and mainly associated with efficacy rather than blinding failure.

Significance: TDCS blinding can be improved by adopting parallel designs and avoiding subjects' awareness of skin redness.

Keywords: Clinical trial; Double-blind methods; Major depressive disorder; Placebo; Transcranial direct current stimulation.