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

• We compared blinding integrity of tDCS vs. placebo-pill in a 6-week, parallel, factorial randomized clinical trial in 102 patients with major depression.
• Participants correctly guessed tDCS and sertraline allocation groups beyond chance; nonetheless, it was mainly associated with clinical response and to a lesser extent with adverse effects.
• Although tDCS blinding is comparable to placebo-pill, further studies can improve it by designing parallel (vs. crossover) trials and avoiding subjects’ awareness of skin reddening, which more often occurs in the active arm.

ObjectiveTo compare blinding integrity and associated factors for transcranial direct current stimulation (tDCS) vs. placebo-pill, the gold standard blinding method.MethodsParallel trial. Depressed participants were randomized to verum/placebo sertraline and active/sham tDCS (2 mA, 30-min 10-daily sessions and two additional, fortnight sessions) over 6 weeks. 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.ResultsParticipants 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.ConclusionBlinding integrity of tDCS and sertraline were comparable and mainly associated with efficacy rather than blinding failure.SignificanceTDCS blinding can be improved by adopting parallel designs and avoiding subjects’ awareness of skin redness.