“…Because investigators were not blinded to the time of randomization, this might suggest that the clinician-rated assessments (MADRS; CGI scales) may have been subject to some level of bias related to their awareness of when improvements could be expected. Although the patients were blinded to the placebo lead-in study feature, a similar pattern was observed for the patient-reported assessments (HADS scales; PGI), which might hypothetically be explained by ‘socially transmitted’ placebo effects ( Chen et al ., 2019 ), that is, investigators’ inadvertent and subconscious communication of their own expectations to the patient, and/or by patients not expecting an effect immediately after the first (placebo-) IV based on their previous experience or knowledge about antidepressant (SSRI) treatment. Altogether, such limitations may have led to reduced assay sensitivity, hence attenuating any treatment differences between vortioxetine and placebo, in this already small study.…”