Commentary highlights that previous research had suggested that drug and placebo response rates in trials for depression, as well as other psychiatric disease, were rising, and that subsequently there had been significant investigation for modifying research design to account for diminishing relative placebo and drug responses (e.g. enrichment). This new evidence confirmed a previous historical trend of rising placebo responses, but found a “structural break” in 1991 after which no further increase of the placebo response was seen. Remaining questions are: what caused the increase of the placebo response observed before 1991? What initiated the “structural break” around the turn of the century? And why were these time trends and their change not observed in other medical subspecialties?