Reconceptualization of Drug Effects in Double Blind Randomized Placebo Controlled Trials for Psychiatric Illnesses: A Practical Suggestion

Double blind randomized placebo controlled trials (RCTs) have been regarded as the gold standard for evaluation of potential treatments. Nevertheless RCTs for psychiatric illnesses, almost all of which sorely need better medications, have been plagued with high placebo response, practically diluting true drug effects (if any) and potentially discouraging novel drug developments. Various strategies have been considered to tackle this significant issue but none has been particularly successful to date. The author proposes to examine the belief of treatment allocation by the study participants, (at least) twice, during the study period. The results will be interpreted in terms of correctness and consistency, regardless of the actual treatment allocation. Whether response trajectory differs based on these parameters (e.g., robust placebo response stems from those who consistently guessed placebo as active drug) should be tested and analyzed. The concept could be useful regarding functional unblinding, another serious issue in psychiatric RCTs, for drugs with strong clinical effects.