Measuring and appraising placebo effects in clinical trials: contemporary challenges and approaches in psychiatry.
Joseph J Taylor, Balázs Szigeti, Noah D Silverberg, Masoud Ahmadzad-Asl, Marina Kare, Ryan Webler, Diana K Orsini, Joshua D Rosenblat, Tom Bschor, Christopher Baethge, Mark Sinyor, Timothy R Nicholson, Tor D Wager, Matthew J Burke
The lancet. Psychiatry May 1, 2026 DOI: 10.1016/s2215-0366(26)00018-0 via PubMed
Summary
AI-generated from the abstractPlacebo effects remain a major paradox in medical research, with more data available from placebo-controlled trials than on any treatment, yet little deep analysis of how they are measured, appraised, and interpreted. This review shifts focus from clinical practice to clinical trials, examining established and emerging approaches for managing placebo effects in randomized controlled trials. It highlights three key challenges in contemporary psychiatric research: blinding and expectancy in psychedelic trials, large placebo responses in interventional psychiatry trials (device or procedure-based treatments), and the implications of overlapping neurobiological mechanisms between placebo effects and psychiatric treatments.
Study at a glance
| Characteristics | Review Randomized Placebo-controlled Peer reviewed |
|---|---|
| Key finding | Placebo effects pose major challenges in psychiatric clinical trials, particularly regarding blinding and expectancy in psychedelic trials, large placebo responses in device-based interventions, and overlapping neurobiological mechanisms with treatments. |
Abstract
Placebo effects are among the greatest paradoxes in medical research. Although more data on placebos are available from placebo-controlled trials than on any treatment in medicine, there has been comparatively little deep interrogation of issues related to their measurement, appraisal, and interpretation. Most of the work that has been done, including that in psychiatry, is narrowly focused on strategies for mitigating placebo effects and the challenges they might pose. In this Review, paper 2 of 2 on reconceptualising placebo and nocebo effects, we shift our focus from clinical practice to clinical trials. First, we review established and emerging approaches for navigating placebo effects in randomised controlled trials. Second, we examine three major challenges in contemporary psychiatric research that have recently highlighted the topic of placebo effects: (1) blinding and expectancy in psychedelic trials, (2) large placebo responses in interventional psychiatry trials (ie, device or procedure-based therapeutics), and (3) implications of overlapping neurobiological mechanisms between placebo effects and psychiatric treatments.