Unmasking bias and MDMA-assisted therapy

Summary

The FDA rejected MDMA-assisted therapy for PTSD despite positive trial results, primarily due to concerns over unmasking bias. This study defines unmasking bias and calculates its magnitude for ketamine and escitalopram, finding that the bias is larger than the treatment effect size for MDMA. While the findings do not confirm that MDMA's effects are solely due to unmasking, they suggest that its effect sizes are not too large to be influenced by this bias.

Study at a glance

Abstract

On August 9th the US Food and Drug Administration’s (FDA) rejected 3,4-methylenedioxymethamphetamine assisted therapy (MDMA-AT) as a treatment for post-traumatic stress disorder (PTSD) despite seemingly positive trial results. A major reason cited was functional unmasking, which combined with enthusiasm about MDMA, raised concerns about the objectivity of these trials. Here, we define what is 'unmasking bias' and calculate its magnitude for two drugs, ketamine and escitalopram, where data was available from the literature. Our results show that unmasking bias for these two drugs is larger than the treatment vs. control effect size for MDMA. Our findings do not prove that effects of MDMA-AT are entirely or even partially due to unmasking, however, they indicate that MDMA-AT’s effect sizes are not too large to be due to unmasking.