Unique Psychological Mechanisms Underlying Psilocybin Therapy Versus Escitalopram Treatment in the Treatment of Major Depressive Disorder
Carhart-Harris, R. L., Erritzoe, D., Giribaldi, B., Nutt, D. J., Roseman, L., Weiss, B.
This secondary of a trial (n=59) investigates the mechanisms underlying the efficacy of Psilocybin Therapy (PAT) versus Escitalopram Treatment in patients with depression (MDD) over a 6-week trial period. Acute psychological experiences such as mystical experience and ego dissolution were found to mediate the effect of treatment condition on depressive response, suggesting a mechanistic role of these experiences in the treatment of depression via PAT.
Abstract
The mechanisms by which Psilocybin Therapy (PT) improves depression remain an important object of study, with scientists actively exploring acute psychological experiences and neurobiological processes as candidates. In a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we investigated whether acute psychological experiences could meaningfully account for the unique efficacy of PT versus Escitalopram Treatment over a core 6-week trial period. An exploratory-factor-analysis-derived single-factor of depression was used as the outcome. Among a comprehensive set of acute experiences related to psilocybin, so-called “mystical experience” and “ego dissolution” were unique in mediating the effect of treatment condition on depressive response with high specificity. Higher reported levels of mystical experience, emotional breakthrough, and intense responses to music-listening were furthermore associated with greater antidepressant response. These results provide qualified support for the causal mechanistic role of acute psychological experiences in the treatment of depression via PT.