Cognitive outcomes following psilocybin-assisted therapy in treatment-resistant depression: A post-hoc analysis of a randomized, waitlist-controlled trial

BACKGROUND: Cognitive difficulties within treatment-resistant unipolar and bipolar depression (TRD; TRBD) often do not improve with conventional pharmacotherapies. Psilocybin-assisted psychotherapy (PAP) has shown promise as a novel intervention for TRD; however, few studies have assessed its effects on cognition in this population. METHODS: This retrospective post hoc analysis included 26 adults with TRD or TRBD from an open-label trial of PAP. Cognition was assessed with the Digit Symbol Substitution Test (DSST) and Trail Making Test Part A and B (TMT-A/B) at baseline, one-day, and two-weeks post-treatment. Linear mixed models (LMMs) evaluated change over time, and reliable change indices (RCIs) with binomial tests assessed whether the proportion of participants showing meaningful improvement exceeded chance. RESULTS: Significant improvements were observed on all cognitive measures over time (all p