Beyond SSRIs: Psilocybin in Treatment-Resistant Depression & What It Means for Substance Use Disorders

Can psilocybin help patients with treatment-resistant depression and what does the latest clinical evidence mean for people dealing with both depression and addiction? In this episode of The Transformed Minds (Host Rx), psychiatrist Dr. O breaks down a landmark 2022 NEJM phase II randomized, double-blind, multicenter trial examining psilocybin therapy for treatment-resistant depression (TRD).Dr. O explains what qualifies as TRD, walks through the trial's three-arm dosing design (1 mg, 10 mg, and 25 mg plus structured psychological support), and interprets the primary outcome, MADRS score change at three weeks. The 25 mg dose showed statistically significant and clinically meaningful improvement, but the story gets more complex by week 12.This episode is especially valuable for clinicians, patients, and advocates navigating dual diagnosis care co-occurring depression and substance use disorders. Dr. O covers:- psilocybin-assisted therapy- treatment-resistant depression, - MADRS depression scale, - psychedelic safety- mental health equity- substance use disorder and depressionWhether you're a mental health professional, someone living with TRD, or simply following the rapidly evolving conversation around psychedelic medicine, this episode gives you the evidence-based framework to think critically, not just hopefully about what psilocybin can and cannot do right now.