Psilocybin vs. Escitalopram for Depression: A Landmark Comparison
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In one of the most influential clinical trials to date in psychedelic medicine, researchers at Imperial College London conducted a randomized, double-blind Phase 2 trial comparing psilocybin-assisted therapy to escitalopram (Lexapro), a commonly prescribed SSRI antidepressant.
This study, published in the New England Journal of Medicine in 2021 and led by Dr. Robin Carhart-Harris and Dr. David Nutt, sought to evaluate the safety and efficacy of psilocybin in treating moderate-to-severe major depressive disorder in a clinical population.
🧪 Study Design
• Participants: 59 adults diagnosed with major depressive disorder.
• Groups:
• One group received two high-dose psilocybin sessions (25 mg), spaced three weeks apart, plus a daily placebo for six weeks.
• The other group received two low-dose psilocybin sessions (1 mg—considered non-psychoactive) and daily escitalopram (10 mg, later increased to 20 mg).
• All participants received psychological support and therapy throughout.
📈 Key Findings
• Primary outcome: Both groups showed reductions in depression scores (measured by the QIDS-SR-16 scale), and the difference between groups did not reach statistical significance.
• Secondary outcomes: In several critical areas—including well-being, ability to feel pleasure, suicidal ideation, and emotional connection—the psilocybin group showed significantly greater improvement than the escitalopram group.
• 70% of participants in the psilocybin group showed clinically significant responses, compared to 48% in the SSRI group.
• Fewer side effects were reported with psilocybin than with escitalopram.
🧠 Interpretation
While the trial’s primary statistical benchmark was not met, the trend and secondary measures strongly favored psilocybin’s efficacy. This suggested that psilocybin may be at least as effective as SSRIs—and potentially more impactful for some people—especially in areas of emotional responsiveness and personal meaning.
The researchers emphasized the importance of set and setting, noting that the therapeutic context likely played a critical role in outcomes. Rather than being a drug to be taken daily, psilocybin is better viewed as a catalyst for therapeutic breakthroughs, often requiring only 1–2 sessions to yield lasting change.
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📖 Source & Read-Study Link
Title: Trial of Psilocybin versus Escitalopram for Depression
Authors: Robin Carhart-Harris et al.