Psilocybin in MDD
Trial question
What is the role of a single dose of psilocybin in patients with major depressive disorder?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
50.0% female
50.0% male
N = 104
104 patients (52 female, 52 male).
Inclusion criteria: adult patients aged 21-65 years with a DSM-5 diagnosis of major depressive disorder of ≥ 60 days of duration and moderate or greater symptom severity.
Key exclusion criteria: receiving antidepressants for ≥ 2 weeks; personal or first-degree family history of psychosis or mania; active substance use disorder; active suicidal ideation with intent.
Interventions
N=51 psilocybin (25 mg administered with psychological support).
N=53 placebo (niacin 100 mg administered with psychological support).
Primary outcome
Reduction in Montgomery-Asberg Depression Rating Scale score at day 43
19.1 points
6.8 points
19.1 points
14.3 points
9.6 points
4.8 points
0.0 points
Psilocybin
Placebo
Significant
increase ▲
Significantly greater reduction in Montgomery-Asberg Depression Rating Scale score at day 43 (19.1 points vs. 6.8 points; MD 12.3, 95% CI 7.2 to 17.5).
Secondary outcomes
Significantly greater reduction in Montgomery-Asberg Depression Rating Scale score at day 8 (17.8 points vs. 5.8 points; MD 12, 95% CI 7.4 to 16.6).
Significantly greater reduction in Sheehan Disability Scale score at day 43 (4.07 points vs. 1.76 points; MD 2.31, 95% CI 1.11 to 3.5).
Significant increase in sustained depressive symptom response (41.7% vs. 11.4%; AD 30.3%, 95% CI 13.5 to 47.1).
Conclusion
In adult patients aged 21-65 years with a DSM-5 diagnosis of major depressive disorder of ≥ 60 days of duration and moderate or greater symptom severity, psilocybin was superior to placebo with respect to reduction in Montgomery-Asberg Depression Rating Scale score at day 43.
Reference
Charles L Raison, Gerard Sanacora, Joshua Woolley et al. Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA. 2023 Sep 5;330(9):843-853.
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