In a phase 2 trial of adults aged 21 to 65 years with major depressive disorder (MDD), treatment with psilocybin “was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events,” researchers report. “These findings add to increasing evidence that psilocybin—when administered with psychological support—may hold promise as a novel intervention for MDD.”
Conducted between Dec. 2019 and June 2022 at 11 research sites in the U.S., the study compared a single dose of psilocybin 25 mg vs. a niacin 100 mg placebo administered with psychological support. Participants had an MDD diagnosis for at least 60 days and moderate or greater symptom severity. Those with a history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent were excluded.
Based on a primary outcome of the change in central rater–assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43., the investigators found: “A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,−12.3 [95% CI, −17.5 to −7.2]; P <.001) and from baseline to day 8 (mean difference, −12.0 [95% CI, −16.6 to −7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, −2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent [adverse events (AEs)]; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs.”
Editorial: “Psychedelic therapies necessitate a rethinking of mental health care delivery in which medication is integrally paired with psychotherapy and delivered in a novel setting and framework,” editorialists write. “This will require an investment of time and resources, and it is not likely that these approaches will be broadly available to psychiatric patients except in clinical trials for the next few years. However, if the gains are strong and enduring and patients report symptom reduction and existential and spiritual transformation, the investment may be warranted. Meanwhile, clinicians should be knowledgeable about these new treatments as public interest and the empirical base grow.”