Psilocybin shows promising results in subjects continuing to use an antidepressant

Ongoing antidepressant treatment is believed to alter the psychedelic effect of psilocybin, so most psilocybin trials have required withdrawal from antidepressants before enrollment. There has been recent evidence, however, that administration of a selective serotonin reuptake inhibitor (SSRI) does not significantly alter the acute subjective effects of psilocybin. A Phase 2 open-label trial evaluated the safety and efficacy of a single dose of psilocybin with psychological support as adjunctive treatment to an SSRI in adults with treatment-resistant depression. Outpatients who met DSM-5 criteria for major depressive disorder and had experienced inadequate response to 2 to 4 antidepressant treatments in the current episode were eligible for inclusion. Participants received a single dose of psilocybin 25 mg during a 6- to 8-hour session accompanied by a therapist who did not actively guide participants. Up to three weeks of follow-up occurred in order to monitor safety and efficacy. Among the safety outcomes were incidence of adverse events, scores on laboratory tests, and change from baseline in suicidality. The primary efficacy outcome was change from baseline to 3 weeks post-administration in total score on the Montgomery-Asberg Depression Rating Scale (MADRS). Nineteen participants completed the study. Twelve participants experienced a total of 17 treatment-emergent adverse events, none of which were considered serious. No reports of active suicidal ideation occurred. Participants showed a clinically meaningful change from baseline on the primary efficacy measure, with improvement apparent by day 2 of the study. A total of 42.1% of participants achieved response as measured by the MADRS at week 3. Improvements in anxiety and quality of life were reported. [Goodwin, G., et al. (2023). Neuropsychopharmacol. https://doi.org/10.1038/s41386-023-01648-7]