Psilocybin shows promising results in subjects continuing to use an antidepressant
The Brown University Psychopharmacology Update October 4, 2023 DOI: 10.1002/pu.31089 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label Phase 2 trial Peer reviewed |
|---|---|
| Sample size | 19 |
| Population | Outpatients with DSM-5 major depressive disorder and inadequate response to 2 to 4 antidepressant treatments in the current episode, concurrently taking an SSRI |
| Intervention | Psilocybin |
| Dose | 25 mg |
| Duration | Single 6- to 8-hour session; up to 3 weeks of follow-up |
| Measures | Montgomery–Asberg Depression Rating Scale (MADRS) |
| Topics | Psilocybin |
| Key findings | A single 25 mg psilocybin dose given with psychological support alongside ongoing SSRI treatment produced clinically meaningful MADRS improvement by day 2, with 42.1% of 19 participants meeting response criteria at week 3. Adverse events were reported by 12 participants (17 events total), none serious, and no active suicidal ideation occurred. |
Abstract
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]
Comparable studies
Other non-randomized and open-label trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Patients with moderate-to-severe, unipolar, treatment-resistant major depression | 2016 | Open-label feasibility trial | n = 12 |
| Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Patients with severe, unipolar, treatment-resistant major depression | 2017 | Open-label trial | n = 20 |
| Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Psychiatrically healthy nicotine-dependent smokers | 2014 | Open-label pilot study | n = 15 |
| Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Patients with treatment-resistant depression | 2018 | Clinical trial | n = 20 |
| Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder Subjects with obsessive-compulsive disorder (OCD) | 2006 | Controlled clinical trial |