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Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication.

Guy M. Goodwin, Megan Croal, David Feifel, John R. Kelly, Lindsey Marwood, Sunil Mistry, Veronica O'Keane, Stéphanie Knatz Peck, Hollie Simmons, Claudia Sisa, Susan C Stansfield, Joyce Tsai, Sam Williams, Ekaterina Malievskaia

Neuropsychopharmacology September 1, 2023 DOI: 10.1038/s41386-023-01648-7 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Open-label study Peer reviewed
Sample size 19
Population Adults with treatment-resistant depression
Intervention Psychological support
Dose 25 mg
Duration Single dose, 3-week follow-up
Topics Depression Psilocybin
Keywords Psychedelics Mental health Psilocybin therapy Antidepressants
Citations 166
Key points A single 25 mg dose of psilocybin adjunct to a selective serotonin reuptake inhibitor was associated with a mean 14.9-point reduction in depression severity at three weeks, with no serious adverse events.

Abstract

Psilocybin is being investigated as a treatment in adults with treatment-resistant depression (TRD). Withdrawal from serotonergic antidepressant drugs is a common prerequisite for taking part in trials of psilocybin due to the possibility of ongoing antidepressant drugs altering the psychedelic effect. This phase II, exploratory, international, fixed-dose, open-label study explored the safety, tolerability, and efficacy of a synthetic form of psilocybin (investigational drug COMP360) adjunct to a selective serotonin reuptake inhibitor in participants with TRD. Participants received a single 25 mg dose of psilocybin alongside psychological support and were followed-up for 3 weeks. The primary efficacy end point was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from Baseline at Week 3. Secondary end points were safety, including treatment-emergent adverse events (TEAEs), the proportion of responders and remitters at Week 3, and the change from Baseline to Week 3 in Clinical Global Impression-Severity (CGI-S) score. Nineteen participants were dosed and the mean Baseline MADRS total score was 31.7 (SD = 5.77). Twelve (63.2%) participants had a TEAE, most of which were mild and resolved on the day of onset. There were no serious TEAEs or indication of increased suicidal ideation or behavior. At Week 3, mean change from Baseline in MADRS total score was -14.9 (95% CI, -20.7 to -9.2), and -1.3 (SD = 1.29) in the CGI-S. Both response and remission were evident in 8 (42.1%) participants. Larger, comparator-controlled trials are necessary to understand if this paradigm can optimize treatment-outcome where antidepressant drug withdrawal would be problematic.

Comparable studies

Other non-randomized and open-label trials on psilocybin for depression, 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
Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Patients with treatment-resistant depression 2018 Clinical trial n = 20
Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Patients with major depressive disorder 2021 Open-label study n = 24
Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Individuals diagnosed with moderate to severe, treatment-resistant depression 2017 Open-label study n = 20

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