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Clinical Trial
. 2023 Sep;48(10):1492-1499.
doi: 10.1038/s41386-023-01648-7. Epub 2023 Jul 13.

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

Guy M Goodwin  1 , Megan Croal  2 , David Feifel  3 , John R Kelly  4 , Lindsey Marwood  2 , Sunil Mistry  2 , Veronica O'Keane  4 , Stephanie Knatz Peck  5 , Hollie Simmons  2 , Claudia Sisa  2 , Susan C Stansfield  2 , Joyce Tsai  2 , Sam Williams  2 , Ekaterina Malievskaia  2
Affiliations
Clinical Trial

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

Guy M Goodwin et al. Neuropsychopharmacology. 2023 Sep.

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.

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Conflict of interest statement

A contract research organization (Worldwide Clinical Trials), paid by the sponsor, supervised the conduct of the trial under the direction of the sponsor. An independent contract research organization (Worldwide Clinical Trials) were responsible for conducting MADRS assessments with blinded remote raters. The analysis of the data was performed by the contract research organization (Worldwide Clinical Trials); and the interpretation of the data was performed by the sponsor. GMG has consulted for Beckley Psytech, Boehringer Ingelheim, Clerkenwell Health, EVApharm, H Lundbeck A/S, Janssen Global Services, Novartis, Ocean Neurosciences, P1vital, Sage Therapeutics, Servier, Takeda and WebMD. GMG, MC, LM, SM, HS, CS, SCS, JT, SW, and EM are current or past employees of COMPASS Pathfinder. GMG, MC, LM, SM, HS, CS, JT, SW, and EM own shares or options in COMPASS Pathfinder. DF has received grant funding from MindMed, Neurolief, Perception Neuroscience, and Relmada Therapeutics. DF holds a patent for psychedelic drug treatment of neuropsychiatric disorders and cerebral palsy. DF, JRK, VOK, and SK-P were site investigators or sub-investigators for COMPASS Pathfinder during the clinical trial and received funding to conduct the study, and SK-P is a consultant for COMPASS Pathfinder, providing therapist training and mentorship, and clinical development. JRK has consulted for Clerkenwell Health and has received grant funding from the Health Research Board (ILP-POR-2022-030).

Figures

Fig. 1
Fig. 1. Change from baseline in MADRS total score (full analysis set).
CI confidence interval, MADRS Montgomery-Åsberg depression rating scale, SD standard deviation, SSRI selective serotonin reuptake inhibitor. Note: Baseline mean (SD): COMP360 25 mg + SSRI = 31.7 (5.77).
Fig. 2
Fig. 2. Change from baseline in CGI-S score and proportion of CGI-S responders over time (full analysis set).
CGI-S Clinical Global Impressions – Severity, CI confidence interval, SSRI selective serotonin reuptake inhibitor. Number of CGI-S responders stated in bars. Note: Mean change from Baseline CGI-S score was −1.3 at Week 3.
Fig. 3
Fig. 3
Summary of 5D-ASC Dimension Scores on Day 1 (full analysis set).
See this image and copyright information in PMC

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