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Cited by 187Psychedelics and Drug StudiesTreatment of Major DepressionTranscranial Magnetic Stimulation Studies

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

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Goodwin, Guy M., Croal, Megan, Feifel, David, Kelly, John R., Marwood, Lindsey, Mistry, Sunil, O’Keane, Veronica, Peck, Stephanie Knatz +6 more·2023·Neuropsychopharmacology
DOI 10.1038/s41386-023-01648-7PMC PMC10425429
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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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  • A previous study of 19 patients who did not wish to taper off of their SSRIs before psilocybin-assisted therapy reported no negative effects on safety, though it was an uncontrolled study.

    “A previous study of 19 patients who did not wish to taper off of their SSRIs before psilocybin-assisted therapy also reported no negative effects on safety, though it was an uncontrolled study (Goodwin et al., 2023).”

    From Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response (2024) · cites this paper as Goodwin et al., 2023

    The Results (Participants) report that 19 patients received psilocybin while continuing SSRIs. The Discussion describes a generally favorable safety profile and confirms that the study was open-label and had no comparator. But Materials and methods (Participants) says patients were considered if they were unable or unwilling to withdraw medication, or preferred this study; it does not establish that all 19 did not wish to taper. (LLM, conf=0.87)

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Cited by

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Authors
Goodwin, G. M., Croal, M., Feifel, D., Kelly, J. R., Marwood, L., Mistry, S., O’Keane, V., Peck, S. K., Simmons, H., Sisa, C., Stansfield, S. C., Tsai, J., Williams, S., & Malievskaia, E.
Affiliations
  • Tallaght University Hospital (IE)
  • University of California San Diego (US)
Corresponding author
Goodwin, Guy M.
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2023-07-13
Volume
48
Issue
10
Pages
1492-1499
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/s41386-023-01648-7
PMC
PMC10425429
OpenAlex
W4384130479
Cited by
187
References
14
Citations by year
2026: 53 · 2025: 64 · 2024: 64 · 2023: 6
FWCI
47.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropsychopharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Oxford University Research Archive (ORA) (University of Oxford) (publishedVersion)
Funders
COMPASS Pathfinder Ltd
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
Keywords
psilocybin, treatment-resistant depression, selective serotonin reuptake inhibitors, antidepressant discontinuation, adjunctive therapy, psychedelic therapy, depression severity, treatment-emergent adverse events, suicidal ideation
MeSH terms
Adult, Antidepressive Agents, Major Depressive Disorder, Double-Blind Method, Humans, Psilocybin, Treatment Outcome, Depressive Disorder, Treatment-Resistant

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