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Cited by 73Treatment of Major DepressionElectroconvulsive Therapy StudiesTranscranial Magnetic Stimulation Studies

Propofol for Treatment-Resistant Depression: A Pilot Study

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Mickey, Brian J, White, Andrea T, Arp, Anna M, Leonardi, Kolby, Torres, Marina M, Larson, Adam L, Odell, David H, Whittingham, Sara A +11 more·2018·International Journal of Neuropsychopharmacology
DOI 10.1093/ijnp/pyy085PMC PMC6276046
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Abstract

Background: We hypothesized that propofol, a unique general anesthetic that engages N-methyl-D-aspartate and gamma-aminobutyric acid receptors, has antidepressant properties. This open-label trial was designed to collect preliminary data regarding the feasibility, tolerability, and efficacy of deep propofol anesthesia for treatment-resistant depression. Methods: Ten participants with moderate-to-severe medication-resistant depression (age 18-45 years and otherwise healthy) each received a series of 10 propofol infusions. Propofol was dosed to strongly suppress electroencephalographic activity for 15 minutes. The primary depression outcome was the 24-item Hamilton Depression Rating Scale. Self-rated depression scores were compared with a group of 20 patients who received electroconvulsive therapy. Results: Propofol treatments were well tolerated by all subjects. No serious adverse events occurred. Montreal Cognitive Assessment scores remained stable. Hamilton scores decreased by a mean of 20 points (range 0-45 points), corresponding to a mean 58% improvement from baseline (range 0-100%). Six of the 10 subjects met the criteria for response (>50% improvement). Self-rated depression improved similarly in the propofol group and electroconvulsive therapy group. Five of the 6 propofol responders remained well for at least 3 months. In posthoc analyses, electroencephalographic measures predicted clinical response to propofol. Conclusions: These findings demonstrate that high-dose propofol treatment is feasible and well tolerated by individuals with treatment-resistant depression who are otherwise healthy. Propofol may trigger rapid, durable antidepressant effects similar to electroconvulsive therapy but with fewer side effects. Controlled studies are warranted to further evaluate propofol's antidepressant efficacy and mechanisms of action. ClinicalTrials.gov: NCT02935647.

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  • Several volatile anesthetics, such as isoflurane, nitrous oxide, propofol, and xenon, may produce rapid antidepressant effects.

    “Several volatile anesthetics, such as isoflurane, nitrous oxide, propofol, and xenon, may produce rapid antidepressant effects (157–165).”

    From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [162]

    The Discussion reports preliminary evidence that propofol may have antidepressant effects, and the Introduction cites evidence for isoflurane and nitrous oxide. But the Introduction explicitly calls propofol an intravenous anesthetic, not a volatile one, and our copy does not address xenon (searched: xenon). (LLM, conf=0.88)

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Cited by

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Authors
Mickey, B. J., White, A. T., Arp, A. M., Leonardi, K., Torres, M. M., Larson, A. L., Odell, D. H., Whittingham, S. A., Beck, M. M., Jessop, J. E., Sakata, D. J., Bushnell, L. A., Pierson, M. D., Solzbacher, D., Kendrick, E. J., Weeks, H. R., Light, A. R., Light, K. C., & Tadler, S. C.
Affiliations
University of Utah (US)
Corresponding author
Mickey, Brian J
ORCID
Venue
International Journal of Neuropsychopharmacology
Publisher
Oxford University Press (OUP)
Published
2018-09-27
Volume
21
Issue
12
Pages
1079-1089
ISSN
  • 1461-1457 (ISSN-L)
  • 1469-5111
DOI
10.1093/ijnp/pyy085
PMC
PMC6276046
OpenAlex
W2894063760
Cited by
73
References
9
Citations by year
2026: 7 · 2025: 11 · 2024: 12 · 2023: 11 · 2022: 7 · 2021: 9 · 2020: 10 · 2019: 6
FWCI
4.03
Type
journal article
Language
en
Open access
Licence
Locations
  • The International Journal of Neuropsychopharmacology (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institute of Mental Health (K23 MH092648)
  • Utah Center for Clinical and Translational Sciences (NCATS 8UL1TR000105, UL1RR025764)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
Keywords
propofol, treatment-resistant depression, antidepressant effects, electroconvulsive therapy, NMDA receptor, GABA receptors, treatment response prediction, tolerability
MeSH terms
Adolescent, Adult, Electroencephalography, Feasibility Studies, Female, Humans, Male, Middle Aged, Pilot Projects, Propofol, Outcome Assessment, Health Care, Anesthetics, Intravenous, Young Adult, Depressive Disorder, Treatment-Resistant

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