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Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression
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Background Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusions resulted in a sustained antidepressant effect. In the current report, we examined the pattern and durability of antidepressant effects of repeated ketamine infusions in a larger sample, inclusive of the original. Methods Participants with TRD (n = 24) underwent a washout of antidepressant medication followed by a series of up to six IV infusions of ketamine (.5 mg/kg) administered open-label three times weekly over a 12-day period. Participants meeting response criteria were monitored for relapse for up to 83 days from the last infusion. Results The overall response rate at study end was 70.8%. There was a large mean decrease in Montgomery-Åsberg Depression Rating Scale score at 2 hours after the first ketamine infusion (18.9 ± 6.6, p < .001), and this decrease was largely sustained for the duration of the infusion period. Response at study end was strongly predicted by response at 4 hours (94% sensitive, 71% specific). Among responders, median time to relapse after the last ketamine infusion was 18 days. Conclusions Ketamine was associated with a rapid antidepressant effect in TRD that was predictive of a sustained effect. Future controlled studies will be required to identify strategies to maintain an antidepressant response among patients who benefit from a course of ketamine.
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“However, ketamine’s antidepressant properties are also transient, lasting an average of 1 week following a single infusion10–14 and 18–19 days following repeated infusions.15,16”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [15]
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“The lack of efficacy in our trial is likely due the fact that in our study most patients had mild to moderate depression as opposed to the more severe treatment-resistant major depression studied in ketamine clinical trials (Murrough et al, 2013a;Murrough et al, 2013b;Zarate et al, 2006).”
From Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial (2018) · cites this paper as Murrough et al, 2013b
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Metadata
- Authors
- Murrough, J. W., Perez, A. M., Pillemer, S., Stern, J., Parides, M. K., aan het Rot, M., Collins, K. A., Mathew, S. J., Charney, D. S., & Iosifescu, D. V.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Michael E. DeBakey VA Medical Center (US)
- Corresponding author
- Murrough, James W.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 74
- Issue
- 4
- Pages
- 250-256
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3725185
- OpenAlex
- W2091363925
- Cited by
- 786
- References
- 36
- Citations by year
- 2026: 29 · 2025: 49 · 2024: 40 · 2023: 56 · 2022: 68 · 2021: 70 · 2020: 91 · 2019: 59 · 2018: 56 · 2017: 45 · 2016: 66 · 2015: 65 · 2014: 52 · 2013: 31
- FWCI
- 35.99
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- National Institute of Mental Health (T32MH096678, R01MH081870, K23MH094707, 5R01MH81870)
- National Center for Research Resources (UL1RR029887)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- ketamine, rapid antidepressant effects, recurrence prediction, antidepressant response prediction
- MeSH terms
- Adult, Antidepressive Agents, Female, Humans, Infusions, Intravenous, Ketamine, Male, Middle Aged, Depressive Disorder, Treatment-Resistant
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