Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression
Open accessAbstract
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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The lack of efficacy in this trial is likely due to the fact that most patients had mild to moderate depression as opposed to the more severe treatment-resistant major depression studied in ketamine clinical trials.
“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
Ketamine's antidepressant properties are transient, lasting an average of 1 week following a single infusion and 18-19 days following repeated infusions.
“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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“Although the studies evaluating ketamine are robust in showing the rapid improving of symptoms including suicidal ideation in TRD [99], the antidepressant effect of ketamine IV infusions is reported to last for around 2 weeks only [100,101].”
BackgroundA preliminary study of adjunctive ketamine for treatment-resistant bipolar depression
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Ketamine improves short-term plasticity in depression by enhancing sensitivity to prediction errors
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- 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 · 2012: 5
- 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 › 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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