Ketamine, Sleep, and Depression: Current Status and New Questions
Open accessAbstract
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has well-described rapid antidepressant effects in clinical studies of individuals with treatment-resistant major depressive disorder (MDD). Preclinical studies investigating the effects of ketamine on brain-derived neurotrophic factor (BDNF) and on sleep slow wave activity (SWA) support its use as a prototype for investigating the neuroplastic mechanisms presumably involved in the mechanism of rapidly acting antidepressants. This review discusses human EEG slow wave sleep parameters and plasma BDNF as central and peripheral surrogate markers of plasticity, and their use in assessing ketamine's effects. Acutely, ketamine elevates BDNF levels, as well as early night SWA and high-amplitude slow waves; each of these measures correlates with change in mood in depressed patients who respond to ketamine. The slow wave effects are limited to the first night post-infusion, suggesting that their increase is part of an early cascade of events triggering improved mood. Increased total sleep and decreased waking occur during the first and second night post infusion, suggesting that these measures are associated with the enduring treatment response observed with ketamine.
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The increase in SWA correlates strongly with increases in synaptic plasticity and plasma BDNF preclinically and in ketamine-responsive MDD patients.
“This increase in SWA correlates strongly with increases in synaptic plasticity and plasma BDNF preclinically,135 and in ketamine-responsive MDD patients.113,133”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [133]
Ketamine has well-described effects on increasing total sleep and slow-wave sleep/slow-wave activity, and its antidepressant response has been linked to this effect.
“Ketamine has well-described effects on increasing total sleep and slow-wave sleep/slow-wave activity (SWS/SWA),133 and its antidepressant response has been linked to this effect.113”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [133]
Improvement in SWS/SWA may be unique to patients with unipolar depression; ketamine responders with bipolar depression were found to experience a reduction of SWA.
“Interestingly, this improvement in SWS/SWA may be unique to patients with unipolar depression. Ketamine responders with bipolar depression were found to experience the opposite effect – that is, a reduction of SWA.”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [133]
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- Authors
- Duncan, W. C., & Zarate, C. A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Zarate, Carlos A.
- ORCID
- Zarate, Carlos A.
- Venue
- Current Psychiatry Reports
- Published
- 2013-08-16
- Volume
- 15
- Issue
- 9
- Pages
- 394-394
- ISSN
- 1523-3812 (ISSN-L)
- 1535-1645
- PMC
- PMC3827949
- OpenAlex
- W2092088903
- Cited by
- 76
- References
- 60
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 3 · 2023: 7 · 2022: 4 · 2021: 12 · 2020: 9 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 7 · 2015: 5 · 2014: 2
- FWCI
- 0.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Current Psychiatry Reports (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (ZIAMH002857, ZIAMH002927)
- 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
- ketamine, major depressive disorder, treatment-resistant depression, rapid-acting antidepressants, NMDA receptor antagonism, brain-derived neurotrophic factor, slow-wave sleep, neuroplasticity, EEG, plasma BDNF, sleep duration, antidepressant response
- MeSH terms
- Depressive Disorder, Electroencephalography, Humans, Sleep Initiation and Maintenance Disorders, Ketamine, Biomarkers, Excitatory Amino Acid Antagonists, Brain-Derived Neurotrophic Factor
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