Single Ketamine Infusion and Neurocognitive Performance in Bipolar Depression
Abstract
We estimated neurocognitive performance using the trail making test (TMT) and the Stroop color-word interference test before, and on the 3(rd) day after a single infusion of ketamine, in 18 bipolar depressed patients receiving mood-stabilizing drugs. The performance on all tests significantly improved on the 3(rd) day after ketamine infusion which correlated positively with baseline intensity of neuropsychological impairment and was not associated either with baseline intensity of depression or reduction of depressive symptoms after 3 or 7 days. The results suggest that in such population of patients, single ketamine infusion may improve neuropsychological performance independently of antidepressant effect.
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In small, uncontrolled samples, convergent findings in depressed patients suggest cognitive flexibility on objective cognitive tests improves acutely following ketamine.
“In small, uncontrolled samples, convergent findings in depressed patients further suggest cognitive flexibility on objective cognitive tests improves acutely following ketamine 132,133 .”
From Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model (2020) · cites this paper as [133]
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“In small, uncontrolled samples, convergent findings in depressed patients further suggest cognitive flexibility on objective cognitive tests improves acutely following ketamine [132, 133].”
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“Therefore, it can be speculated that in this patient population, a single ketamine infusion may improve neuropsychological performance, independently of antidepressant effects (Permoda-Osip et al. 2015).”
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Papp, M., Gruca, P., Łasoń, M., & Willner, P. (2016) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000259 · Cited by 63 · see citing works
“…et al., 2015), but two recent studies have reported improvements in cognition, which appear to be independent of the antidepressant effects, 72 h following a single infusion of ketamine (Permoda-Osip et al., 2015) and in patients treated intermittently over a period of weeks (Lara et al., 2013).”
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“It was speculated that in such a population of patients, a single ketamine infusion may improve neuropsychological performance, independently of its antidepressant effect (Permoda-Osip et al. 2015).”
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“Moreover, one aspect of neuroprogression is cognitive dysfunction; currently, some evidence show that single and multiple ketamine infusions in subanaesthetic dose improve cognitive functions in patients with unipolar and bipolar depression.(119,120) Possible mechanisms of ketamine's action in bipolar disorder are pre…”
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“, 50% decrease in depressive measures from baseline) after three days [46].”
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“Racemic and S-ketamine were found to decrease cognitive symptoms [62] and increase cognitive performance [63, 64].”
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Fijtman, A., Yavi, M., Vogeley, A., Greenstein, D., Gilbert, J. R., & Zarate, C. A. (2025) · Bipolar Disorders · doi:10.1111/bdi.70027 · Cited by 3 · see citing works
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ResultKetamine: Its Safety, Tolerability, and Impact on Neurocognition
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Self-citationA half-century of participant observation in psychiatry. Part III: psychopharmacology.
Rybakowski, J. (2020) · Psychiatria Polska · doi:10.12740/pp/126249 · Cited by 2 · see citing works
Self-citationDonegan, K. R., Hossein, S., Panny, B., Brown, V. M., Lee, C. T., Harty, S., Lynch, K., Fox, C. A., Hanlon, A. K., O’Keane, V., et al. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03722-8 · Cited by 1 · see citing works
“In line with this, some preclinical and clinical studies have found improvements in cognitive fl exibility following ketamine administration, as indexed by performance in neurocognitive tests such as set-shifting task or Stroop interference test following the administration of ketamine [39 – 41].”
Kelly, C., Cooley, B. J., Zeng, L., Hurzeler, T. P., Manning, V., McNally, G. P., Watt, J., Haber, P., & Morley, K. C. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106911
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Chavigny, L.-A., Jodoin, V. D., Garel, N., Ndongo, M. S., Osborne, L., Turecki, G., & Richard-Devantoy, S. (2026) · Psychological Medicine · doi:10.1017/s0033291726103961
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Gębik, B., Bliźniewska-Kowalska, K. M., & Gałecki, P. (2025) · Psychiatria Polska · doi:10.12740/pp/onlinefirst/202128
“It is important to highlight that, in some patients, this effect occurs regardless of whether an antidepressant response is achieved or not [25].”
Mitchell, P. (2021) · Australian Family Physician · doi:10.1353/book.49280
Glutamate-based preclinical and clinical dysfunction and treatment in bipolar disorder
Decker, A., Bacalzo, B., & Niciu, M. J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821398-8.00020-5
Ketamine in Psychiatric Disorders
Danyeli, L. V., Götting, F. N., Şen, Z. D., Li, M., & Walter, M. (2021) · Springer eBooks · doi:10.1007/978-3-319-56015-1_420-1
Aleksandrova, L. R. (2019) · cIRcle (University of British Columbia) · doi:10.14288/1.0383291
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Mandolini, G., Lazzaretti, M., Altamura, A., & Brambilla, P. (2018) · Springer eBooks · doi:10.1007/978-3-319-75124-5_3
- Authors
- Permoda-Osip, A., Kisielewski, J., Bartkowska-Sniatkowska, A., & Rybakowski, J.
- Affiliations
- Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland
- Poznan University of Medical Sciences (PL)
- Department of Pediatric Anaesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Poznan, Poland
- Corresponding author
- Rybakowski, J.
- ORCID
- Rybakowski, J.
- Venue
- Pharmacopsychiatry
- Publisher
- Georg Thieme Verlag KG
- Published
- 2014-10-27
- Volume
- 48
- Issue
- 02
- Pages
- 78-79
- ISSN
- 0176-3679 (ISSN-L)
- 1439-0795
- OpenAlex
- W2080080993
- Cited by
- 40
- References
- 0
- Citations by year
- 2025: 2 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 9 · 2015: 1 · 2014: 1
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacopsychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- ketamine, single infusion, bipolar depression, neuropsychological performance, neuropsychological deficits, Trail Making Test, mood stabilizers, antidepressant effects
- MeSH terms
- Adult, Aged, Bipolar Disorder, Depression, Female, Humans, Infusions, Intravenous, Ketamine, Male, Middle Aged, Psychomotor Performance
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