Neurocognitive performance and serial intravenous subanesthetic ketamine in treatment-resistant depression
Open accessAbstract
The N-methyl-D-aspartate glutamate receptor antagonist ketamine has demonstrated rapid antidepressant effects in treatment-resistant depression (TRD). However, evaluation of ketamine's neurocognitive aspects in TRD has started to be explored. This study aims to (1) examine baseline neurocognitive performance and change in severity of depressive symptoms through six ketamine infusions, (2) examine the neurocognitive effects after completion of serial infusions and whether changes were associated to relapse to depression. Six IV infusions of 0.5 mg/Kg ketamine over 40 min were conducted on a Monday-Wednesday-Friday schedule during a 12-d period on 15 patients with TRD followed by a 4-wk observational period. Neurocognitive functioning was assessed using the CogState battery at baseline and at each follow-up visit. Tasks were designed to test attention, memory (working, visual, and verbal), speed of processing, and set shifting. The likelihood of response through six infusions was greater among depressed subjects with lower attention at baseline (F(1,13)=5.59, p=0.034). Significant improvement was found in scores of visual memory (F(4,33.82)=5.12, p=0.002), simple working memory (F(4, 24.85)=3.29, p=0.027) and complex working memory (F(4, 32.76)=4.18, p=0.008) after the last ketamine infusion. However, neurocognitive changes were accounted for by improvement in the severity of depressive symptom. The acute neurocognitive effect after completion of repeated infusions was not associated with the likelihood of subsequent relapse during follow-up. Our findings suggest a potential baseline neurocognitive predictor of ketamine response and the apparently lack of short-term neurocognitive impairment after completion of six ketamine infusions in TRD.
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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 [132]
The Results section ('Neurocognitive effects of six ketamine infusions'; page not provided) reports significant improvements in visual and working memory, but says all other cognitive tasks showed nonsignificant changes. The paper identifies set shifting as a tested domain, so it does not report an acute improvement in cognitive flexibility. (LLM, conf=0.85)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredImprovement in many domains of memory in another study of repeated infusions over 12 days with a 4 week follow-up was seen, but was not significant when controlling for depressive symptom improvement.
“Improvement in many domains of memory in another study of repeated infusions over 12 days with a 4 week follow-up period was seen, but was not significant when controlling for depressive symptom improvement.169”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [169]
Low attention and processing speed have been seen to be predictive of ketamine response.
“Low attention169 and processing speed have also been seen to be predictive.171”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [169]
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- Authors
- Shiroma, P. R., Albott, C. S., Johns, B., Thuras, P., Wels, J., & Lim, K. O.
- Affiliations
- University of Minnesota (US)
- Minneapolis VA Health Care System (US)
- Corresponding author
- Shiroma, Paulo R.
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-06-25
- Volume
- 17
- Issue
- 11
- Pages
- 1805-1813
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2120784916
- Cited by
- 126
- References
- 47
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 11 · 2023: 6 · 2022: 20 · 2021: 14 · 2020: 14 · 2019: 7 · 2018: 12 · 2017: 9 · 2016: 10 · 2015: 7 · 2014: 2
- FWCI
- 6.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- 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, treatment-resistant depression, neuropsychological performance, working memory, visual memory, attention, set-shifting, processing speed, depression relapse, antidepressant response prediction, NMDA receptor antagonists
- MeSH terms
- Adolescent, Adult, Aged, Anesthetics, Dissociative, Attention, Cognition, Depression, Female, Follow-Up Studies, Humans, Ketamine, Male, Memory, Middle Aged, Neuropsychological Tests, Psychiatric Status Rating Scales, Verbal Learning, Treatment Outcome, Young Adult
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