Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression
This open-label study (n=84) found that 6 ketamine (35mg/70kg) infusions over 12 days led to cognitive improvements (speed of processing, verbal learning) in those with depression. The improvements were mediated by the level of improvement in depressive symptoms. Those with a higher baseline of visual learning had the greatest antidepressant response.
Authors
- Yuping Ning
- Chengyu Wang
- Lujia Chen
Published
Abstract
Background
Ketamine has proven to have rapid, robust antidepressant effects on treatment-resistant depression. However, whether repeated ketamine infusions would cause short-and long-term neurocognitive impairments was not clear. Our aims were to investigate the neurocognitive effects of six ketamine infusions and to examine the association between these infusions and the antidepressant response in patients with unipolar and bipolar depression.
Methods
Six intravenous infusions of ketamine (0.5 mg/kg) over a 12-day period were administered to 84 patients with unipolar and bipolar depression. Severity of depressive symptoms and four domains of neurocognition, including speed of processing, working memory, visual learning and verbal learning, were assessed at baseline, one day following the last infusion and again two weeks post-infusion.
Results
Significant improvements were found on speed of processing (F=9.344, p<0.001) and verbal learning (F=5.647, p=0.004) in a linear mixed model. The Sobel test showed significant indirect effects between time and improvement in speed of processing (Sobel test=3.573, p<0.001) as well as improvement in verbal learning (Sobel test=6.649, p<0.001), which were both significantly mediated by change in depressive symptoms. Logistic regression analysis showed ketamine responders had better visual learning at baseline than non-responders (B=0.118, p<0.001).
Conclusions
Our findings suggest that neurocognitive function would not deteriorate after six ketamine infusions, while verbal learning and speed of processing improved over 13 days and 26 days of observation, respectively. However, this change was mainly accounted for by improvements in severity of depressive symptoms over time. Greater baseline visual learning predicted an antidepressant response over six ketamine infusion.
Research Summary of 'Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression'
Introduction
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist long used as an anaesthetic, has in recent decades been shown to produce rapid antidepressant effects in treatment-resistant depression (TRD) and to reduce suicidal thinking. A single subanesthetic intravenous infusion (0.5 mg/kg) produces robust but typically short-lived benefit, prompting increasing use of repeated infusions to prolong response. However, ketamine has also been associated with cognitive impairment in healthy volunteers and in chronic, heavy recreational users, raising concern about possible neurocognitive harms from repeated therapeutic infusions. Prior small studies in depressed samples produced inconsistent findings: some reported transient memory impairments immediately after single infusions, whereas others found no decline or even improvements after serial infusions, but sample sizes were limited. Zhou and colleagues set out to clarify two linked questions in a larger clinical sample: first, whether six serial subanesthetic ketamine infusions (0.5 mg/kg) over 12 days produce short-term neurocognitive changes during a 26-day observation period in patients with unipolar or bipolar depression; and second, whether baseline neurocognitive performance predicts antidepressant response to this six-infusion regimen. The authors hypothesised that six infusions would not produce lasting neurocognitive harm and that lower baseline cognition would predict a greater antidepressant response.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Zhou, Y., Zheng, W., Liu, W., Wang, C., Zhan, Y., Li, H., Chen, L., Li, M., & Ning, Y. (2018). Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression. Journal of Psychopharmacology, 32(10), 1118-1126. https://doi.org/10.1177/0269881118798614
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Zavaliangos-Petropulu, A., Mcclintock, S. M., Khalil, J. et al. · Journal of Affective Disorders (2023)
Wang, C., Lan, X-F., Zhou, Y. · Frontiers in Neuroscience (2023)
Albott, C. S., Lim, K. O., Erbes, C. et al. · Journal of Affective Disorders (2022)
Shiroma, P. R., Velit-Salazar, M. R., Vorobyov, Y. · Clinical Drug Investigation (2022)
Zhou, Y-L., Wang, C., Lan, X-F. et al. · Frontiers in Psychiatry (2022)
Zhou, Y-L., Wang, C., Lan, X-F. et al. · Journal of Psychiatric Research (2021)
Wilkowska, A., Szałach, L., Cubała, W. J. · Neuropsychiatric Disease And Treatment (2020)
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