The potential pro-cognitive effects with intravenous subanesthetic ketamine in adults with treatment-resistant major depressive or bipolar disorders and suicidality
This single-blind, placebo-controlled study (n=111) assessed the cognitive effects of six ketamine infusions (35 mg/70 kg) in patients with unipolar or bipolar depression. Results indicate that ketamine improved processing speed independently of its antidepressant effects, while improvements in verbal learning were mediated by reductions in depressive symptoms.
Authors
- Roger McIntyre
- Yuping Ning
- Wei Zheng
Published
Abstract
Background
Ketamine has rapid and robust antidepressant effects in depression, while its effects on cognitive measures are less clearly understood. This aim of the study herein is to determine whether ketamine has direct pro-cognitive effects in real-world treatment depression and/or suicidality.
Methods
Subjects with unipolar (n = 84) and bipolar (n = 27) depression suffering treatment resistance or suicidality received six infusions of ketamine (0.5 mg/kg) during a 12-day period. Depression symptoms were assessed using the Montgomery-Asberg Depression Rating Scale at baseline, day 13 and day 26. Cognitive domains, including processing speed, working memory, visual learning and verbal learning were also measured using the MATRICS Consensus Cognitive Battery at the same time-points.ZhouResults: Significant improvement was observed in processing speed at day 13 (effect size [ES] = 0.501) and day 26 (ES = 0.654), and verbal learning at day 13 (ES = 0.362). Path analysis showed significant direct (β = 2.444, P = 0.017) and indirect (β = 1.220, P = 0.048) effect of ketamine on processing speed, indicating its improvement was partly independent of improvement in depressive symptoms. The direct effect (β = -1.963, P = 0.052) of ketamine on verbal learning was not significant, whereas the indirect effect (β = 1.386, P = 0.024) was significant, indicating treatment with ketamine indirectly improved verbal learning performance, via changes in depressive symptom.
Conclusion
Six infusions of ketamine have a potential mood independent pro-cognitive effect on processing speed in adults with treatment depression and/or suicidality. The potential pro-cognitive effects of ketamine provide the basis for hypothesizing that other clinical outcomes (e.g., suicidality, functional impairment) reported with ketamine treatment may be in part mediated by improvement in cognition.
Research Summary of 'The potential pro-cognitive effects with intravenous subanesthetic ketamine in adults with treatment-resistant major depressive or bipolar disorders and suicidality'
Introduction
Cognitive dysfunction is a central feature of mood disorders such as major depressive disorder (MDD) and bipolar disorder (BD), affecting attention, memory, learning, executive function and processing speed, and contributing to poor occupational and functional outcomes. Conventional antidepressants generally have limited or mood-mediated effects on cognition, and vortioxetine is the only agent with replicated evidence of direct pro-cognitive effects; by contrast, ketamine is established for rapid antidepressant and anti‑suicidal effects but its cognitive effects in clinical populations remain uncertain. Prior small and heterogeneous studies have suggested no severe persistent cognitive deficits following therapeutic ketamine and have raised the possibility of domain-specific improvements, but questions remain about whether any cognitive changes are independent of mood improvement or secondary to practice effects or sample characteristics. Zhou and colleagues set out to determine whether repeated, subanaesthetic intravenous ketamine produces direct pro‑cognitive effects in a large, real‑world sample of adults with treatment‑resistant or suicidal MDD or BD. The study aimed to assess changes across four cognitive domains (processing speed, working memory, visual learning and verbal learning) measured before treatment, 1 day after a six‑infusion course, and 14 days later, and to use mediation analysis to test whether cognitive changes were independent of reductions in depressive symptoms.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Zhou, Y., Wang, C., Lan, X., Zheng, W., Li, H., Chao, Z., Wu, K., McIntyre, R. S., & Ning, Y. (2021). The potential pro-cognitive effects with intravenous subanesthetic ketamine in adults with treatment-resistant major depressive or bipolar disorders and suicidality. Journal of Psychiatric Research, 144, 312-319. https://doi.org/10.1016/j.jpsychires.2021.10.037
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