Cognitive effects of intravenous Ketamine in treatment-resistant depression: A systematic review

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: Not reported in abstract

• Primary Outcome: Procognitive effects observed across multiple domains, particularly processing speed, working memory, and executive control

• Nnt Or Sensitivity: Not applicable - systematic review of cognitive outcomes

• Confidence Interval: Not reported in abstract

Clinical Application

High - IV ketamine is established treatment in specialized psychiatric settings with appropriate monitoring Highly relevant - IV ketamine (Spravato/esketamine) is TGA-approved for treatment-resistant depression. Results support cognitive safety profile important for Australian prescribers and patients concerned about cognitive side effects Adults with treatment-resistant depression considering IV ketamine therapy

Abstract

Intravenous (IV) low-dose ketamine has emerged as a promising treatment for patients with treatment-resistant depression (TRD). However, its impact on cognitive functioning remains unclear. This systematic review examines the cognitive and executive effects of IV ketamine in TRD, focusing on their relationship to depressive and suicidal outcomes. A systematic search of Cochrane, MEDLINE, Embase, and PsycINFO databases was conducted up to May 15, 2025, using the terms depression, cognition, and ketamine. This review was conducted in accordance with the PRISMA guidelines, and the protocol was registered in PROSPERO (ID: 1160487). Risk of bias was evaluated using the Cochrane RoB 2 tool for randomized trials and the ROBINS-I tool for non-randomized studies. Twenty-one studies, comprising approximately 900-1,180 participants with TRD, assessed cognitive domains of processing speed, working memory, attention, verbal and visual memory, cognitive flexibility, and executive control. Procognitive effects were frequently observed in processing speed and working memory, while attention results were preserved or modestly improved, and verbal and visual memory results were heterogeneous. Executive control, particularly inhibitory performance on Stroop paradigms, improved in several trials. Two studies directly examined cognition as it relates to suicidal behaviors. No cognitive deterioration was reported. Subanesthetic IV ketamine appears to preserve and enhance specific cognitive functions in TRD, notably across processing speed, working memory, and executive control. These procognitive effects, particularly in executive control, may mediate ketamine's antisuicidal action. Standardized longitudinal studies are warranted to clarify their durability and clinical significance.

References

1. 1.Chavigny, L. A., Desbeaumes Jodoin, V., Garel, N., Sob Ndongo, M., Osborne, L., Turecki, G., & Richard Devantoy, S. (2026). Cognitive effects of intravenous Ketamine in treatment-resistant depression: A systematic review. Psychological Medicine. https://doi.org/10.1017/S0033291726103961