Cognitive effects of intravenous Ketamine in treatment-resistant depression: A systematic review.
Lou-anne Chavigny, Véronique Desbeaumes Jodoin, Nicolas Garel, Manola Sob Ndongo, Laura Osborne, Gustavo Turecki, Stéphane Richard Devantoy
Psychological medicine May 8, 2026 Peer reviewed DOI: 10.1017/s0033291726103961 via PubMed
Summary
Intravenous low-dose ketamine appears to preserve and enhance cognitive functions in patients with treatment-resistant depression, particularly in processing speed, working memory, and executive control. No cognitive deterioration was reported, and the procognitive effects may be linked to ketamine's potential to reduce suicidal thoughts. The review analyzed 21 studies involving approximately 900-1,180 participants, highlighting improvements in attention and variability in memory results.
Study at a glance
| Design | systematic review |
|---|---|
| Sample size | 1,000 |
| Population | patients with treatment-resistant depression |
| Key finding | Subanesthetic IV ketamine enhances specific cognitive functions in treatment-resistant depression without causing cognitive deterioration. |
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.