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, Stephane Richard-Devantoy
Psychological Medicine May 8, 2026 DOI: 10.1017/s0033291726103961 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Longitudinal Peer reviewed |
|---|---|
| Population | Patients with treatment-resistant depression |
| Topics | Depression Ketamine Esketamine |
| Keywords | Executive function Processing speed Suicidal cognition |
| Key findings | Subanesthetic intravenous ketamine preserves and enhances specific cognitive functions in treatment-resistant depression, particularly processing speed, working memory, and executive control, with no cognitive deterioration reported. |
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.
Comparable studies
Other systematic reviews and meta-analyses on ketamine for depression, most cited first.