Cognitive Effects of Ketamine in Mood Disorders
Summary
Ketamine, an NMDA receptor antagonist, has emerged as a rapid-acting intervention for major depressive disorder and related mood disorders. Beyond its antidepressant and antisuicidal effects, growing interest has centred on its cognitive profile. At subanesthetic doses, single intravenous or intranasal administrations can transiently impair domains such as attention, executive function and verbal memory, typically resolving within 24 hours. Conversely, repeated low-dose regimens—particularly with esketamine—appear not only benign in terms of cognitive side effects but may enhance processing speed and certain memory functions in vulnerable populations. Preclinical models link these outcomes to synaptic modulation in the hippocampus, where ketamine restores long-term potentiation and NMDA receptor–mediated transmission, and regulates AMPA receptor trafficking. Understanding this duality between acute cognitive disruption and longer-term synaptic plasticity is crucial for optimising therapeutic protocols and mitigating risks in clinical practice.
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Cognitive Effects of Ketamine in Mood Disorders publication trend
The graph below shows the total number of articles in cognitive effects of ketamine in mood disorders across all publications each year (not limited to Nature Index journals).
Technical terms
Subanesthetic dose: A ketamine dose below that required to induce general anaesthesia, typically used to achieve antidepressant effects with minimal dissociative symptoms.
Processing speed: The rate at which an individual can perceive, interpret and respond to information, often measured by timed tasks.
Working memory: A cognitive system responsible for temporarily holding and manipulating information during complex tasks.
Long-term potentiation (LTP): A long-lasting enhancement in synaptic strength following high-frequency stimulation, considered a cellular correlate of learning and memory.
NMDA receptor (NMDAR): A subtype of glutamate receptor that plays a central role in synaptic plasticity and memory formation.
References
- Short-term cognitive effects of repeated-dose esketamine in adolescents with major depressive disorder and suicidal ideation: a randomized controlled trial. Child and Adolescent Psychiatry and Mental Health (2023).
- Acute cognitive effects of single-dose intravenous ketamine in major depressive and posttraumatic stress disorder. Translational Psychiatry (2021).
- Effect of Ketamine on LTP and NMDAR EPSC in Hippocampus of the Chronic Social Defeat Stress Mice Model of Depression. Frontiers in Behavioral Neuroscience (2018).
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