A Systematic Review of Neurocognitive Effects of Subanesthetic Doses of Intravenous Ketamine in Major Depressive Disorder, Post-Traumatic Stress Disorder, and Healthy Population
This paper (2022) reviews the neurocognitive effects of subanesthetic doses of intravenous ketamine in pharmacological studies among healthy subjects and patients with PTSD or depression. No significant impairment in cognitive function was found in patients with depression and possible in those with PTSD. In contrast, immediate cognitive dysfunction was found in healthy subjects.
Abstract
Background and Objective: Ketamine, a noncompetitive, high-affinity antagonist of the N-methyl-D-aspartate type glutamate receptor, has been investigated for its high efficacy and rapid antidepressant effect and, more recently, for its potential utility in post-traumatic stress disorder (PTSD). The proposal that ketamine’s antidepressant and anti-suicidal mechanism may be in part due to its procognitive effect contrasts with the well-established decreased performance on spatial working memory and pattern recognition memory among long-term frequent users. We aimed to review the neurocognitive effects of subanesthetic doses of intravenous ketamine in pharmacological studies among healthy subjects and patients with PTSD or depression.
Methods
We included studies in English, among healthy adults, or with PTSD or unipolar or bipolar depression where the primary or secondary cognitive outcomes were measured by means of a validated neuropsychological test. We excluded studies that reported the use of ketamine only in combination with other drugs or psychotherapy, or studies investigating emotion-laden cognitive functions.
Results
Ketamine administration among patients with depression and possibly with PTSD does not show significant impairment of cognitive functions in the short-term, in contrast with the immediate altered cognitive dysfunction found in healthy subjects. The potential procognitive effects of ketamine seem more pronounced in cognitive domains of executive function, which is in line with the putative molecular, cellular, and synaptic mechanisms of ketamine’s therapeutic action.
Conclusions
The potential procognitive effect of ketamine deserves further exploration. Whether ketamine has transient or sustained neurocognitive benefits beyond its antidepressant effects is unknown. Improved cognition by ketamine might be used to facilitate psychotherapy interventions for PTSD and depression.
Research Summary of 'A Systematic Review of Neurocognitive Effects of Subanesthetic Doses of Intravenous Ketamine in Major Depressive Disorder, Post-Traumatic Stress Disorder, and Healthy Population'
Introduction
Ketamine is a noncompetitive, high-affinity antagonist at the N-methyl-d-aspartate (NMDA) glutamate receptor that has attracted attention for its rapid antidepressant effects; its S-enantiomer, esketamine, is now FDA-approved for treatment-resistant depression. Shiroma and colleagues note ongoing safety concerns about cognitive effects at subanesthetic doses, set against evidence that longstanding, frequent recreational use is associated with impairments in spatial working memory and pattern recognition. Major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) themselves feature deficits across cognitive domains that can persist beyond mood symptom remission and may limit recovery and engagement with psychotherapies that require intact cognitive control and memory. This review therefore set out to summarise clinical trials that measured neurocognitive outcomes after subanesthetic intravenous (IV) ketamine in healthy subjects and in adults with PTSD or unipolar/bipolar depression. The investigators focused on ‘‘cold’’ cognitive domains (executive function, processing speed, learning and memory, attention/concentration) and excluded studies of emotion-laden or ‘‘hot’’ cognition, combination interventions, or non-validated cognitive measures.
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Shiroma, P. R., Velit-Salazar, M. R., & Vorobyov, Y. (2022). A Systematic Review of Neurocognitive Effects of Subanesthetic Doses of Intravenous Ketamine in Major Depressive Disorder, Post-Traumatic Stress Disorder, and Healthy Population. Clinical Drug Investigation, 42(7), 549-566. https://doi.org/10.1007/s40261-022-01169-z
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