A Systematic Review of Neurocognitive Effects of Subanesthetic Doses of Intravenous Ketamine in Major Depressive Disorder, Post-Traumatic Stress Disorder, and Healthy Population

• Published in: Clinical drug investigation Vol. 42; no. 7; pp. 549 - 566
• Main Authors: Shiroma, Paulo R., Velit-Salazar, Mario Renato, Vorobyov, Yelena
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-07-2022; Springer Nature B.V
• Subjects: Antidepressants; Cognition & reasoning; Drug dosages; Executive function; Internal Medicine; Ketamine; Medicine; Medicine & Public Health; Memory; Mental depression; Neuropsychology; Pattern recognition; Pharmacology/Toxicology; Pharmacotherapy; Post traumatic stress disorder; Psychotherapy; Psychotropic drugs; Semantics; Systematic Review; United States > US
• ISSN: 1173-2563; 1179-1918
• DOI: 10.1007/s40261-022-01169-z

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 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.