Acute effects of ketamine and esketamine on cognition in healthy subjects: A meta-analysis

Impairment in cognition is frequently associated with acute ketamine administration. However, some questions remain unanswered as to which deficits are most prominent and what variables modulate these effects.

A literature search yielded 56 experimental studies of acute ketamine administration that assessed cognition in 1041 healthy volunteers. A multivariate meta-analysis was performed, and effect sizes were estimated for eleven cognitive domains: attention, executive function, response inhibition, social cognition, speed of processing, verbal / language, verbal learning, verbal memory, visual learning & memory, visuospatial abilities, and working memory.

There were small-to-moderate impairments across all cognitive domains. Deficits in verbal learning / memory were most prominent, whereas response inhibition was the least affected. Meta-regression analysis revealed that the negative effects of ketamine on cognition are dependent on infusion dose and plasma level, but unaffected by enantiomer type, route of administration, sex or age. A publication bias was observed.

Acute ketamine broadly impairs cognition across all domains among healthy individuals. Verbal learning and memory figures most prominently in cognitive impairment elicited by acute ketamine administration.