Ketamine, esketamine do not differ in cognitive effects for treatment-resistant depression

Ketamine and esketamine did not have different cognitive effects on individuals with treatment-resistant depression, according to study results published in Psychiatry Research.

“Despite the antidepressant efficacy of ketamine and esketamine in [individuals with treatment-resistant depression], there is still a relevant worry about their effect on cognition,” Lucas Araújo-de-Freitas, of the Laboratory of Neuropsychopharmacology at the Federal University of Bahia in Brazil, and colleagues wrote. “When used in higher doses, as an anesthetic substance or a recreational drug, ketamine leads to cognitive impairment. Two studies demonstrated that ketamine is associated with cognitive worsening even when used in antidepressant doses.”

However, most current findings showed no association between ketamine use for depression and impairment on cognition. To the researchers’ knowledge, no head-to-head study has compared the effects of antidepressant doses of ketamine or esketamine on cognition. Araújo-de-Freitas and colleagues sought to address this research gap by evaluating cognition among 54 patients with treatment-resistant depression before and after treatment with an infusion of either ketamine or esketamine and comparing potential differences in cognition linked to the two drugs. The researchers conducted assessments at baseline and 24 hours and 7 days after infusion. Further, they assessed executive functions, processing speed, short-term memory and auditory-verbal episodic memory via neuropsychological tests.

Results showed no cognitive difference between ketamine and esketamine, aside from for one variable related to visuospatial short-term and working memory. Ketamine and esketamine considered as one group did not impair cognition. Their use improved certain neuropsychological functions, such as visuospatial short-term memory, executive functions, processing speed and multiple measures related to episodic verbal memory.

“Our results suggesting improvement in different cognitive functions after treatment with subanesthetic doses of ketamine/esketamine are both clinically and scientifically relevant,” Araújo-de-Freitas and colleagues wrote. “Clinical implications of these drugs, due to their rapid antidepressant effect and potential procognitive effects, can reestablish functioning and quality of life. Future studies investigating the safety of long-term use of ketamine and esketamine on cognition are imperative.”