Neurocognitive aspects of ketamine and esketamine on subjects with treatment-resistant depression: A comparative, randomized and double-blind study

This randomized, double-blind, placebo-controlled study (n=54) finds that both esketamine and (racemic) ketamine improve cognition immediately and up to 7 days later for those suffering from depression (TRD). There were virtually no differences between both subgroups. The study found improvements in executive functions, processing speed, and more.


The objective of this study is to evaluate cognition in patients using either ketamine or esketamine to treat TRD. We also evaluate if both ketamine and esketamine as one group influence cognition in patients with TRD. Fifty-four patients with TRD were infused with either ketamine or esketamine and were assessed at three time points: baseline, 24 h, and 7 days after infusion. We applied neuropsychological tests to evaluate executive functions, processing speed, short term memory, and auditory-verbal episodic memory. There is no cognitive difference between ketamine and esketamine, with the exception of one variable. When considered as one group, ketamine and esketamine do not impair cognition; on the contrary, they improve some neuropsychological functions such as visuospatial short-term memory, executive functions, processing speed, and several measures related to episodic verbal memory. Ketamine and esketamine do not present differing cognitive effects when used in antidepressant doses to treat TRD. Furthermore, they rapidly improve many cognitive aspects of patients with TRD at 24 h after the infusion and maintain these effects for at least 7 days.

Authors: Lucas Araújo-de-Freitas, Cassio Santos-Lima, Euclides Mendonça-Filho, Flávia Vieira, Ricardo J. A. F. França, Guilherme Magnavita, Tanise L. Cardoso, Fernanda S. Correia-Melo, Gustavo C. Leal, Ana P. Jesus-Nunes, Breno Souza-Marques, Roberta Marback, Manuela Teles, Mariana Vf. Echegaray, Graziele Beanes, Lívia N. F. Guerreiro-Costa, Rodrigo P. Mello, Thaís Rabanea, Ana C. Lucchese, Neander Abreu, Acioly L. T. Lacerda & Lucas C. Quarantini

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Study characteristics
Placebo-Controlled Double-Blind Randomized