Psy-Q: Are ketamine and esketamine cognitively safe in subanesthetic doses to manage treatment-resistant depression (TRD)? Lucas Quarantini MD, PhD, answers.

Dr Quarantini

Lucas Quarantini MD, PhD

Dr Araújo de Freitas

Lucas Araújo de Freitas MD, PhD

Answer: Yes, and both ketamine and esketamine were shown to improve cognition after 24 hours and 7 days later, according to a study by Araújo de Freitas et al. The team assessed the cognitive effects of ketamine and esketamine for treating 54 patients with treatment-resistant depression (TRD) and found that the drugs provided similar improvements some neuropsychological functions such as visuospatial short-term memory, executive functions, processing speed, and several measures related to episodic verbal memory. Lucas Araújo de Freitas MD, PhD, a professor of psychiatry at the Universidade Federal da Bahia (UFBA) in Salvador, Brazil, and the paper’s corresponding author, Lucas Quarantini MD, PhD, professor of psychiatry and principal investigator at the Laboratory of Neuropsychopharmacology at the UFBA, discussed their team’s findings with Psycom Pro.

Low Doses of Ketamine for Treatment-Resistant Depression

Psycom Pro: Your team’s study was the first to examine low doses of ketamine and esketamine in a head-to-head comparison for their effects on cognition in people with TRD. Were your findings surprising to you and your team?

Dr. Quarantini: Yes, definitely. There is a vast amount of evidence available in the literature that recreational use of ketamine poses a relevant risk of cognitive impairment. On the other hand, since we used low doses of ketamine and esketamine, there was an expectation that there could be an improvement in cognition following the improvement achieved in the mood analysis. However, the possibility of an improvement in cognition beyond the improvement of antidepressant effects surprised us.

Ketamine and Cognition

Psycom Pro: How do your team’s findings that ketamine and esketamine can improve cognition for people in TRD help to advance the acceptance and more mainstream use of these as a treatment?

Dr. Araújo de Freitas: This is an important question. Ketamine is used as a recreational drug in high doses and studies show that, in this case, cognition is worsened acutely and chronically. Our study suggests, however, that ketamine and esketamine are cognitively safe in antidepressant doses and purpose. Other studies with more ketamine/esketamine infusions also point to this direction. We hope that our study contributes to the acceptance of ketamine and esketamine as a safe and effective option for TRD.

Psycom Pro: What is important for psychiatrists and prescribing clinicians to understand about your ketamine study results?

Dr. Araújo de Freitas: Most importantly, ketamine and esketamine improve mood and cognition quickly in people with TDR. We have few options to treat depression with quick results, and ketamine and esketamine should be considered. However, in some countries, like Brazil, we still don’t have intranasal esketamine, and we don’t have more ketamine available—there is only esketamine for parenteral use. Therefore, the results of this study provide evidence of efficacy and safety that can support the clinical use of these molecules.

Dr. Quarantini: We hope that future studies conducted by other groups can replicate the results of our study. Finally, we want to have more long-term safety studies available for the cognitive functions of adolescents and adults treated with different forms of ketamine.

More perspectives on ketamine and esketamine for treatment-resistant depression.

Last Updated: Sep 9, 2021