Trends in Psychiatry and Psychotherapy
http://www.trends.periodikos.com.br/article/doi/10.47626/2237-6089-2022-0593
Trends in Psychiatry and Psychotherapy
Original Article

Does the intensity of dissociation predict antidepressant effects 24 hours after infusion of racemic ketamine or esketamine in treatment-resistant depression? A secondary analysis from a randomized controlled trial

Mariana V. F. Echegaray, Rodrigo P. Mello, Guilherme M. Magnavita, Gustavo C. Leal, Fernanda S. Correia-Melo, Ana Paula Jesus-Nunes, Flávia Vieira, Igor D. Bandeira, Ana Teresa Caliman-Fontes, Manuela Telles, Lívia N. F. Guerreiro-Costa, Roberta Ferrari Marback, Breno Souza-Marques, Daniel H. Lins-Silva, Cassio Santos-Lima, Taiane de Azevedo Cardoso, Flávio Kapczinski, Acioly L. T. Lacerda, Lucas C. Quarantini

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Abstract

Objective
Ketamine and esketamine have both shown significant antidepressant effects in treatment-resistant depression (TRD) and conflicting evidence suggests that dissociation induced by these drugs could be a clinical predictor of esketamine/ketamine's efficacy.

Methods
This study is a secondary analysis of data from a two-center, randomized, controlled trial. Participants were randomly assigned 1:1 to receive an IV infusion of either esketamine (0.25 mg/kg) or racemic ketamine (0.50 mg/kg) over 40 minutes. Dissociative symptoms were assessed using the Clinician-Administered Dissociative State Scale (CADSS) 40 minutes following the beginning of the infusion. Variations in depression scores were measured with the Montgomery-Åsberg Depression Rating Scale (MADRS), which was administered before the intervention as a baseline measure and 24 hours, 72 hours, and 7 days following infusion.

Results
Sixty-one patients were included in the analysis. Examining CADSS scores of 15 or below, for every 1-point increment in the CADSS score, there was a mean change of −0.5 (standard deviation [SD] = 0.25; p = 0.04) of predicted MADRS score from baseline to 24 hours. The results for 72 hours and 7 days following infusion were not significant. Since the original trial was not designed to assess the relationship between ketamine or esketamine-induced dissociation and antidepressant effects as the main outcome, confounding variables for this relationship were not controlled.

Conclusion
We suggest a positive relationship between dissociation intensity measured with the CADSS and the antidepressant effects of ketamine and esketamine 24 hours after infusion for CADSS scores of up to 15 points.

Keywords

Ketamine; esketamine; treatment-resistant depression; major depressive disorder; dissociation

Submitted date:
11/17/2022

Accepted date:
09/01/2023

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