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

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...

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Main Authors: 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
Format: Article
Language:English
Published: Associação de Psiquiatria do Rio Grande do Sul 2025-05-01
Series:Trends in Psychiatry and Psychotherapy
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Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2237-60892025000100505&lng=en&tlng=en
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Summary: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.
ISSN:2238-0019