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
Trends in Psychiatry and Psychotherapy May 27, 2025 Peer reviewed DOI: 10.47626/2237-6089-2022-0593 via DOAJ
Summary
A positive relationship was suggested between the intensity of dissociation and the antidepressant effects of ketamine and esketamine in patients with treatment-resistant depression, specifically for dissociative scores of 15 or below. For each 1-point increase in dissociative symptoms measured at 40 minutes post-infusion, there was a corresponding mean decrease of 0.5 in depression scores after 24 hours. However, no significant results were observed at 72 hours or 7 days.
Study at a glance
| Design | randomized controlled trial |
|---|---|
| Sample size | 61 |
| Population | patients with treatment-resistant depression |
| Key finding | A positive relationship was suggested between dissociation intensity and antidepressant effects of ketamine and esketamine at 24 hours post-infusion for CADSS scores of up to 15. |
Abstract
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.