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 DOI: 10.47626/2237-6089-2022-0593 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Secondary analysis of a randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 61 |
| Population | Patients with treatment-resistant depression |
| Interventions | Esketamine Racemic ketamine |
| Dose | 0.25 mg/kg esketamine, 0.50 mg/kg racemic ketamine |
| Duration | Single 40-minute infusion, assessments at 24 hours, 72 hours, and 7 days |
| Topics | Depression Esketamine Ketamine |
| Keywords | Dissociation |
| Citations | 11 |
| Key findings | A positive relationship exists between dissociation intensity (up to a CADSS score of 15) and antidepressant effects of ketamine and esketamine at 24 hours after infusion, but not at later time points. |
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.