Trends in psychiatry and psychotherapySep 17, 2023

Does how strongly dissociation occurs predict antidepressant effects one day after ketamine or esketamine infusion in treatment-resistant depression?

Updated Jan 1, 2026

Abstract

In a study of 61 patients, a 1-point increase in dissociation scores was associated with a mean decrease of 0.5 in depression scores 24 hours after ketamine or esketamine infusion.

Dissociation was assessed using the Clinician-Administered Dissociative State Scale (CADSS) 40 minutes after drug infusion.
For CADSS scores of 15 or below, higher dissociation scores correlated with greater reductions in depression scores measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).
The relationship between dissociation intensity and antidepressant effects was only significant at the 24-hour mark, with no significant findings at 72 hours or 7 days.
Confounding variables affecting the relationship between dissociation and antidepressant effects were not controlled due to the study's design.

Simplified

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.

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Competing interests

Acioly L. T. Lacerda reports grants and personal fees from Janssen Pharmaceutical; personal fees from Daiichi Sankyo, Cristalia Produtos Químicos e Farmacêuticos, Libbs, Pfizer, Myralis Farma, Aché́ Laborató́rios, Hypera Pharma, and Sanofi-Aventis; grants from Eli Lilly, H. Lundbeck A/S, Servier Laboratories, Hoffman-La Roche, and Forum Pharmaceuticals. Lucas C. Quarantini reports consulting fees from Allergan, Abbott, Cristalia, Janssen Pharmaceutical, and Lundbeck; and research fees from Janssen Pharmaceutica. No other conflicts of interest declared concerning the publication of this article.

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