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 and esketamine in treatment-resistant depression? A secondary analysis from a randomized controlled trial

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

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

Methods
This study is a secondary analysis from a bi-center, randomized, controlled trial. Participants were randomly assigned 1:1 to receive an IV infusion of esketamine (.25 mg/kg) or racemic ketamine (.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. The variation in depression scores was measured with the Montgomery-Asberg Depression Rating Scale (MADRS), which was administered before the intervention as a baseline measure and 24 hrs, 72 hrs, 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 (SD = 0.25; p-value 0.04) of predicted MADRS score from baseline to 24 hrs. The results for 72 hrs and 7 days following infusion were not significant. Limitations: This study was not designed to assess the relationship between ketamine or esketamine-induced dissociation and antidepressant effects as the main outcome, therefore confounding variables for this relationship were not controlled. 

Conclusions
We suggest a positive relationship between dissociation intensity, measured by CADSS, and antidepressant effect 24 hours after ketamine and esketamine infusion for a CADSS score of up to 15 points.


Submitted date:
11/17/2022

Accepted date:
09/01/2023

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