Trends in Psychiatry and Psychotherapy
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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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. 

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.

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. 

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.

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