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

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...

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Main Authors: 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
Format: Article
Language:English
Published: Associação de Psiquiatria do Rio Grande do Sul 2025-05-01
Series:Trends in Psychiatry and Psychotherapy
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Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2237-60892025000100505&lng=en&tlng=en
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author 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
author_facet 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
author_sort Mariana V. F. Echegaray
collection DOAJ
description 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.
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spelling doaj-art-0884ef21c9454794bd931f09d4da4b782025-08-20T02:29:04ZengAssociação de Psiquiatria do Rio Grande do SulTrends in Psychiatry and Psychotherapy2238-00192025-05-014710.47626/2237-6089-2022-0593Does 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 trialMariana V. F. Echegarayhttps://orcid.org/0000-0002-4891-2354Rodrigo P. Mellohttps://orcid.org/0000-0002-1809-088XGuilherme M. Magnavitahttps://orcid.org/0000-0002-2577-9896Gustavo C. Lealhttps://orcid.org/0000-0001-5447-025XFernanda S. Correia-Melohttps://orcid.org/0000-0002-0954-6590Ana Paula Jesus-Nuneshttps://orcid.org/0000-0002-0389-1940Flávia Vieirahttps://orcid.org/0000-0001-5987-2450Igor D. Bandeirahttps://orcid.org/0000-0002-6714-2658Ana Teresa Caliman-Fonteshttps://orcid.org/0000-0003-4675-5268Manuela TellesLívia N. F. Guerreiro-Costahttps://orcid.org/0000-0002-2367-0870Roberta Ferrari Marbackhttps://orcid.org/0000-0003-3870-8963Breno Souza-Marqueshttps://orcid.org/0000-0002-3431-7888Daniel H. Lins-SilvaCassio Santos-Limahttps://orcid.org/0000-0002-7685-9829Taiane de Azevedo Cardosohttps://orcid.org/0000-0003-1925-8709Flávio Kapczinskihttps://orcid.org/0000-0001-8738-856XAcioly L. T. Lacerdahttps://orcid.org/0000-0002-9370-0449Lucas C. Quarantinihttps://orcid.org/0000-0002-8807-8464Abstract 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2237-60892025000100505&lng=en&tlng=enKetamineesketaminetreatment-resistant depressionmajor depressive disorderdissociation
spellingShingle 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
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
Trends in Psychiatry and Psychotherapy
Ketamine
esketamine
treatment-resistant depression
major depressive disorder
dissociation
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Ketamine
esketamine
treatment-resistant depression
major depressive disorder
dissociation
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2237-60892025000100505&lng=en&tlng=en
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