Relationship Between Dissociation and Antidepressant Effects of Esketamine Nasal Spray in Patients With Treatment-Resistant Depression.
Antidepressant
dissociation
esketamine
treatment-resistant depression
Journal
The international journal of neuropsychopharmacology
ISSN: 1469-5111
Titre abrégé: Int J Neuropsychopharmacol
Pays: England
ID NLM: 9815893
Informations de publication
Date de publication:
19 04 2022
19 04 2022
Historique:
received:
19
03
2021
revised:
16
09
2021
accepted:
04
01
2022
pubmed:
14
1
2022
medline:
22
4
2022
entrez:
13
1
2022
Statut:
ppublish
Résumé
In this post-hoc analysis, data from 2 positive, pivotal, phase 3 trials of esketamine nasal spray (ESK) in treatment-resistant depression (TRD)-short-term study (TRANSFORM-2) and maintenance study (SUSTAIN-1)-were analyzed to evaluate the relationship between dissociation and antidepressant effects of ESK. Analysis by responder status, correlation analysis, and mediation analysis were performed to assess the relationships between peak Clinician Administered Dissociative States Scale (CADSS) scores after first (day 1) and last (day 25) ESK dose and change in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores at the first (day 2) and last assessments (day 28) in TRANSFORM-2 and peak CADSS after first maintenance ESK dose and time to relapse in SUSTAIN-1 (only for mediation analysis). In TRANSFORM-2, the percentage of responders (>50% reduction in MADRS) at day 2 and day 28 did not significantly differ between patients who did vs did not manifest significant dissociation (peak CADSS scores >4 or ≤4, respectively) following the first ESK dose. Spearman correlation coefficients between dissociation and depression improvement were nonsignificant and close to zero. CADSS scores did not significantly mediate the reduction in MADRS at day 2 or 28 in TRANSFORM-2 or the time to depression relapse in SUSTAIN-1. The mean difference in MADRS between ESK and active-control arms persisted beyond day 2 without significant change across time, although the mean peak CADSS scores significantly decreased across consecutive doses and fewer patients experienced significant dissociation after the last ESK dose compared with the first. Within the dose range tested, the dissociative and antidepressant effects of ESK were not significantly correlated. NCT02417064 (TRANSFORM-1); NCT02418585(TRANSFORM-2); NCT02493868 (SUSTAIN-1).
Sections du résumé
BACKGROUND
In this post-hoc analysis, data from 2 positive, pivotal, phase 3 trials of esketamine nasal spray (ESK) in treatment-resistant depression (TRD)-short-term study (TRANSFORM-2) and maintenance study (SUSTAIN-1)-were analyzed to evaluate the relationship between dissociation and antidepressant effects of ESK.
METHODS
Analysis by responder status, correlation analysis, and mediation analysis were performed to assess the relationships between peak Clinician Administered Dissociative States Scale (CADSS) scores after first (day 1) and last (day 25) ESK dose and change in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores at the first (day 2) and last assessments (day 28) in TRANSFORM-2 and peak CADSS after first maintenance ESK dose and time to relapse in SUSTAIN-1 (only for mediation analysis).
RESULTS
In TRANSFORM-2, the percentage of responders (>50% reduction in MADRS) at day 2 and day 28 did not significantly differ between patients who did vs did not manifest significant dissociation (peak CADSS scores >4 or ≤4, respectively) following the first ESK dose. Spearman correlation coefficients between dissociation and depression improvement were nonsignificant and close to zero. CADSS scores did not significantly mediate the reduction in MADRS at day 2 or 28 in TRANSFORM-2 or the time to depression relapse in SUSTAIN-1. The mean difference in MADRS between ESK and active-control arms persisted beyond day 2 without significant change across time, although the mean peak CADSS scores significantly decreased across consecutive doses and fewer patients experienced significant dissociation after the last ESK dose compared with the first.
CONCLUSION
Within the dose range tested, the dissociative and antidepressant effects of ESK were not significantly correlated.
TRIAL REGISTRATION
NCT02417064 (TRANSFORM-1); NCT02418585(TRANSFORM-2); NCT02493868 (SUSTAIN-1).
Identifiants
pubmed: 35022754
pii: 6504017
doi: 10.1093/ijnp/pyab084
pmc: PMC9017766
doi:
Substances chimiques
Antidepressive Agents
0
Nasal Sprays
0
Esketamine
50LFG02TXD
Ketamine
690G0D6V8H
Banques de données
ClinicalTrials.gov
['NCT02418585', 'NCT02417064', 'NCT02493868']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
269-279Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.
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