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Non-response to short-term ketamine use for treatment-resistant depression

Abstract

Background Ketamine is currently gaining attention as a rapid-acting antidepressant for treatment-resistant depression (TRD). However, many patients fail to respond, and limited data exist on predictors of non-response. This study aims to characterize the sociodemographic and clinical features associated with non-response to ketamine among TRD patients. Methods This is a post-hoc analysis of a naturalistic observational study, which enrolled 40 inpatients with treatment-resistant major depressive disorder and analyzed sociodemographic and clinical features in responders and non-responders stratified per Montgomery-Åsberg Depression Rating Scale (MADRS) during short-term ketamine administration (intravenous dosage: 0,5 mg/kg and orally: 2.0 or 2.5 mg/kg) that comprise over 4 weeks. Results In this study, 30 patients (75%) were classified as non-responders. No significant differences were detected among sociodemographic and clinical features beyond the history of substance use disorder (SUD) – only 53.3% of non-responders reported prior SUD (vs. 100%; p = 0.0075) and a lower number of psychiatric comorbidities (p = 0.0381). Conclusion This study highlights key characteristics of TRD non-responders to ketamine, including lower rates of SUD and fewer psychiatric comorbidities. These findings suggest that a higher burden of traditional TRD risk factors may not limit ketamine efficacy and could even enhance response compared to “pure” major depressive disorder. Identifying potential non-responders early can optimize treatment decisions, reduce ineffective exposure, and guide future research on improving TRD management.

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Category:
Articles
Type:
artykuły w czasopismach dostępnych w wersji elektronicznej [także online]
Published in:
Pharmacological Reports
ISSN: 1734-1140
Language:
English
Publication year:
2025
Bibliographic description:
Walaszek M., Cubała W. J., Kachlik Z., Pastuszak M., Pastuszak K., Kwaśny A., Non-response to short-term ketamine use for treatment-resistant depression, Pharmacological Reports, 2025,10.1007/s43440-025-00730-9
DOI:
Digital Object Identifier (open in new tab) 10.1007/s43440-025-00730-9
Sources of funding:
  • Po stronie autorów spoza PG
Verified by:
Gdańsk University of Technology

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