Non-response to short-term ketamine use for treatment-resistant depression.
Michał Walaszek, Wiesław Jerzy Cubała, Zofia Kachlik, Michał Pastuszak, Krzysztof Pastuszak, Aleksander Kwaśny
Pharmacological reports : PR April 30, 2025 DOI: 10.1007/s43440-025-00730-9 via PubMed
Summary
AI-generated from the abstractAmong inpatients with treatment-resistant depression receiving ketamine over four weeks, 75% did not respond. Non-responders had lower rates of prior substance use disorder (53.3% vs. 100%) and fewer psychiatric comorbidities. The findings suggest that a higher burden of traditional risk factors for treatment-resistant depression may not limit ketamine's effectiveness and could even enhance response compared to 'pure' major depressive disorder. Early identification of potential non-responders could optimize treatment decisions and reduce ineffective exposure.
Study at a glance
| Characteristics | Post-hoc analysis of a naturalistic observational study Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | Inpatients with treatment-resistant major depressive disorder |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg intravenously and 2.0 or 2.5 mg/kg orally |
| Duration | 4 weeks |
| Topics | Depression Ketamine |
| Keywords | Mood disorders Psychopharmacology Treatment non-response Ketamine therapy |
| Citations | 3 |
| Key finding | 75% of patients were non-responders to ketamine, and non-responders had lower rates of prior substance use disorder and fewer psychiatric comorbidities. |
Abstract
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. 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. 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). 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.