Non-response to short-term ketamine use for treatment-resistant depression.
Pharmacological reports : PR – April 30, 2025
Source: PubMed
Summary
While ketamine offers hope for severe mood disorders, new findings reveal surprising patterns in treatment response. Among patients with treatment-resistant depression, those with fewer psychiatric complications were actually less likely to benefit from ketamine therapy. This challenges traditional assumptions in psychopharmacology, suggesting that complex cases may respond better to ketamine than those with "pure" depression.
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.