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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 Esketamine |
| Keywords | Mood disorders Psychopharmacology Treatment non-response Ketamine therapy Psychiatric comorbidity |
| Citations | 3 |
| Key findings | 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.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
| Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... | 2017 | Observational cohort | n = 59 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |