Clinical correlates of anhedonia non-response to ketamine in treatment-resistant depression.
Michał Walaszek, Wiesław Jerzy Cubała, Zofia Kachlik, Michał Pastuszak, Krzysztof Pastuszak, Aleksander Kwaśny
Journal of Affective Disorders August 15, 2026 DOI: 10.1016/j.jad.2026.121762 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective analysis of naturalistic, observational registries Peer reviewed |
|---|---|
| Sample size | 34 |
| Population | Inpatients with treatment-resistant major depressive disorder |
| Intervention | Ketamine |
| Dose | IV: 0.5 mg/kg; oral: 2.0-2.5 mg/kg |
| Duration | Four weeks |
| Topics | Depression Ketamine Esketamine |
| Keywords | Anhedonia Psychopharmacology |
| Registration | NCT04226963 NCT05565352 |
| Key findings | Anhedonia non-response to short-term ketamine was associated with single marital status, fewer lifetime depressive episodes, and lower rates of substance use disorder. |
Abstract
Anhedonia, a core symptom of major depressive disorder (MDD), is associated with illness severity, suicide risk, poor functioning, and predicts poor response to antidepressants. While no treatments are approved, ketamine and esketamine show promise in reducing anhedonia. This study examines clinical and sociodemographic features linked to anhedonia treatment response in treatment-resistant depression (TRD) inpatients receiving short-term ketamine as an add-on to standard care. A retrospective analysis using data from naturalistic, observational registries of 34 inpatients with treatment-resistant major depressive disorder (NCT04226963 and NCT05565352). Patients received short-term ketamine (IV:0.5 mg/kg; oral:2.0-2.5 mg/kg) as add-on intervention over four weeks. Patients were stratified as responders or non-responders based on ≥50% Snaith-Hamilton Pleasure Scale (SHAPS) score reduction. Groups were compared on sociodemographic and clinical variables. 16 patients (47.1%) were non-responders. No significant differences were detected among sociodemographic and clinical features beyond the lower prior substance use disorder, fewer depressive episodes and differed in marital status. Non-responders were more prone to be single. A multivariable logistic regression model including these three predictors was globally significant (p = 0.024), with all predictors retaining consistent direction of association. The distribution of IV and oral ketamine administration was balanced between groups (p = 0.68). In this exploratory study, anhedonia non-response was associated with fewer lifetime depressive episodes, lower rates of substance use disorder, and single marital status. These characteristics underscore the demographic context of psychosocial factors in determining anhedonia treatment outcomes among ketamine non-responders and the importance of adopting a personalized approach to treatment in mood disorders.
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 |