Clinical correlates of non-responders to ketamine in terms of self-assessed life engagement among treatment-resistant depression patients.
J Psychiatr Res September 10, 2026 DOI: 10.1016/j.jpsychires.2026.09.003 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective observational analysis Peer reviewed |
|---|---|
| Sample size | 65 |
| Population | Inpatients with treatment-resistant major depressive disorder or bipolar depression |
| Intervention | Ketamine |
| Dose | IV: 0.5 mg/kg; oral: 2.0-2.5 mg/kg |
| Duration | Four weeks |
| Measures | Inventory of Depressive Symptomatology Self-Report (IDS-SR) 10 LE score |
| Topics | Depression Esketamine Ketamine |
| Registration | NCT04226963 NCT05565352 |
| Key findings | About half of patients (33 of 65, 50.8%) did not respond on the life engagement measure after short-term ketamine. Non-response was associated with later depression onset, prior ECT, absence of diabetes, and occupational inactivity; the authors state these findings are preliminary and suggest pharmacological treatment alone may be insufficient to improve life engagement. |
Abstract
Background: Major depressive and bipolar disorders are leading causes of disability, with many patients developing treatment-resistant depression (TRD/TRBD). Ketamine offers rapid symptom relief, yet recovery extends beyond symptoms. Life engagement (LE) is a key patient-centered outcome encompassing the ability to experience pleasure, function effectively, and participate in meaningful activities but remains understudied. This study examines clinical and sociodemographic correlates of LE non-response following short-term ketamine intervention.
Methods: A retrospective analysis using data from naturalistic, observational registries of 65 inpatients with treatment-resistant major depressive disorder or bipolar depression (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% Inventory of Depressive Symptomatology Self-Report (IDS-SR) 10 LE score reduction. Groups were compared on sociodemographic and clinical variables.
Results: 33 patients (50.8%) were classified as non-responders. Sociodemographic and baseline clinical variables were similar between groups. Non-responders had later depression onset (39.5 vs 24.5 years; p = 0.0257), more frequent prior ECT (40% vs 9.4%; p = 0.0084), no comorbid diabetes (vs 21.9%; p = 0.0048), and differed in employment status (p = 0.0171). These findings are preliminary and require confirmation in larger samples.
Conclusions: In this post-hoc analysis LE non-response among TRD patients was associated with depression later onset, prior ECT, absence of diabetes, and occupational inactivity. This may reflect greater illness severity, psychosocial burden, and a lack of potential neuroplasticity enhancement through metabolic pharmacotherapy. Pharmacological treatment alone may be insufficient to improve LE, underscoring the need to integrate psychosocial and behavioral interventions.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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The abstract does not report results; the study concerns clinical correlates of non-response to ketamine in terms of self-assessed life engagement.
Synthesized
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 |