Clinical correlates of non-responders to ketamine in terms of self-assessed life engagement among treatment-resistant depression patients.
TL;DR
Le non-response among TRD patients was associated with depression later onset, prior ECT, absence of diabetes, and occupational inactivity, and Pharmacological treatment alone may be insufficient to improve LE, underscoring the need to integrate psychosocial and behavioral interventions.
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.