Quality of Life in Patients with Treatment-Resistant Depression Treated with Intranasal Esketamine as Add-On Therapy to an SSRI—A Prospective, Comparative Study in Real-World Clinical Practice

Treatment-resistant depression (TRD) remains one of the most clinically challenging forms of depressive disorders. In many patients, reduction in symptom severity does not translate into full functional recovery; therefore, assessment of treatment effectiveness should also include health-related quality of life (HRQoL). Objective: The aim of the study was to compare changes in HRQoL in patients with TRD receiving a treatment strategy including intranasal esketamine as add-on therapy to ongoing treatment based on selective serotonin reuptake inhibitors (SSRIs) and in patients treated with SSRI-based therapy without esketamine. Materials and Methods: A prospective, observational, comparative cohort study was conducted in real-world clinical practice. Sixty adult patients were included: 30 received intranasal esketamine as add-on therapy to ongoing SSRI-based treatment and 30 received SSRI-based treatment without esketamine. The study protocol did not impose a separate SSRI dose-optimization algorithm; drug selection and dose modifications remained at the discretion of the treating physician in accordance with routine clinical practice. Quality of life was assessed using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) and the 36-Item Short Form Health Survey (SF-36). Depressive symptom severity was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HDRS). Assessments were performed at baseline, weeks 4, 8, and 12, and after 12 months. Results: Both groups showed improvement in quality of life and reduction in depressive symptom severity, with larger absolute changes in the group receiving esketamine. Differences involved WHOQOL-BREF domains and selected standard SF-36 subscales. Conclusions: In this observational cohort, the treatment strategy including intranasal esketamine was associated with greater improvement in several HRQoL measures than SSRI-based treatment without esketamine. Because treatment exposure was not assigned by the investigators and residual confounding cannot be excluded, the findings should not be interpreted as evidence of an isolated causal effect of esketamine.