EPV564
The association between anhedonia and quality of life in treatment-resistant depression: effects of a three-month treatment with esketamine nasal spray
I. Marcelli 1,*, M. Pepe 2, E. Specogna 1, A. Crupi 1, S. Barbonetti 1, L. Chisari 1, L. Balzoni 1, E. Stella 1, M. Lanzetta 1, M. Di Nicola 1 2, G. Sani 1 2
1Department of Neuroscience, Section of Psychiatry, Università Cattolica del Sacro Cuore, 2Department of Psychiatry, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy
Introduction: Anhedonia is a core and frequently treatment-refractory symptom dimension of treatment-resistant depression (TRD), strongly associated with functional impairment and reduced quality of life. Esketamine nasal spray (ESK-NS) has demonstrated anti-anhedonic effects in real-world clinical settings; however, the extent to which improvement in anhedonia contributes to functional and quality-of-life recovery remains insufficiently explored.
Objectives: This study examined changes in depressive symptoms, anhedonia, and quality of life in TRD patients treated with ESK-NS for three months. In addition, we investigated whether reductions in anhedonia mediate the association between improvements in depressive symptoms and quality of life.
Methods: Fifty patients with TRD (36.3% female; mean age 54.7±12.4 years) receiving ESK-NS for three months were retrospectively included. Depression severity was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Beck Depression Inventory-II (BDI-II). Anhedonia was evaluated using the anhedonia subscales of the MADRS and BDI-II. Quality of life was measured with the EuroQol-5 Dimensions (EQ-5D). Statistical analyses included descriptive measures (mean ± SD, percentages), repeated-measures ANOVA, and mediation analysis, with significance set at p<0.05.
Results: ESK-NS significantly improved depressive symptoms over the treatment period (MADRS, p=0.006; BDI-II, p=0.002). Anhedonia significantly decreased according to MADRS anhedonia scores (p=0.04), while BDI-II anhedonia scores showed marked improvement at the endpoint (p<0.001). Quality of life improved significantly following three months of treatment (p<0.001). Mediation analysis demonstrated that reductions in anhedonia significantly mediated the relationship between depressive symptom improvement and enhanced quality of life (Figure 1).
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Conclusions: Three-month treatment with ESK-NS significantly improved depressive symptoms, anhedonia, and quality of life in TRD patients. Interestingly, reductions in anhedonia emerged as a key mediator linking clinical improvement to quality of life. These findings underscore the relevance of anhedonia as a central therapeutic target in TRD, highlighting the importance of assessing both symptomatic and quality-of-life outcomes in clinical practice.
Disclosure of Interest: None Declared