The association between anhedonia and quality of life in treatment-resistant depression: effects of a three-month treatment with esketamine nasal spray
I. Marcelli, M. Pepe, E. Specogna, A. Crupi, S. Barbonetti, L. Chisari, L. Balzoni, E. Stella, M. Lanzetta, M. Di Nicola, G. SaniIntroduction
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).