Heart Rate Variability as an Early Biomarker of Anhedonia Improvement During Agomelatine Treatment in Depression

Background and Objectives: Anhedonia, a core symptom of major depressive disorder (MDD), is a known predictor of treatment response. It has been linked to heart rate variability (HRV), a physiological marker implicated in both MDD and cardiovascular disease. Agomelatine, a melatonergic antidepressant, has shown positive effects on both anhedonia and HRV. This study investigated whether early changes in HRV predict anhedonia improvement following 8 weeks of agomelatine monotherapy. Materials and Methods: We enrolled 84 unmedicated patients with MDD and 143 age- and sex-matched healthy controls (HCs). Resting-state HRV, indexed by the standard deviation of NN intervals (SDNN), was recorded at baseline for all participants and after 1, 4, and 8 weeks of agomelatine treatment in patients. Anhedonia was assessed using the Snaith–Hamilton Pleasure Scale (SHAPS). Results: At baseline, patients exhibited significantly lower SDNN than HCs (U = -3.63, p < 0.001). After 8 weeks, SDNN levels in patients no longer differed significantly from HCs (U = -1.07, p = 0.29). SDNN decreased after one week of treatment (Z = -7.82, p = 0.026) but increased by week eight (Z = 3.60, p < 0.001). Notably, a smaller reduction in SDNN after one week predicted greater improvement in anhedonia at week eight (ρ = -0.25, p = 0.025). Conclusions: Early reductions in HRV may serve as a predictive biomarker for anhedonia response to agomelatine in MDD. These findings support the potential utility of HRV monitoring to guide personalized treatment strategies.