From Rhythm to Relief: Heart Rate Variability as a Window into Anhedonia Response During Agomelatine Treatment in Major Depressive Disorder

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. But little is known about the relationship between anhedonia improvement and HRV changes. This study aimed to investigate 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. After 8 weeks, SDNN levels in patients no longer differed significantly from HCs. SDNN decreased after one week of treatment but increased by week eight. Notably, a smaller reduction in SDNN after one week predicted greater improvement in anhedonia at week eight, filling the gap in the literature needed to facilitate treatment outcome prediction by integrating HRV assessment. Conclusions: Here we demonstrate that 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.