Effects of depression and melatonergic antidepressant treatment alone and in combination with sedative–hypnotics on heart rate variability: Implications for cardiovascular risk

Objectives: To examine heart rate variability (HRV) in unmedicated patients with major depressive disorder (MDD) and its changes after treatment with agomelatine alone and in combination with sedative–hypnotics. Methods: We recruited 152 physically healthy, unmedicated patients with MDD and 472 age- and sex-matched healthy volunteers. Frequency-domain measures of HRV were obtained during enrolment for all participants and again for MDD patients after 6 weeks of treatment with agomelatine alone and combining sedative–hypnotics. Results: Compared to the controls, unmedicated patients exhibited significantly lower mean R-R intervals, low-frequency (LF) HRV, and high-frequency (HF) HRV, but higher LF/HF ratios. Fifty-six and 49 patients successfully completed agomelatine monotherapy and the combination therapy of agomelatine and sedative–hypnotics, respectively. Between-group analyses showed significant treatment-by-group interactions for LF-HRV, HF-HRV and LF/HF ratio. The results showed a significant increase in HF-HRV after agomelatine monotherapy, a significant decrease in LF-HRV and HF-HRV, and a increase in the LF/HF ratio after combination therapy. Conclusions: MDD patients had reduced HRV, and the patterns of HRV changes differed between patients treated with agomelatine alone and in combination with sedative–hypnotics. Clinicians should consider HRV effects when adding sedative–hypnotics to agomelatine, which is important for depressed patients who already have decreased cardiac vagal tone.