Heart rate variability in major depressive disorder and after antidepressant treatment with agomelatine and paroxetine: Findings from the Taiwan Study of Depression and Anxiety (TAISDA)

Ta Chuan Yeh, Lien Cheng Kao, Nian Sheng Tzeng, Terry B.J. Kuo, San Yuan Huang, Chuan Chia Chang, Hsin An Chang

Research output: Contribution to journalArticle

27 Citations (Scopus)


Evidence from previous studies suggests that heart rate variability (HRV) is reduced in major depressive disorder (MDD). However, whether this reduction is attributable to the disorder per se or to medication, since antidepressants may also affect HRV, is still debated. There is a dearth of information regarding the effects of agomelatine, a novel antidepressant, on HRV. Here, we investigated whether HRV is reduced in MDD and compared the effects of agomelatine and paroxetine on HRV. We recruited 618 physically healthy unmedicated patients with MDD and 506 healthy volunteers aged 20-65. years. Frequency-domain measures of resting HRV were obtained at the time of enrollment for all participants. For patients with MDD, these measures were obtained again after 6. weeks of either agomelatine or paroxetine monotherapy. Compared with healthy subjects, unmedicated patients with MDD exhibited significantly lower variance (total HRV), low frequency (LF), and high frequency (HF) HRV, and a higher LF/HF ratio. Depression severity independently contributed to decreased HRV and vagal tone. Fifty-six patients completed the open-label trial (n. = 29 for agomelatine, n. = 27 for paroxetine). Between-group analyses showed a significant group-by-time interaction for LF-HRV and HF-HRV, driven by increases in LF-HRV and HF-HRV only after agomelatine treatment. Within the paroxetine-treated group, there were no significant changes in mean R-R intervals or any HRV indices. We therefore concluded that MDD is associated with reduced HRV, which is inversely related to depression severity. Compared with paroxetine, agomelatine has a more vagotonic effect, suggesting greater cardiovascular safety. Clinicians should consider HRV effects while selecting antidepressants especially for depressed patients who already have decreased cardiac vagal tone.

Original languageEnglish
Pages (from-to)60-67
Number of pages8
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Publication statusPublished - Jan 4 2016
Externally publishedYes



  • Agomelatine
  • Cardiac autonomic function
  • Heart rate variability
  • Major depressive disorder
  • Paroxetine

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

Cite this