title: 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).
abstract: 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.
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ta-Chuan
authors.initials: TC
authors.lastname: Yeh
authors.affiliation: Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Lien-Cheng
authors.initials: LC
authors.lastname: Kao
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Student Counseling Center, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Nian-Sheng
authors.initials: NS
authors.lastname: Tzeng
authors.affiliation: Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Terry B J
authors.initials: TB
authors.lastname: Kuo
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chuan-Chia
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Electronic address: chang.ha@mail.ndmctsgh.edu.tw.
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Chang
mesh_terms: D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D012146:Rest; D012720:Severity of Illness Index; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D002317:Cardiovascular Agents; D017374:Paroxetine; C084711:agomelatine; D009281:Naphthalenes
keywords: Agomelatine; Cardiac autonomic function; Heart rate variability; Major depressive disorder; Paroxetine