title: Effects of depression and melatonergic antidepressant treatment alone and in combination with sedative-hypnotics on heart rate variability: Implications for cardiovascular risk.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: a 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: a Department of Psychiatry , Tri-Service General Hospital, National Defense Medical Center , Taipei , Taiwan.|b Student Counseling Center , National Defense Medical Center , Taipei , Taiwan.
authors.forename: Nian-Sheng
authors.initials: NS
authors.lastname: Tzeng
authors.affiliation: a Department of Psychiatry , Tri-Service General Hospital, National Defense Medical Center , Taipei , Taiwan.
authors.forename: Chin-Bin
authors.initials: CB
authors.lastname: Yeh
authors.affiliation: c Institute of Brain Science , National Yang-Ming University , Taipei , Taiwan.
authors.forename: Terry B J
authors.initials: TBJ
authors.lastname: Kuo
authors.affiliation: a 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: a Department of Psychiatry , Tri-Service General Hospital, National Defense Medical Center , Taipei , Taiwan.
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Chang
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D055815:Young Adult; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D006993:Hypnotics and Sedatives; C084711:agomelatine; D009281:Naphthalenes
keywords: Major depressive disorder; agomelatine; antidepressant; heart rate variability; sedative–hypnotics