Longitudinal evidence for unfavorable effects of antidepressants on heart rate variability

Biol Psychiatry. 2010 Nov 1;68(9):861-8. doi: 10.1016/j.biopsych.2010.06.032. Epub 2010 Sep 16.


Background: It was previously shown that antidepressants are associated with diminished vagal control over the heart. Longitudinal studies are needed to test the causality of this association further.

Methods: Longitudinal data were obtained in the Netherlands Study of Depression and Anxiety. At baseline and at 2-year follow-up, heart rate and cardiac vagal control as indexed by respiratory sinus arrhythmia were measured in 2114 subjects (mean age = 42.0 years; 66.2% female), who either used antidepressants at one or two time points (n = 603) or did not use antidepressants at any time point (n = 1511). Linear mixed-model analyses were conducted to compare changes in respiratory sinus arrhythmia and heart rate over time across antidepressant-naive subjects, subjects who started using an antidepressant during follow-up, subjects who stopped using an antidepressant, and persistent antidepressant users. Analyses were adjusted for demographics, health, and lifestyle factors.

Results: Compared with continuous nonusers, subjects who started the use of a tricyclic antidepressant or a serotonergic and noradrenergic antidepressant showed a significantly greater increase in heart rate and a decrease of respiratory sinus arrhythmia at 2 years. Subjects who started the use of selective serotonin reuptake inhibitors also showed a decrease in respiratory sinus arrhythmia, but their heart rate did not increase. Discontinuing antidepressants systematically caused opposite effects; levels returned in the direction of those observed among nonusers.

Conclusions: These 2-year longitudinal results indicate that all antidepressants cause a decrease in cardiac vagal control. After discontinuing antidepressants, autonomic function recovers, suggesting that the unfavorable effects are (partly) reversible.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Anxiety Disorders / drug therapy
  • Arrhythmia, Sinus / chemically induced*
  • Depressive Disorder / drug therapy
  • Female
  • Heart Rate / drug effects*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Netherlands
  • Vagus Nerve / drug effects


  • Antidepressive Agents