Reduced cardio-respiratory coupling after treatment with nortriptyline in contrast to S-citalopram

J Affect Disord. 2010 Dec;127(1-3):266-73. doi: 10.1016/j.jad.2010.05.010. Epub 2010 Jun 9.


Objective: Major depressive disorder is associated with increased cardiac mortality. A decrease in vagal modulation related to reduced heart rate variability might contribute to increased mortality among many other factors. We sought to examine the hypothesis that nortriptyline treatment will be associated with a decrease in heart rate variability and coupling between heart rate and respiration compared to treatment with S-citalopram.

Methods: Fifty-two patients suffering from major depression were included. Patients were examined unmedicated in the acute stage and after 5weeks of treatment. Twenty-six were reinvestigated after they received S-citalopram and 26, after nortriptyline. We used non-linear measures of heart rate variability and also a novel measure to examine cardio-respiratory coupling to assess cardiac vagal modulation.

Results: There were significant decreases of non-linear measures of heart rate variability in the nortriptyline group in addition to reduced cardio-respiratory coupling in comparison to the group of patients that received S-citalopram. We observed a significant association between the severity of the disease and vagal withdrawal prior to treatment.

Conclusions: These findings indicate that S-citalopram influences autonomic modulation on different regulatory levels to a lesser extent than nortriptyline. Our results have implications for treatment of patients with depression as some of them may already have a higher risk for cardiovascular mortality. In addition, it underlines the beneficial use of SSRIs in patients with cardiac diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / adverse effects*
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Antidepressive Agents, Tricyclic / adverse effects*
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Citalopram / adverse effects*
  • Citalopram / therapeutic use*
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology
  • Electrocardiography / drug effects
  • Female
  • Heart Rate / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Nonlinear Dynamics
  • Nortriptyline / adverse effects*
  • Nortriptyline / therapeutic use*
  • Recurrence
  • Respiration / drug effects*
  • Vagus Nerve / drug effects*


  • Antidepressive Agents, Second-Generation
  • Antidepressive Agents, Tricyclic
  • Citalopram
  • Nortriptyline