Autonomic neurocardiac function in patients with major depression and effects of antidepressive treatment with nefazodone

Background: Major depression (MD) is associated with an augmented risk of cardiovascular mortality. One possible explanation for this association is that MD influences autonomic neurocardiac regulation (ANR). However, previous studies on this subject revealed conflicting results. Methods: Using an autonomic test battery, which consisted of standardised measurements of heart rate variability (HRV) and blood pressure, we (1) compared ANR between 25 patients with DSM-III-R diagnosed MD and 60 healthy controls, and (2) investigated the autonomic effects of antidepressive treatment with nefazodone. Results: Following multivariate analysis of all tests a significant reduction in HRV could only be shown for the Valsalva ratio amongst the depressives compared to controls. There was a significant inverse correlation between the HRV during deep respiration and both the severity of depression and the duration of the depressive episode. Serial HRV recordings revealed that both the mean resting heart rate and systolic blood pressure significantly decreased after 21 days of nefazodone treatment (average dosage 413 mg/day), whereas after 10 days (average dosage 270.8 mg/day) there were no striking changes compared to the pre-treatment values. During nefazodone treatment no significant changes in parasympathetic tone occurred. Limitations: ANR was not assessed in a randomised, placebo-controlled fashion. Conclusions: (1) Patients with MD may suffer from functional disturbances in the interaction between the sympathetic and parasympathetic autonomic tree. (2) The pattern of autonomic changes during treatment suggests that nefazodone induced a dose dependent, serotonergically-mediated down-regulation of the sympathetic tone. This mechanism might be responsible for nefazodone’s properties of reducing anxiety.