Clinical evidence indicates that parasympatholytic effects of tricyclic ant
idepressants increase with age. The aim of the present study was to determi
ne the possible physiological reason for this phenomenon. Subjects included
23 patients (14 female) with major depression, melancholic type, and 23 ag
e- and sex-matched healthy control subjects. Cardiac vagal tone was measure
d at rest using both spectral analysis and a time domain beat-to-beat metho
d. Results of the spectral and time domain methods for the estimation of va
gal tone used in this study were highly correlated in control subjects as w
ell as in medicated depressed subjects. Both patients and control subjects
showed an age-related decline in cardiac vagal tone. Tricyclic antidepressa
nts decreased vagal tone significantly by 25-49% depending on age (20-60 ye
ars), although the age difference was not significant. The greater effect o
f tricyclic antidepressants on parasympathetic activity typically seen in o
lder age groups may reflect the fact that predrug levels of vagal tone are
already low in older patients. Measurement of vagal tone prior to drug admi
nistration may therefore be of prognostic value for anticholinergic side ef
fects. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.