The effects of amitriptyline, citalopram and reboxetine on autonomic nervous system A randomised placebo-controlled study on healthy volunteers

: Penttilä J, Syvälahti E, Hinkka S, Kuusela T, Scheinin H

: 2001

: Psychopharmacology

: Psychopharmacology (Berl)

: 154

: 4

: 343

: 9

: 7

: 0033-3158

DOI: https://doi.org/10.1007/s002130000664

In therapeutic use, amitriptyline, reboxetine and citalopram have all been associated with apparent anticholinergic-like side effects (dry mouth, constipation, etc.), despite the very low antimuscarinic activity of reboxetine and citalopram in vitro.\nWe hypothesised that the spectral analysis of heart rate variability (HRV) might detect differences between amitriptyline, citalopram and reboxetine in their anticholinergic activities following a single peroral administration.\nIn this double-blind, cross-over study, amitriptyline (75 mg), citalopram (20 mg), reboxetine (4 mg) and placebo were randomly given at 1-week intervals to eight healthy male volunteers. Drug and catecholamine concentrations in plasma were determined repeatedly. The drug effect was assessed with periodic recordings of electrocardiogram (ECG) and blood pressure, and with measurements of salivary secretion. The ECG recordings were subjected to spectral analysis of HRV, in which the high frequency (HF) power of R-R interval (RRI) variability was supposed to reflect cardiac parasympathetic tone.\nReboxetine increased heart rate and blood pressure and reduced the HF power of RRI and 3,4-dihydroxyphenylglycol (DHPG) plasma concentrations. Amitriptyline diminished salivary secretion and had a prominent sedative action. Measurements after citalopram did not differ significantly from placebo.\nReboxetine, despite its low antimuscarinic activity in vitro, had distinct effects on the HF power of RRI, consistent with anticholinergic activity in vivo. Amitriptyline had a measurable anticholinergic effect in the salivary glands, but, surprisingly, not in the heart. We suggest that the sedative effect of amitriptyline could alter cardiac sympathovagal balance and, therefore, counteract the anticholinergic drug effect.\nRATIONALE\nOBJECTIVES\nMETHODS\nRESULTS\nCONCLUSIONS