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

Rationale: In therapeutic use, amitriptyline, reboxetine and citalopram hav e 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. Objectives: We hypothesised that the s pectral analysis of heart rate variability (HRV) might detect differences b etween amitriptyline, citalopram and reboxetine in their anticholinergic ac tivities following a single peroral administration. Methods: In this double -blind, cross-over study, amitriptyline (75 mg), citalopram (20 mg), reboxe tine (4 mg) and placebo were randomly given at I-week intervals to eight he althy male volunteers. Drug and catecholamine concentrations in plasma were determined repeatedly. The drug effect was assessed with periodic recordin gs 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) variab ility was supposed to reflect cardiac parasympathetic tone. Results: Reboxe tine increased heart rate and blood pressure and reduced the HF power of RR I and 3,4-dihydroxyphenylglycol (DHPG) plasma concentrations. Amitriptyline diminished salivary secretion and had a prominent sedative action. Measure ments after citalopram did not differ significantly from placebo. Conclusio ns: Reboxetine, despite its low antimuscarinic activity in vitro, had disti nct effects on the HF power of RRI, consistent with anticholinergic activit y in vivo. Amitriptyline had a measurable anticholinergic effect in the sal ivary glands, but, surprisingly, not in the heart. We suggest that the seda tive effect of amitriptyline could alter cardiac sympathovagal balance and, therefore, counteract the anticholinergic drug effect.