title: Cardiovascular (ECG and systolic time intervals) and anticholinergic effects of repeated doses of femoxetine--a comparison with amitriptyline and placebo in healthy men.
abstract: 1. The cardiovascular and anticholinergic effects of femoxetine and amitriptyline were compared with those of placebo in a double-blind cross-over trial in 12 healthy men. The daily doses administered were therapeutic: 600 mg femoxetine and 150 mg amitriptyline. Duration of treatment with each drug was 13 days. 2. The statistically significant effects on systolic time intervals and ECG comprised a larger decrease of QS2 index during femoxetine than during amitriptyline, and an increase of PEP/LVET ratio and QRS duration by amitriptyline. These results suggest that femoxetine and, to a lesser extent, amitriptyline increase contractility compared with placebo, and amitriptyline, but not femoxetine, causes delay in intracardiac conduction. 3. The effects of amitriptyline on the systolic time intervals are difficult to interpret because of the changes in heart rate and intracardiac electrical conduction caused by the drug. These problems of interpretation are discussed. 4. No significant changes in blood pressure were observed. The heart rate during both femoxetine and amitriptyline periods was significantly faster than during the placebo period, amitriptyline causing a significantly greater increase. 5. Salivary secretion was decreased more by amitriptyline (26%) than by femoxetine (8%), the latter being not significantly different from placebo. Femoxetine tended to increase pupil diameter and amitriptyline to increase accommodation near point, but no visual disturbances were reported on any treatment. Symptoms such as dry mouth, constipation and sedation were significantly less frequently reported during femoxetine than during amitriptyline treatment.
authors.affiliation: Charterhouse Clinical Research Unit, London.
authors.forename: S J
authors.initials: SJ
authors.lastname: Warrington
authors.forename: P
authors.initials: P
authors.lastname: Turner
authors.forename: B K
authors.initials: BK
authors.lastname: Skrumsager
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000639:Amitriptyline / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004311:Double-Blind Method; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D012701:Serotonin / Q000097:blood; D013599:Systole / Q000187:drug effects*
chemical_list: D010880:Piperidines; D000639:Amitriptyline; D012701:Serotonin; C010655:femoxetine