A double-blind comparison of the pharmacodynamic effects of single doses of lofepramine, amitriptyline and placebo in elderly subjects.
In a double-blind five-way cross-over study, six drug free healthy elderly subjects received single oral doses of lofepramine (70 mg, 105 mg and 140 mg), amitriptyline (50 mg) and matched placebo tablets. A dose related increase in plasma drug levels and pharmacological effects of lofepramine was observed. Lofepramine (140 mg) improved psychomotor performance (choice reaction time and letter cancellation), but no such change was seen with lower dose regimes or placebo. No significant differences between lofepramine and placebo were observed in other parameters measured. Amitriptyline, as expected, reduced salivary volume, produced drowsiness and impaired psychomotor performance. These changes correlated with plasma amitriptyline levels. The incidence of subjective side-effects with amitriptyline was also higher than that of lofepramine or placebo. In the dosage used, lofepramine exhibited no deleterious effect on the peripheral cholinergic system or psychomotor performance. This drug therefore is likely to be a relatively safe antidepressant for the elderly, but further investigations during long-term medication are required to verify these observations.
University Department of Geriatric Medicine, Cardiff Royal Infirmary, UK.
K
K
Ghose
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E
Sedman
D000368:Aged; D000639:Amitriptyline / Q000009:adverse effects* / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D003984:Dibenzazepines / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008127:Lofepramine / Q000009:adverse effects* / Q000097:blood; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011674:Pulse / Q000187:drug effects; D011897:Random Allocation; D012472:Salivation / Q000187:drug effects
D003984:Dibenzazepines; D000639:Amitriptyline; D008127:Lofepramine