Study objectives: To compare the steady-state pharmacokinetics of citalopram after multiple-dose administration in elderly and young subjects, and to correlate pharmacokinetic measurements with tolerability.
Design: Single-blind, multiple-dose, dose-escalating, randomized, placebo-controlled trial.
Setting: The Orlando Clinical Research Center, Orlando, Florida.
Subjects: Twenty-four healthy elderly and eight healthy young men and women.
Interventions: Subjects randomized to citalopram received 10 mg once/day for the first week, 20 mg once/day for the second week, and 40 mg once/day for the remaining 3 weeks.
Measurements and main results: Blood samples were collected weekly to determine steady-state pharmacokinetics of citalopram and its primary metabolites. During dose escalation, samples were collected just before dose increase. After the final dose, blood samples were collected periodically over 480 hours to characterize the terminal elimination phase. In elderly subjects, maximum concentration, time associated with the maximum concentration, area under the concentration versus time curve from 0-24 hours, half-life, and volume of distribution were all slightly increased; oral clearance was slightly decreased. However, only half-life was statistically different between the groups, 30% longer in the elderly. In addition, the frequency and severity of adverse events were comparable between the two age groups and did not appear to be dose related.
Conclusions: The pharmacokinetics and tolerability of citalopram in elderly subjects are similar to those observed in younger subjects. The slight differences observed in the elderly likely reflect declining liver and kidney function.