Why the study?
How do the pharmacokinetics, efficacy, and safety of clomipramine differ in geriatric patients compared to younger patients?
How do the pharmacokinetics, efficacy, and safety of clomipramine differ in geriatric patients compared to younger patients?
Therapeutic drug monitoring of clomipramine is valuable in elderly patients due to impaired metabolism and high interindividual variation, which can lead to severe side effects like hypotension.
Answers are grounded in this paper and cite their sources.
May support TDM to reduce side effects in elderly on clomipramine; hypothesis-generating, needs prospective confirmation before practice change.
Sixty-nine patients, aged 63-98 years and admitted at the Geneva Geriatric Hospital, were included in the present retrospective study. They received clomipramine orally, 50 or 75 mg/day. Blood concentrations of clomipramine were measured as part of a routine drug monitoring program. Comparison with a reference population of patients aged < or = 65 years indicated that elderly patients with concomitant somatic diseases reach higher dose-normalized concentrations of clomipramine and increased parent drug to demethylated metabolite ratios, as a consequence of impaired demethylation (approximately 50%) and hydroxylation (approximately 25%). Sixty-five percent of patients showed clinical improvement, with a maximum rate of satisfactory response observed in major depression. Severe side effects, such as symptomatic hypotension or confusion, were seen in 20% of patients. Because of 10- and 15-fold interindividual variations in the concentrations of clomipramine and its metabolite, respectively, therapeutic drug monitoring can provide valuable assistance to clinical judgment in individual dose adjustment for patients whose old age, associated somatic diseases, and comedication necessitate additional precautions.
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Bocksberger et al. (1994) studied this question.
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