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Influence of ageing and concurrent psychotropic drugs on dementhylation of tertiary tricyclic antidepressants

✍ Scribed by Esa Leinonen; Pauli Ylitalo

Publisher
John Wiley and Sons
Year
1991
Tongue
English
Weight
665 KB
Volume
6
Category
Article
ISSN
0885-6230

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✦ Synopsis

The effects of ageing and concurrent psychotropic drugs on demethylation degree of tertiary tricyclic antidepressants (TCAs) were studied in 340 psychiatric inpatients with depression. They were treated daily with routine therapeutic doses of doxepin (177 f 59 mg, mean f SD) or amitriptyline (154 f 47mg). The numbers of blood samples analysed gas chromatographically for serum concentrations of tertiary TCAs and their secondary amine metabolites were 340 for doxepin and 192 for amitriptyline. The patients were divided into three age groups: <35, 35-65 and > 65 years old. Serum concentrations of doxepin and amitriptyline were increased significantly or showed a trend towards an increase with advancing age, but the concentrations of secondary amine TCAs did not increase at all in the elderly. The ratio of secondary/secondary + tertiary amine TCAs was generally decreased with ageing.

Concurrent neuroleptics, but not benzodiazepines, frequently increased the percentage fraction of secondary amine TCAs. We conclude that the altered demethylation ratio of tertiary amine TCAs, conceivably favouring the altered profile of drug action, should be considered when serum TCA concentrations are monitored in the elderly and with concurrent neuroleptic therapy. KEY woms-Tricyclic antidepressive agents, doxepin, amitriptyline, nortriptyline, psychogeriatrics, pharmacokinetics, drug monitoring.

Treatment results and frequency of side-effects seem to be changed in elderly patients when their depressions are treated with tricyclic antidepressants (TCAs) (Ziegler and Biggs, 1977;Preskorn and Simpson, 1982;Young et al., 1984). This has been linked to age-related increase and variation in serum concentrations of TCAs (

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