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Influence of ageing and concurrent psychotropic drugs on dementhylation of tertiary tricyclic antidepressants
Author(s) -
Lein Esa,
Ylitalo Pauli
Publication year - 1991
Publication title -
international journal of geriatric psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 129
eISSN - 1099-1166
pISSN - 0885-6230
DOI - 10.1002/gps.930060908
Subject(s) - doxepin , tertiary amine , tricyclic , amitriptyline , demethylation , pharmacology , chemistry , medicine , organic chemistry , biochemistry , gene expression , dna methylation , gene
The effects of ageing and concurrent psychotropic durgs 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±59 mg, mean ± SD) or amitriptyline (154±47 mg). 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 eldrly and with concurrent neuroleptic therapy.