The influence of ageing on serum levels of tertiary tricyclic antidepressants

Abstract

The influence of ageing on serum levels of tertiary tricyclic antidepressants (TCAs) was studied in 385 psychiatric inpatients treated daily with one of three TCAs: 157 patients with amitriptyline (154 ± 47 mg, mean dose ± SD), 183 with doxepin (177 ± 59 mg) and 45 with clomipramine (153 ± 51 mg). The patients were divided into three age groups: 125 of them were aged 65 years. The numbers of blood samples for gas-chromatographic monitoring of steady-state concentrations of serum tertiary and secondary TCAs were 192 for amitriptyline, 240 for doxepin and 138 for clomipramine. The concentrations of serum amitriptyline and nortriptyline rose in an age-related manner. The serum clomipramine and norclomipramine concentrations were higher in the middle-aged than in the young patient groups, whereas serum doxepin and nordoxepin concentrations changed less markedly with advancing age. The variations of serum amitriptyline and nortriptyline concentrations were not greater in old patients than in middle-aged ones. Neither were the variations in doxepin and nordoxepin concentrations enlarged with advancing age (but those in clomipramine and norclomipramine concentrations were wider in middle-aged than in young patients). The number of too high (‘toxic’) TCA concentrations was inconsistently greater in the elderly than in the two younger age groups. The results suggest that the liability of old patients to the adverse effects of TCAs is not—at least with all TCA treatments—due to the enlarged variation in serum drug levels or to the increased frequency of ‘toxic’ serum TCA concentrations.