Abstract

PIP: 3 interaction studies have been performed in endogenously depressed patients to examine the effects of age, cigarette smoking, and (OCs) oral contraceptives on steady-state plasma concentrations of clomipramine and its pharmacologically active desmethyl metabolite. Patients received daily doses of the drug for at least 4 weeks and had their drug and metabolite levels measured at weekly intervals. Clinical response and tolerability were also assessed at these times. Older patients achieved higher steady-state plasma concentrations of clomipramine and desmethylclomipramine than did their younger counterparts. They were also less able to tolerate drug therapy, a result of the increased drug and metabolite levels. Both young and elderly patients showed a significant clinical improvement although there was some indication that response was slower in the older age groups. Patients smoking 15 or more cigarettes a day were found to tolerate daily doses of 75 mg clomipramine far better than nonsmokers, and this was reflected in lower drug levels in the smoking group. Nonsmokers also failed to achieve steady-state conditions during the first 7 days of treatment and the mean levels gradually increased over the study period. Interestingly, there were no differences in desmethyl metabolite levels in the 2 groups. Both smokers and nonsmokers improved significantly during treatment, and there were no significant differences in the response of the completers in the 2 groups. Finally, no interaction between clomipramine and OCs was observed, and there was no evidence to suggest that patients on OCs tolerated treatment or responded better than did patients not receiving these drugs. Plasma clomipramine levels were also virtually identical in the 2 groups.