High levels of tricyclic antidepressants in conventional therapy: determinant factors

The incidence of potentially toxic serum levels (greater than or equal to 400 ng/ml) was analyzed in a group of 196 monitored patients on a standard dosage regimen (75-225 mg/day) of several antidepressants: imipramine, amitriptyline, nortriptyline, maprotiline and clomipramine. Mean incidence was 12%. The maximum antidepressants serum levels in these patients ranged from 403 to 1,776 ng/ml. The drug/metabolite ratio was 1.5 +/- 0.7. Only in 23% of the cases did the clinical symptoms allow us to suspect the presence of potentially toxic serum levels. The factors that may contribute to the appearance of high serum levels were analyzed; these are: association of neuroleptic agents to the antidepressant therapy, advanced age and administration of doses above 2.5 mg/kg/day. In 64% of the patients, the clinical criteria suggested the need for a reduction in the dose, with a mean value of 42%.