Preliminary observations of the significance of monitoring tricyclic antidepressant plasma levels in the pediatric patient.
Plasma concentrations of clomipramine and desmethylclomipramine were monitored together with clinical effects over a period of 1--9 months in children and young adolescents (5--19 years of age) receiving clomipramine because of depressive features or enuresis. Data indicate that in the child, clomipramine is rapidly absorbed while its disposition rate is age dependent, as indicated by the significantly lower level:dose ratio (p less than 0.01) observed in the younger groups (5--10; 10--15 years). The incidence of side effects was clearly related to clomipramine plasma concentrations, whereas no relationship could be observed for the desmethyl metabolite. In the case of enuresis, a therapeutic effect was observed at clomipramine concentrations of 20--60 ng/ml, while lower or higher levels were associated with lack of therapeutic effect or adverse effects. No relationship was found between oral daily doses and clomipramine or desmethylclomipramine plasma concentrations. The data point to the usefulness of monitoring drug plasma levels in children undergoing treatment with tricyclic antidepressive drugs.