Possible influence of carbamazepine on plasma imipramine concentrations in children with attention deficit hyperactivity disorder

The effect of carbamazepine on the plasma concentration of imipramine and its metabolite desipramine was examined retrospectively in 36 sex- and age-matched children with attention deficit hyperactivity disorder. One-half of the children received imipramine and the other half received combined carbamazepine and imipramine for 1-6 months. The imipramine dosage was significantly higher in the combined treatment group than in the imipramine-only group. Despite receiving larger doses, the combined treatment group had significantly lower mean levels of imipramine, desipramine, and total tricyclic antidepressant compared with those children receiving imipramine alone. Lowered plasma concentrations of tricyclic antidepressants with carbamazepine coadministration have not been reported previously. Although more rigorous studies are needed to confirm these findings, our data suggest that increased imipramine doses may be necessary for adequate response in children on combined therapy. Moreover, toxicity could result upon withdrawal without imipramine dosage adjustment.