High-dose monotherapy in treatment of intractable seizures

We evaluated the therapeutic efficacy and toxicity of high-dose monotherapy, using carbamazepine or phenytoin, in patients with previously uncontrolled seizures. Treatment with a single drug was equal to or better than polypharmacy, but only a few patients became free of seizures. Toxicity was mild and associated with higher total plasma levels after polypharmacy. Free fractions ranged from 0.14 to 0.30 for carbamazepine and from 0.60 to 0.13 for phenytoin. Toxicity was associated with free phenytoin levels above 3 micrograms/ml; there was no clear relationship between free carbamazepine level and toxicity.