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Phenytoin and carbamazepine, alone and in combination

Anticonvulsant and neurotoxic effects

Department of Neurology and Neurosurgery (Neurology), Washington University School of Medicine, St. Louis, MO.

Comedication with phenytoin and carbamazepine is frequently used in patients with refractory seizures, although the benefit of this strategy has not been established. To assess whether the combination is a rational anticonvulsant treatment, we determined the therapeutic index (toxicity:efficacy ratio) for the drugs, alone and together, in mice. The individual agents were virtually identical in anticonvulsant and neurotoxic activity, and combined use had no additional therapeutic advantage. Analysis of drug concentrations in brain showed an additive pharmacodynamic interaction for phenytoin and carbamazepine, indicating that the combination is unlikely to be superior to either drug alone. Thus, we find no experimental justification for the simultaneous use of phenytoin and carbamazepine in the treatment of epilepsy.

Address correspondence and reprint requests to Dr. Morris, Washington University School of Medicine, Department of Neurology and Neurosurgery (Neurology), Box 8111, 660 South Euclid Avenue, St. Louis, MO 63110.

Supported in part by an Institutional Neuropharmacology Training Grant from the Public Health Service (#5-T32-NS07129) and by the Seay Neuropharmacology Research Fellowship.

Presented in part at the thirty-sixth annual meeting of the American Academy of Neurology, Boston, MA, April 1984.

Received February 20, 1986. Accepted for publication in final form June 6, 1986.

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