1043-3155 Pediatr Neurol Briefs pedneurbriefs Pediatr Neurol Briefs Pediatric Neurology Briefs Pediatr Neurol Briefs 2166-6482 1043-3155 2166-3155 Pediatric Neurology Briefs Publishers Chicago, IL, USA PNB-1-34-a 10.15844/pedneurbriefs-1-5-5 Seizure Disorders Neurology Pediatrics Nervous System Diseases Child Development Brain Diseases Neurosurgery Child Infant Causes of Antiepileptic Treatment Failure http://orcid.org/0000-0002-0173-7931 Millichap J. Gordon MD 1 2 * Division of Neurology, Children's Memorial Hospital, Chicago, IL Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL Correspondence: Dr. J. Gordon Millichap, E-mail: jgmillichap@northwestern.edu 10 1987 01 08 2016 1 5 34 34 Copyright: © 1987 The Author(s) 1987 This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Causes of treatment failure with antiepileptic drugs vary over time

The Veterans Administration Epilepsy Cooperative Study Group (Regional Epilepsy Center, VA Med Cntr, 4500 S Lancaster Rd, Dallas, TX) have evaluated monotherapy with carbamazepine, phenobarbital, phenytoin, and primidone in a total of 622 patients with previously untreated partial seizures, with particular attention to seizure frequency, neurotoxicity, and systemic toxicity.

 Neurotoxicity Seizure Frequency Neurotoxicity

The Veterans Administration Epilepsy Cooperative Study Group (Regional Epilepsy Center, VA Med Cntr, 4500 S Lancaster Rd, Dallas, TX) have evaluated monotherapy with carbamazepine, phenobarbital, phenytoin, and primidone in a total of 622 patients with previously untreated partial seizures, with particular attention to seizure frequency, neurotoxicity, and systemic toxicity. These 3 factors contributed equally to failure in the first 6 months but systemic toxicity, primarily skin rash, played a relatively minor role in drug failure after that time interval, with the same pattern seen for all drugs studied. After 6 months, failure is determined by seizure frequency and neurotoxicity and is relatively low. A failure rate of 25.3 patients/month during the first 6 months was approx. 6.5 times that during the following 18 months (3.9 patients/month). The first 24 months were critical for successful control since after that time the failure rate falls rapidly to 0.83 patients/month during a 12 month period follow-up. [1]

COMMENT: Such studies would be difficult to duplicate in children although similar results might be expected. That dermatologic, hypersensitivity reactions should occur primarily during the first few months of a new antiepileptic drug (AED) treatment is not surprising. It is likely that the majority would have developed within the first 2 weeks. The incidence of skin rash in the first 6 months of this study involving only adults was 6% and similar to that encountered in children taking phenytoin but higher than that usually reported for carbamazepine (3 to 5%) phenobarbital (1 to 2%) and primidone (rare). AED hypersensitivity reactions are generally more prominent in young children than in adults (e.g. phenytoin, valproate).

 Homan RW Miller B Causes of treatment failure with antiepileptic drugs vary over time Neurology 1987 Oct 37 10 1620 3 3658167 10.1212/WNL.37.10.1620