Pharmacology Review

Abstract

The first part of this series (May 2004 NeoReviews ) examined “first-line” antiepileptic drugs (AEDs) for neonatal seizures, including phenobarbital (Pb), phenytoin (PHT), and the benzodiazepines diazepam (DZP) and lorazepam (LZP). This part of the series examines the question of when therapy should be discontinued following control of neonatal seizures and the therapies employed, including metabolic treatments, when neonatal seizures do not respond to standard AEDs. If seizures do not respond to initial treatment with Pb, traditionally PHT is administered, followed by LZP. With ongoing seizures, should treatment continue with a “standard approach,” such as “second-line” AEDs (at usual doses) or should seizures be suppressed with high-dose agents, termed “high-dose suppressive therapy” (HDST)? (1) A specific cause requiring specific treatment should be excluded, if possible, such as basic metabolic disorders, the inborn errors of metabolism (IEM), (2) and certain dependency and deficiency states. Once seizures are controlled, how long should AEDs be continued or should they be discontinued? In older children, treatment duration generally is 1 to 2 years after seizure control is achieved. It is important to differentiate neonatal seizures from neonatal-onset epilepsy (3) because there are major implications for continuing maintenance AED therapy. Neonatal seizures have a higher incidence of symptomatic causes, in which seizures during the acute insult may be an epiphenomenon and may not necessarily persist after resolution of the acute insult. For example, seizures occurring with hypoxic-ischemic encephalopathy may not recur after AEDs are stopped. However, the acute insult may create a chronic epileptic state with ongoing seizures that requires AED treatment. In contrast, there are neonatal-onset epilepsies in which seizures are not caused by an acute insult and may have a genetic basis. These may occur even in the intrauterine period. (4)(5) Neonatal onset-epilepsies include benign neonatal convulsions, benign neonatal familial convulsions, neonatal …