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INTRODUCTION

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Following the diagnosis of epilepsy and making the decision to start a treatment, as discussed in the prior chapter, the clinician must choose the most appropriate initial medication. This decision requires knowledge of the clinical pharmacology of medications used for the treatment of epilepsy and an ability to individualize treatment to the child in question.1 The ultimate goal is complete control of seizures without producing adverse effects. Although the perfect drug does not exist, the current therapeutic armamentarium offers a broader range of choices than available ever before with each drug having some advantages and disadvantages. A single drug should be chosen so that the child is treated with monotherapy, which has the likelihood of producing the fewest number of side effects.2,3 The first issue in deciding upon initial therapy depends on seizure type. An appreciation of epilepsy syndrome is also extremely important, as it may select for or against an agent and may exacerbate seizure types, which have not been yet appreciated in the child.

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Besides the expected efficacy of the medication for the seizure type(s), other important aspects that must be considered in children with epilepsy include the spectrum of toxicity, side effects, likelihood of compliance, ease of administration, and the potential for additional side effects following long-term therapy, if prolonged treatment is thought to be probable. Besides possible immediate age-specific organ toxicities, potential side effects affecting cognition and behavior must be considered. Effects upon daily activity such as sleeping, eating, and behavior are of most concern to caregivers, but the potential for developing rare but life-threatening adverse effects must be carefully reviewed and appropriately discussed.

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FINDING THE DRUG OF CHOICE

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Following the establishment of the need to treat and having a clear description of seizure type, the clinician and caregiver should together decide upon initial therapy. The clinician advising the family regarding antiepileptic drug (AED) use will frequently recommend an agent that is comfortable.

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This comfort comes from prior experience in prescribing the medication, recommendations of experts and peers derived from multiple types of studies. For some, randomized clinical trials (RCTs) offer the strongest evidence concerning which AEDs should be selected as first line.

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THE ROLE OF CLINICAL TRIALS IN CHOOSING A DRUG

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RCTs of AEDs applicable to treatment of children with epilepsy are performed only following studies in adults with refractory partial seizures. Pediatric partial seizure trials are initiated and then recommendations follow. Specialized studies in children with the Lennox–Gastaut syndrome and childhood absence epilepsy have only recently generated specific recommendations for the use of AEDs in these disorders.1 Thus, the timing of the performance and reporting of the most rigorous type of studies applicable to the treatment of children with epilepsy may be substantially delayed following the approval and introduction of a newer AED. A discussion of clinical trials versus antedoctal reports ...

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