The SANAD study also compared valproate, lamotrigine, and topiramate in patients newly diagnosed with generalized or unclassified epilepsy. Lamotrigine and topiramate were not as effective as valproate. A randomized, double-blind study of childhood absence epilepsy by Glauser et al found that valproate and ethosuximide were associated with a higher likelihood of seizure freedom at 20 weeks than lamotrigine. Ethosuximide was associated with fewer cognitive side effects, compared with valproate.
What Is the Right Dose?
When choosing the appropriate dosage for a patient, a neurologist must balance the need for a rapid onset of therapeutic effects against the risks of side effects. Lamotrigine and topiramate, for example, require slow titration to minimize side effects. “If you need to control the seizures rapidly, then a drug that needs a slow titration may not be the best choice,” said Dr. Perucca.
A neurologist may want to start a patient on a low dose and monitor his or her response. If it is crucial to minimize the risk of seizure recurrence, a high initial dose may be given, but this dose increases the risk of side effects. Data do not indicate whether nonresponders should be given the highest tolerated dose, or whether a biomarker such as serum drug level should define the highest practical dose.
Recent research indicates that many people with newly diagnosed epilepsy do not need large doses of medication. Most patients have good outcomes with doses of carbamazepine that are 600 mg or less, doses of valproate that are 1 g or less, or doses of lamotrigine that are 200 mg or less. In a large study of levetiracetam and carbamazepine, 90% of the patients who achieved seizure freedom did so with 400 mg/day of carbamazepine or 1 g/day of levetiracetam. “You gain little by giving larger doses,” said Dr. Perucca. “If you manage to keep the dose low—and you can in the majority of patients—then you don’t need necessarily to encounter side effects.”
—Erik Greb