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Antiepileptic drugs (AEDs) were frequently used as polytherapy until evidence from a series of studies in the late 1970s and early 1980s suggested that patients derive as much benefit from monotherapy as polytherapy.1–3 AED polytherapy is increasingly becoming popular again and as much as 30–40% of prescriptions to children are polytherapy.4 ,5 The availability of new-generation AEDs in the last two decades has encouraged polytherapy. AEDs such as lamotrigine, topiramate, levetiracetam, oxcarbazepine and zonisamide have been approved for paediatric use and are recommended mostly as adjuncts or as second-line agents.6 Despite the availability of more AEDs, the prevalence of poorly controlled epilepsies still remains the same. About 30% of epilepsies are resistant to treatment.7 Drug-resistant epilepsies almost always require polytherapy, but the question of the best treatment approach when an initial monotherapy fails is still debatable.
Rational polytherapy has been suggested for the treatment of epilepsies. It refers to the use of two or more drug combinations with different mechanisms of action. The goal is to achieve synergistic or supra-additive efficacy. A combination regimen is supra-additive when it produces a total effect that is higher than the effects of the sum of individual drugs. Rational polytherapy sometimes aims to attain infra-additive toxicity such that the component drugs in the polytherapy regimen produce a total toxicity less than the sum of the individual toxicities.8
Clinical evidence in support of rational polytherapy for epilepsy is sparse. A 1997 multicentre European study, involving 347 adults, reported synergism between sodium valproate and lamotrigine.9 Patients given sodium valproate with lamotrigine add-on had better response rate than those given carbamazepine or phenobarbital with add-on lamotrigine. Another multicentre cohort study in Spain showed that lacosamide, a sodium channel blocker, was more effective (with a higher seizure freedom rate and clinical …
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