[Anticonvulsant combination therapy: rational concepts versus real effectiveness]

Abstract

Primary drug treatment of epilepsies is usually a monotherapy with an antiepileptic drug. This procedure causes less side effects as polytherapy and probably shows the same efficacy. Two third of patients with focal epilepsies are sufficiently treated with a single antiepileptic drug: 60% of patients with Grand mal and 22-30% of patients with complex focal seizures remain seizures free. An alternative monotherapy will suppress seizures in another 30% of patients. With polytherapy this is achieved in only 12% of the remaining patients, furthermore, side effects increase in polytherapy. Generalized epilepsies are usually treated with valproate monotherapy. Patients remain seizure free from absence in 60-90%, from myoclonic-impulsive seizures in 75-97% and from Grand mal in about 85%. Alternative monotherapy is less common because of the limited efficacy and possible side effects of drugs: ethosuximide does not control Grand mal and phenobarbitone may cause sedation. Thus, polytherapy is commonly initiated when monotherapy fails to control seizures (lamotrigine is often chosen as comedication). Rational polypharmacy is a term suggesting rational concepts in planning antiepileptic polytherapy leading to a superior anticonvulsant effect. However, this consideration is not based on or supported by clinical data. Yet, a combination of drugs which have no or little pharmacokinetic interactions seems to be a clinically relevant recommendation. Thus, newly developed drugs such as vigabatrin, lamotrigine or gabapentin are more frequently used as comedication with standard antiepileptic drugs.