Abstract
Up to 70% of people developing epilepsy may expect to become seizure free with optimum antiepileptic drug (AED) therapy. The remaining 30% are the most difficult to treat. Most patients are controlled on a single AED, but a small proportion requires a combination of two agents. Add-on therapy with a second drug, rather than substitution, may be a viable and rational approach in some patients, particularly if the first drug is relatively well tolerated. Precise classification of the type of seizures, as well as the epilepsy syndrome, together with careful recording of both seizures and adverse effects, are essential if rational management decisions are to be made. The goal of therapy should be complete seizure freedom with a single drug taken once or twice a day and without adverse effects. If control is difficult to achieve, the maximum tolerated dose of each drug should be explored, but a balance needs to be struck between adverse effects and control of seizures. In patients in whom treatment appears to be ineffective, the diagnosis of epilepsy and adherence to therapy should be reviewed. Drugs used in combination must be carefully selected, as poor adherence, drug interactions, and toxicity are more likely if more than one drug is prescribed. Agents are usually chosen according to seizure type, patient characteristics, and often by clinician preference. Those that are better tolerated have a low potential for pharmacokinetic and pharmacodynamic interactions, and those that can be easily introduced without any complicated titration schedule have an advantage.