Should Monotherapy for Epilepsy Be Reconsidered?

The critical goal of antiepileptic drug therapy is complete seizure control without side effects. For about half of patients, this goal is achievable with the first drug tried. Standard practice has been to switch to a second monotherapy drug if the first fails. It is time to re-think this strategy because relatively few patients achieve complete control with the second and subsequent monotherapy trials, some patients achieve complete control without intolerable side effects with combination therapy, and the new generations of drugs are easier to use in combination because they are more free of pharmacokinetic and pharmacodynamic interactions. An unanswered question is which combinations are most effective for seizure control. Not all patients are appropriate for polytherapy; some are reasonable candidates for additional monotherapy trials. However, if a polytherapy regimen is working, the wisest plan is often to continue it. Monotherapy still rules, but ‘polypharmacy’ as a pejorative term should be scrapped.