Combination therapy in epilepsy: what, when, how and what not!

The role of combination therapy as a treatment strategy for epilepsy is undergoing reevaluation. A growing appreciation that all seizures cannot be controlled by monotherapy and the introduction of over 14 new antiepileptic drugs (AEDs) for the adjunctive treatment in refractory epilepsy in the past twenty years has triggered an renewed interest in combination therapy. However, the experimental and clinical evidence in support of "rational polytherapy" is sparse, with only the combination of sodium valproate and lamotrigine demonstrating synergism. Robust evidence to guide clinicians on how and when to combine AEDs is lacking and current practice recommendations are largely empirical.