Drug treatment strategies for epilepsy revisited: starting early or late? One drug or several drugs?

There are two popular strategies for current drug treatment of epilepsy; starting early may be better and polytherapy conveys advantages over monotherapy. This review briefly examines if the historical record is much of a guide to determine the clinical value of these two strategies. Great clinical scientists of the 19th and early 20th century, such as Sir William Gowers, and William Aldren Turner, offered vivid single case studies and showed early results of seizure remission in groups of subjects. The historical record offered, however, no evidence of clear clinical benefits for early treatment and polytherapy. Combination treatment was thought to be useful in only some cases. In agreement, current evidence shows no clear clinical benefit of starting treatment early, except perhaps in severe epilepsy. Polytherapy is clinically useful in a subgroup of subjects, but despite being a standard treatment strategy for over one hundred years, it has been poorly studied. In fact, there is no compelling experimental or clinical evidence for a difference in seizure outcome between monotherapy and polytherapy. This surprising finding should prompt a re-appraisal regarding the need to test both strategies separately for the licensing of new antiepileptic drugs.