Conversion to monotherapy: clinical trials in patients with refractory partial seizures.

The efficacy, tolerability, and safety of a potential antiepileptic drug (AED) are initially evaluated in clinical trials employing add-on designs. When positive, those trials allow us only to conclude that the study drug is efficacious when administered as adjunctive therapy. However, to demonstrate efficacy and safety as monotherapy, the drug must be evaluated using a monotherapy trial design. Such a design needs to take into account important methodologic issues that can affect clinical relevance and/or raise ethical concerns. This review critically assesses two monotherapy trial designs: outpatient conversion to monotherapy and presurgical conversion to monotherapy in patients with medically refractory seizures of partial onset. The efficacy and safety data derived from published studies of AED monotherapy in patients with partial-onset seizures that utilize these trial designs are evaluated and the advantages and disadvantages of each trial design are discussed.