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There is increasing enthusiasm for the active control trial for newly diagnosed patients with epilepsy as well as conditions such as hypertension and heart failure. For many diseases, especially epilepsy, placebo-controlled trials are ethically difficult to justify when drugs are tested as monotherapy. Second, placebo-controlled trials often leave the clinician unsatisfied. For example, when 1200 mg of oxcarbazepine was tested vs placebo in newly diagnosed patients with frequent seizures, the study demonstrated that oxcarbazepine was superior to placebo.1 However, demonstrating that treatment is better than “nothing” does not help clinicians to select optimal therapy. When there are many treatment options, the crucial question that most clinicians would like answered is not one of effective therapy, but of best therapy. Hence, the intrinsic appeal of the head-to-head comparison.
In this issue of Neurology, Gamble et al. report a meta-analysis of five randomized controlled trials of lamotrigine vs carbamazepine using individual patient data.2 Carbamazepine is an older antiepileptic drug, whereas lamotrigine is one of the better tolerated …
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