Phenobarbital for epilepsy: much is still to be learnt

Editor—Kale and Perucca contrast the widespread use of phenobarbital for epilepsy in the developing world with its disfavour in the developed world.¹

In the developing world up to two thirds or more of people with epilepsy receive no treatment at all.² With limited resources and infrastructure health authorities' promotion of a cheap but effective drug, phenobarbital, is understandable and desirable. In developed countries the problem is often overtreatment. In the United Kingdom three other standard anti-epileptic drugs (phenytoin, carbamazepine, valproate) have been joined by eight new anti-epileptic drugs in the past 15 years. Polytherapy is increasing. Many doctors are bewildered by the potential choice of drug or drug combinations.

My colleagues and I conducted one of the few randomised efficacy and toxicity studies comparing phenobarbital with other standard anti-epileptic drugs.³,⁴ In adults and children with newly diagnosed generalised or partial seizures long term efficacy was similar for phenobarbital, phenytoin, carbamazepine, and valproate. Neurotoxicity of phenobarbital was only slightly greater in adults but much greater in children. Phenobarbital remains useful in adults but should be used with caution in children if it is the only available drug. When a single drug fails doctors still do not know whether combining two drugs is better than another single drug, or which combination of two drugs is best.⁵

After more than 80 years much is still to be learnt about phenobarbital, the most widely used anti-epileptic drug in the world. The same is true of the standard and newer drugs, and of any combination. To expect the World Health Organization or the International League Against Epilepsy (ILAE) to undertake the necessary clinical trials and basic research is unrealistic. WHO is a public health organisation which promotes best practice within limited existing knowledge and resources, as in the global campaign against epilepsy.² Indeed, scientific institutions in the developing world should undertake such studies, either alone or in collaboration with similar institutions in the developed world, especially designated WHO collaborating centres.