How phenobarbital revolutionized epilepsy therapy: The story of phenobarbital therapy in epilepsy in the last 100 years

Abstract

Summary Phenobarbital (phenobarbitone) was first used as an antiepileptic drug 100 years ago, in 1912. This article tells the story of the discovery of its antiepileptic action, its early development, and the subsequent course of its clinical use over the 100‐year period. The side effects, pharmacokinetics, and misuse of barbiturates are considered, along with the more recent clinical trials and the drug’s current clinical utilization. The introduction of controlled drug regulations, the comparative cost of phenobarbital, and its inclusion on the World Health Organization (WHO) essential drug list are discussed. It is one of the few drugs on the formulary in 1912 that is still listed today, and remarkably its efficacy in epilepsy has not been significantly bettered. The current recommendation by the WHO is that phenobarbital should be offered as the first option for therapy for convulsive epilepsy in adults and children if availability can be ensured. This is rated as a strong recommendation because of the proven efficacy and low cost of phenobarbital, and despite its perceived side‐effect profile and the practical problems of access. Whether this recommendation puts “a hierarchy on the brain,” as has been suggested, is arguable. Much still needs to be learned about the drug’s effects, and the issues raised by phenobarbital have lessons for all antiepileptic drug therapy.

Nodding Syndrome, Western Uganda, 1994

“…26 However, only limited data on the use of VPA in NS are available 7,27 and these do not indicate the greater efficacy of VPA over the alternative AEDs already mentioned. In view of the possibly severe adverse effects of VPA, [28][29][30] the high cost and its difficult availability in rural Africa, it might be reconsidered to abide by the general WHO recommendation to use PHB as the first-line drug, 31,32 especially in patients with coexisting head nodding and convulsive seizures. Controlled comparative studies of different candidate AEDs should be undertaken to improve therapeutic efficiency.…”

Repurposing Valproate, Enteral Clonidine, and Phenobarbital for Comfort in Adult ICU Patients: A Literature Review with Practical Considerations

“…Since that time, more than 2500 derivatives of barbituric acid have been produced. Phenobarbital was first synthesized by Phillip Heinrich Hörlein in 1911 . First used as a hypnotic in 1912, phenobarbital was introduced as an antiepileptic drug in the United States in the 1920s .…”

Slump, tilfeldigheter og antiepileptika

“…However, the drug is cheap, and its long half-life means it is effective even if taken only once a day. In a global perspective, phenobarbital is still an important antiepileptic drug, particularly in developing countries (8), and it features on the World Health Organisation's List of Essential Medicines (9).…”