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

@article{Yasiry2012HowPR,
  title={How phenobarbital revolutionized epilepsy therapy: The story of phenobarbital therapy in epilepsy in the last 100 years},
  author={Zeid Yasiry and Simon D. Shorvon},
  journal={Epilepsia},
  year={2012},
  volume={53}
}
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… 
Novel approaches to anticonvulsant drug discovery
TLDR
It is likely that models of mimic chronic epilepsy will help bridge the gaps and aid in the discovery of novel antiepileptic drugs – ones that can effectively modify the course of the disease.
Brief history of anti‐seizure drug development
TLDR
With the renewed framework and mission of improving the lives of people with epilepsy, the name of the ASP was changed to the Epilepsy Therapy Screening Program (ETSP), and some of the challenges and opportunities for the next generation of drug therapies for the epilepsy field are outlined.
Dosing strategies for antiepileptic drugs: from a standard dose for all to individualised treatment by implementation of therapeutic drug monitoring.
TLDR
There has been a shift in the view of treatment of epilepsy, from "one dose fits all patients" in the early days to individualisation of treatment, and knowledge of pharmacological variability of AEDs has markedly increased through implementation of therapeutic drug monitoring (TDM).
Developing precision treatments for epilepsy using patient and animal models
TLDR
Phenytoin was the first antiepileptic drug discovered in an animal model of seizures whose clinical efficacy was subsequently confirmed and clearly indicated that a search for other AEDs had to consider animal studies.
Exploring the latest avenues for antiepileptic drug discovery and development
TLDR
There is a need for newer drugs, not only aimed at suppressing seizure activity but for the efficient inhibition of epileptogenesis, and there is a possibility of improving the treatment of drug-resistant cases through the rational use of antiepileptic drug combinations.
Pharmacologic treatment of status epilepticus
TLDR
Based on the favourable tolerability profile of levetiracetam and valproate, the authors prefer these drugs in established SE over phenytoin.
Status epilepticus in dogs and cats, part 2: treatment, monitoring, and prognosis.
TLDR
To discuss current anticonvulsant drug options and advances in treatment of status epilepticus (SE) and to review the prognosis associated with SE, a lack of evidence demonstrating clear benefit to the use of specific therapeutics for benzodiazepine-refractory SE is reviewed.
...
...

References

SHOWING 1-10 OF 167 REFERENCES
Phenobarbital Still Has a Role in Epilepsy Treatment
TLDR
It is believed that in patients with mild generalized tonic-clonic seizures phenobarbital could still be the drug of choice since it is cheap, safe, convenient, and effective.
Phenobarbital for the Treatment of Epilepsy in the 21st Century: A Critical Review
TLDR
It is proposed that a pragmatic, comprehensive outcomes program be carried out, perhaps under the aegis of the Global Campaign Against Epilepsy, to optimize the conditions of the use of PB, so that more people around the world can benefit from this cost‐effective medication and live more fulfilling lives.
How did phenobarbital’s chemical structure affect the development of subsequent antiepileptic drugs (AEDs)?
TLDR
The development of nonsedating phenobarbital derivatives will answer a clinical unmet need and might make this old AED more attractive, and the antiepileptic market is therefore crowded.
Carbamazepine versus phenobarbitone monotherapy for epilepsy.
TLDR
An interaction between treatment and seizure type, confirmed statistically, was identified for time to first seizure, where phenobarbitone was favoured for partial onset seizures and carbamazepine for generalized onset tonic-clonic seizures.
Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial.
TLDR
In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs.
Drug treatment of epilepsy in the century of the ILAE: The first 50 years, 1909–1958
TLDR
This paper provides a review of the drug treatment of epilepsy from 1909, the year of the foundation of the International League Against Epilepsy (ILAE), to 1958, when scientific screening was also introduced into drug discovery.
Phenobarbitone versus phenytoin monotherapy for partial onset seizures and generalized onset tonic-clonic seizures.
TLDR
The results of this review favour phenytoin over phenobarbitone, as phenobarbitsone was significantly more likely to be withdrawn than pheny toin, and the higher withdrawal rate with phenobarbarbitone may be due to side effects.
...
...