Phenobarbital in Status epilepticus – Rediscovery of an effective drug.

• Phenobarbital is one of the most effective drugs used in Status epilepticus (SE) and acute seizures, with a good safety profile even in high doses. Sedation, respiratory depression, and hypotension are the most common adverse effects. • Phenobarbital exerts its effect through the enhancement of GABA-ergic inhibition and reduction of glutamatergic excitation via inhibition of AMPA receptors. • Despite the long experience in SE, there are remarkably few clinical trials. Available data suggest that Phenobarbital is at least as good as lorazepam in first-line treatment in early SE and significantly better than valproic acid in benzodiazepine-resistant SE. Phenobarbital (PB) is one of the oldest Antiseizure Medicines (ASMs), which is in clinical use since 1912. Its value in the treatment of Status epilepticus is currently discussed controversially. Phenobarbital has fallen out of favor in many countries across Europe because of reports of hypotension, arrhythmias, and hypopnea. Phenobarbital has a strong antiseizure effect with remarkably little sedation. It exerts its clinical effects, through the increase of GABE-ergic inhibition and decrease of glutamatergic excitation by inhibition of AMPA receptors. Despite good preclinical evidence, there are remarkably few randomized controlled studies on humans in SE, which suggest, that it is at least as good as lorazepam in first-line treatment in early SE, and significantly better than valproic acid in benzodiazepine-resistant SE. Data from randomized trials and large non-randomized prospective and retrospective studies suggest, that Phenobarbital is well tolerated even if used in very high dose protocols. Thus, despite its decline in its popularity at least in Europe and North America, it should be considered a highly cost-effective treatment for early and established SE, not only in resource-limited settings. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022. [ABSTRACT FROM AUTHOR]