Phenobarbital, also known as phenobarbitone or phenobarb, is a medication recommended by the World Health Organization for the treatment of certain types of epilepsy in developing countries. In the developed world, it is commonly used to treat seizures in young children, while other medications are generally used in older children and adults. It may be used intravenously, injected into a muscle, or taken by mouth. The injectable form may be used to treat status epilepticus. Phenobarbital is occasionally used to treat trouble sleeping, anxiety, and drug withdrawal and to help with surgery. It usually begins working within five minutes when used intravenously and half an hour when administered orally. Its effects last for between four hours and two days.
Side effects include a decreased level of consciousness along with a decreased effort to breathe. There is concern about both abuse and withdrawal following long-term use. It may also increase the risk of suicide. It is pregnancy category B or D (depending on how it is taken) in the United States and category D in Australia, meaning that it may cause harm when taken by pregnant women. If used during breastfeeding it may result in drowsiness in the baby. A lower dose is recommended in those with poor liver or kidney function, as well as elderly people. Phenobarbital is a barbiturate that works by increasing the activity of the inhibitory neurotransmitter GABA.
Phenobarbital was discovered in 1912 and is the oldest still commonly used anti-seizure medication. It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system.
Phenobarbital is used in the treatment of all types of seizures, except absence seizures. It is no less effective at seizure control than phenytoin, however phenobarbital is not as well tolerated. Phenobarbital may provide a clinical advantage over carbamazepine for treating partial onset seizures. Carbamazepine may provide a clinical advantage over phenobarbital for generalized onset tonic-clonic seizures. Its very long active half-life (53–118 hours) means for some people doses do not have to be taken every day, particularly once the dose has been stabilized over a period of several weeks or months, and seizures are effectively controlled.
The first-line drugs for treatment of status epilepticus are benzodiazepines, such as lorazepam or diazepam. If these fail, then phenytoin may be used, with phenobarbital being an alternative in the US, but used only third-line in the UK. Failing that, the only treatment is anaesthesia in intensive care. The World Health Organization (WHO) gives phenobarbital a first-line recommendation in the developing world and it is commonly used there.
Phenobarbital is the first-line choice for the treatment of neonatal seizures. Concerns that neonatal seizures in themselves could be harmful make most physicians treat them aggressively. No reliable evidence, though, supports this approach.
Phenobarbital is sometimes used for alcohol detoxification and benzodiazepine detoxification for its sedative and anti-convulsant properties. The benzodiazepines chlordiazepoxide (Librium) and oxazepam (Serax) have largely replaced phenobarbital for detoxification.
Phenobarbital properties can effectively reduce tremors and seizures associated with abrupt withdrawal from benzodiazepines.
Phenobarbital is a cytochrome P450 inducer, and is used to reduce the toxicity of some drugs.
Phenobarbital is occasionally prescribed in low doses to aid in the conjugation of bilirubin in people with Crigler–Najjar syndrome, type II, or in patients with Gilbert’s syndrome.
Phenobarbital can also be used to relieve cyclic vomiting syndrome symptoms.
Phenobarbital is a commonly used agent in high purity and dosage for lethal injection of “death row” criminals.
In infants suspected of neonatal biliary atresia, phenobarbital is used in preparation for a 99mTc-IDA hepatobiliary (HIDA; hepatobiliary 99mTc-iminodiacetic acid) study that differentiates atresia from hepatitis or cholestasis.
Phenobarbital is used as a secondary agent to treat newborns with neonatal abstinence syndrome, a condition of withdrawal symptoms from exposure to opioid drugs in utero.
In massive doses, phenobarbital is prescribed to terminally ill patients to allow them to end their life through physician-assisted suicide.
Sedation and hypnosis are the principal side effects (occasionally, they are also the intended effects) of phenobarbital. Central nervous system effects, such as dizziness, nystagmus and ataxia, are also common. In elderly patients, it may cause excitement and confusion, while in children, it may result in paradoxical hyperactivity.
Phenobarbital is a cytochrome P450 hepatic enzyme inducer. It binds transcription factor receptors that activate cytochrome P450 transcription, thereby increasing its amount and thus its activity. Due to this higher amount of CYP450, drugs that are metabolized by the CYP450 enzyme system will have decreased effectiveness. This is because the increased CYP450 activity increases the clearance of the drug, reducing the amount of time they have to work.