What is the role of phenobarbital in the treatment of delirium tremens (DTs)?

Updated: Nov 06, 2020
  • Author: Michael James Burns, MD, FACEP, FACP, FIDSA; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, FAPS, MCCM  more...
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Answer

Phenobarbital, a long-acting barbiturate with a half-life of 80-120 hours and a duration of sedation of 4-10 hours, has been used successfully in the treatment of alcohol withdrawal and DTs. It has well-documented anticonvulsant activity, is inexpensive, and can be administered by the oral, intramuscular, or IV route. Although its mechanism of action is mediated by GABA at the GABA-A receptor, its mechanism of action is different from the benzodiazepines as well as the short-acting barbiturates. While benzodiazepines increase the frequency of chloride channel opening caused by GABA-A receptor activation requiring the presence of presynaptic GABA, phenobarbital enhances GABA-A chloride currents by increasing the duration of chloride channel opening. Therefore, phenobarbital and benzodiazepines may have synergistic clinical effects, supporting the use of phenobarbital as an adjunct to benzodiazepines.

However, compared with benzodiazepines, even at high doses, phenobarbital has a greater risk of respiratory depression and hypotension and has a lower overall safety profile. It is generally recommended to be reserved for use as an alternative agent when benzodiazepines cannot be used or have not been effective. [22] Some authorities have recommended phenobarbital as a first-line agent to be given as an initial single large dose up to 10 mg/kg or preferably as repeated small doses (65, 130, or 260 mg IV per dose) for loading until the patient is calm, to be followed by use of benzodiazepines on an as-needed, symptom-triggered basis.


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