Adjunctive Phenobarbital for Alcohol Withdrawal Syndrome: A Focused Literature Review

Ann Pharmacother. 2021 Dec;55(12):1515-1524. doi: 10.1177/1060028021999821. Epub 2021 Mar 7.


Objective: To review the literature describing the use of adjunctive phenobarbital in the treatment of severe alcohol withdrawal syndrome (AWS).

Data sources: PubMed and EMBASE were searched using the following terms: phenobarbital, adjunct, refractory or treatment resistant, severe or complicated, and alcohol withdrawal delirium or alcohol withdrawal seizures.

Study selection and data extraction: The search was limited to randomized controlled trials (RCTs) and cohort studies published in English.

Data synthesis: Seven studies were identified in the emergency department (ED; RCT, n = 1; cohort, n = 2), general medicine ward (cohort, n = 1), and intensive care unit (ICU; cohort, n = 3) settings. For all studies set in the ED and general medicine ward and for 1 ICU study, phenobarbital plus symptom-guided benzodiazepine therapy was compared to symptom-guided benzodiazepine monotherapy. The other 2 ICU studies examined adjunctive phenobarbital before and after implementation of a protocol, meaning patients in both arms could have received phenobarbital. Overall risk of bias across all studies was low to moderate.

Relevance to patient care and clinical practice: The specific role of adjunctive phenobarbital in AWS is not clear because a majority of studies are retrospective cohorts with varying primary outcomes in different patient care settings.

Conclusions: In the ED and general medicine ward, phenobarbital demonstrated benzodiazepine-sparing effects. In the ICU, when a protocol guides phenobarbital use, the need for mechanical ventilation may be reduced. Adjunctive phenobarbital was well tolerated. Because of study limitations, it is challenging to provide specific recommendations for adjunctive phenobarbital use in severe AWS.

Keywords: alcohol; and substance abuse; barbuturates; critical care; drug; emergency medicine; general medicine.

Publication types

  • Review

MeSH terms

  • Alcohol Withdrawal Delirium* / drug therapy
  • Alcoholism* / drug therapy
  • Humans
  • Hypnotics and Sedatives / adverse effects
  • Phenobarbital / therapeutic use
  • Substance Withdrawal Syndrome* / drug therapy


  • Hypnotics and Sedatives
  • Phenobarbital