Treatment of Severe Alcohol Withdrawal

Ann Pharmacother. 2016 May;50(5):389-401. doi: 10.1177/1060028016629161. Epub 2016 Feb 9.


Objective: Approximately 50% of patients with alcohol dependence experience alcohol withdrawal. Severe alcohol withdrawal is characterized by seizures and/or delirium tremens, often refractory to standard doses of benzodiazepines, and requires aggressive treatment. This review aims to summarize the literature pertaining to the pharmacotherapy of severe alcohol withdrawal.

Data sources: PubMed (January 1960 to October 2015) was searched using the search termsalcohol withdrawal, delirium tremens, intensive care, andrefractory Supplemental references were generated through review of identified literature citations.

Study selection and data extraction: Available English language articles assessing pharmacotherapy options for adult patients with severe alcohol withdrawal were included.

Data synthesis: A PubMed search yielded 739 articles for evaluation, of which 27 were included. The number of randomized controlled trials was limited, so many of these are retrospective analyses and case reports. Benzodiazepines remain the treatment of choice, with diazepam having the most favorable pharmacokinetic profile. Protocolized escalation of benzodiazepines as an alternative to a symptom-triggered approach may decrease the need for mechanical ventilation and intensive care unit (ICU) length of stay. Propofol is appropriate for patients refractory to benzodiazepines; however, the roles of phenobarbital, dexmedetomidine, and ketamine remain unclear.

Conclusions: Severe alcohol withdrawal is not clearly defined, and limited data regarding management are available. Protocolized administration of benzodiazepines, in combination with phenobarbital, may reduce the need for mechanical ventilation and lead to shorter ICU stays. Propofol is a viable alternative for patients refractory to benzodiazepines; however, the role of other agents remains unclear. Randomized, prospective studies are needed to clearly define effective treatment strategies.

Keywords: alcohol withdrawal; benzodiazepine; critical care; delirium tremens; dexmedetomidine; intensive care; phenobarbital; propofol; refractory; severe.

Publication types

  • Review

MeSH terms

  • Alcohol Withdrawal Delirium / drug therapy
  • Alcoholism / drug therapy*
  • Alcoholism / physiopathology
  • Benzodiazepines / therapeutic use
  • Critical Care
  • Dexmedetomidine / therapeutic use
  • Drug Therapy, Combination
  • Humans
  • Phenobarbital / therapeutic use
  • Propofol / therapeutic use
  • Randomized Controlled Trials as Topic
  • Respiration, Artificial
  • Retrospective Studies
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / physiopathology


  • Benzodiazepines
  • Dexmedetomidine
  • Propofol
  • Phenobarbital