Role of α2-agonists in the Treatment of Acute Alcohol Withdrawal

Andrew J Muzyk PharmD; Jill A Fowler PharmD; Daryn K Norwood PharmD; Allison Chilipko PharmD


The Annals of Pharmacotherapy. 2011;45(5):649-657. 

In This Article

Abstract and Introduction


Objective: To evaluate literature reporting on the role of norepinephrine in alcohol withdrawal and to determine the safety and efficacy of α2-agonists in reducing symptoms of this severe condition.
Data Sources: Articles evaluating the efficacy and safety of the α2-agonists clonidine and dexmedetomidine were identified from an English-language MEDLINE search (1966-December 2010). Key words included alcohol withdrawal, delirium tremens, clonidine, dexmedetomidine, α2-agonist, norepinephrine, and sympathetic overdrive.
Study Selection and Data Extraction: Studies that focused on the safety and efficacy of clonidine and dexmedetomidine in both animals and humans were selected.
Data Synthesis: The noradrenergic system, specifically sympathetic overdrive during alcohol withdrawal, may play an important role in withdrawal symptom development. Symptoms of sympathetic overdrive include anxiety, agitation, elevated blood pressure, tachycardia, and tremor. Therefore, α2-agonists, which decrease norepinephine release, may have a role in reducing alcohol withdrawal symptoms. The majority of controlled animal and human studies evaluated clonidine, but the most recent literature is from case reports on dexmedetomidine. The literature reviewed here demonstrate that these 2 α2-agonists safely and effectively reduce symptoms of sympathetic overdrive and concomitant medication use. Dexmedetomidine may offer an advantage over current sedative medications used in the intensive care unit, such as not requiring intubation with its use, and therefore further study is needed to fully elicit its benefit in alcohol withdrawal.
Conclusion: Clonidine and dexmedetomidine may provide additional benefit in managing alcohol withdrawal by offering a different mechanism of action for targeting withdrawal symptoms. Based on literature reviewed here, the primary role for clonidine and dexmedetomidine is as adjunctive treatment to benzodiazepines, the standard of care in alcohol withdrawal.


Alcohol dependence represents approximately 20% of hospital admissions and acute alcohol withdrawal constitutes a serious medical emergency requiring prompt recognition to prevent withdrawal complications.[1] Acute alcohol withdrawal may progress to a medical emergency through the development of seizures and delirium tremens: cloudy consciousness, severe autonomic instability, hallucinations, and agitation.[2] While 86% of patients with withdrawal will experience common signs and symptoms including agitation, tremor, hypertension, and tachycardia, approximately 5% of these patients may develop more severe symptoms consistent with delirium tremens (DTs).[3]

Benzodiazepines remain the standard of treatment for withdrawal seizures and DTs, although α2-agonists may have an adjunctive role in reducing sympathetic overdrive and associated symptom manifestations.[4–6] The majority of literature on α2-agonists evaluates the 2 older agents, lofexidine[7–13] and clonidine.[14–24] However, recent case reports on dexmedetomidine, a newer α2-agonist, have generated interest in this drug class for alcohol withdrawal management.[25–28]

The purpose of this article is to review the evidence for α2-agonists in alcohol withdrawal and to examine their place in therapy.


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