Hospital Pharmacy - October 2017 - 607

720310
research-article2017

HPXXXX10.1177/0018578717720310Hospital PharmacyHammond et al

Article

Patient Outcomes Associated With
Phenobarbital Use With or Without
Benzodiazepines for Alcohol Withdrawal
Syndrome: A Systematic Review

Hospital Pharmacy
2017, Vol. 52(9) 607-616
© The Author(s) 2017
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https://doi.org/10.1177/0018578717720310
DOI: 10.1177/0018578717720310
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Drayton A. Hammond1, Jordan M. Rowe2, Adrian Wong3,
Tessa L. Wiley4, Kristen C. Lee5, and Sandra L. Kane-Gill6

Abstract
Purpose: Benzodiazepines are the drug of choice for alcohol withdrawal syndrome (AWS); however, phenobarbital is
an alternative agent used with or without concomitant benzodiazepine therapy. In this systematic review, we evaluate
patient outcomes with phenobarbital for AWS. Methods: Medline, Cochrane Library, and Scopus were searched from
1950 through February 2017 for controlled trials and observational studies using ["phenobarbital" or "barbiturate"] and
["alcohol withdrawal" or "delirium tremens."] Risk of bias was assessed using tools recommended by National Heart, Lung,
and Blood Institute. Results: From 294 nonduplicative articles, 4 controlled trials and 5 observational studies (n = 720) for
AWS of any severity were included. Studies were of good quality (n = 2), fair (n = 4), and poor (n = 3). In 6 studies describing
phenobarbital without concomitant benzodiazepine therapy, phenobarbital decreased AWS symptoms (P < .00001) and
displayed similar rates of treatment failure versus comparator therapies (38% vs 29%). A study with 2 cohorts showed similar
rates of intensive care unit (ICU) admission (phenobarbital: 16% and 9% vs benzodiazepine: 14%) and hospital length of stay
(phenobarbital: 5.85 and 5.30 days vs benzodiazepine: 6.64 days). In 4 studies describing phenobarbital with concomitant
benzodiazepine therapy, phenobarbital groups had similar ICU admission rates (8% vs 25%), decreased mechanical ventilation
(21.9% vs 47.3%), decreased benzodiazepine requirements by 50% to 90%, and similar ICU and hospital lengths of stay and
AWS symptom resolution versus comparator groups. Adverse effects with phenobarbital, including dizziness and drowsiness,
rarely occurred. Conclusion: Phenobarbital, with or without concomitant benzodiazepines, may provide similar or improved
outcomes when compared with alternative therapies, including benzodiazepines alone.
Keywords
alcohol withdrawal syndrome, phenobarbital

Introduction
Ethanol is the most frequently abused intoxicant in the
United States.1 According to the National Institute of Alcohol
Abuse and Alcoholism, nearly 88 000 deaths (approximately
62 000 males and 26 000 females) due to alcohol-related
causes occur annually, making excessive alcohol consumption the fourth leading preventable cause of death in the
United States.1 In 2010, more than 1 million people were
hospitalized for alcohol dependence syndrome, and 3.6% of
emergency department (ED) visits included an alcoholrelated diagnosis.2 Mild symptoms frequently develop in
patients withdrawing from alcohol and include autonomic
and neuroexcitatory effects such as tremor, tachycardia,
hypertension, anxiety, and agitation. Symptoms of severe
alcohol withdrawal (AW) occur in fewer than 10% of patients
who present to the ED with alcohol withdrawal syndrome
(AWS) and include delirium tremens (DT) and seizures.3,4

The symptoms when alcohol is abruptly discontinued
after chronic, exaggerated use occur because of a disturbance
in the established homeostasis between excitatory and inhibitory neurotransmitter responses.5 Ethanol increases the
inhibitory effects of the γ-aminobutyric acid type A (GABAA)
receptor complex and decreases excitatory effects from
1

University of Arkansas for Medical Sciences, Little Rock, USA
University of Tennessee Medical Center, Knoxville, USA
3
Brigham and Women's Hospital, Boston, MA, USA
4
University of Nebraska Medical Center, Omaha, USA
5
Orlando Regional Medical Center, FL, USA
6
University of Pittsburgh School of Pharmacy, PA, USA
2

Corresponding Author:
Drayton A. Hammond, Clinical Pharmacy Specialist, Medical and Cardiac
Intensive Care, Department of Pharmacy, Rush University Medical Center,
1653 West Congress Parkway, Chicago, Illinois, 60612, USA.
Email: Drayton.hammond@gmail.com
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