This Article  • References  • Full text PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Social Bookmarking   What's this?

A Meta-analysis and Evidence-Based Practice Guideline

Michael F. Mayo-Smith, MD, MPH

JAMA. 1997;278(2):144-151.

Abstract
Objective.
—To provide an evidence-based practice guideline on the pharmacological management of alcohol withdrawal.

Data Soureces.
—English-language articles published before July 1, 1995, identified through MEDLINE search on "substance withdrawal—ethyl alcohol" and review of references from identified articles.

Study Selection.
—Articles with original data on human subjects.

Data Abstraction.
—Structured review to determine study design, sample size, interventions used, and outcomes of withdrawal severity, delirium, seizures, completion of withdrawal, entry into rehabilitation, adverse effects, and costs. Data from prospective controlled trials with methodologically sound end points corresponding to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were abstracted by 2 independent reviewers and underwent meta-analysis.

Data Synthesis.
—Benzodiazepines reduce withdrawal severity, reduce incidence of delirium (-4.9 cases per 100 patients; 95% confidence interval, -9.0 to -0.7; P=.04), and reduce seizures (-7.7 seizures per 100 patients; 95% confidence interval, -12.0 to -3.5; P=.003). Individualizing therapy with withdrawal scales results in administration of significantly less medication and shorter treatment (P<.001). β-Blockers, clonidine, and carbamazepine ameliorate withdrawal severity, but evidence is inadequate to determine their effect on delirium and seizures. Phenothiazines ameliorate withdrawal but are less effective than benzodiazepines in reducing delirium (P=.002) or seizures (P<.001).

Conclusions.
—Benzodiazepines are suitable agents for alcohol withdrawal, with choice among different agents guided by duration of action, rapidity of onset, and cost. Dosage should be individualized, based on withdrawal severity measured by withdrawal scales, comorbid illness, and history of withdrawal seizures. β-Blockers, clonidine, carbamazepine, and neuroleptics may be used as adjunctive therapy but are not recommended as monotherapy.

Author Affiliations
for the American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal

From the American Society of Addiction Medicine Committee on Practice Guidelines.

Footnotes
A complete list of the members of the Working Group on Pharmacological Management of Alcohol Withdrawal appears at the end of this article.

Reprints: California Society of Addiction Medicine, 3803 Broadway, Oakland. CA 94611-5615.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Understanding and Treating Alcohol Craving and Dependence: Recent Pharmacological and Neuroendocrinological Findings
Leggio
Alcohol Alcohol 2009;44:341-352.
ABSTRACT | FULL TEXT  

Dexmedetomidine Infusion as Adjunctive Therapy to Benzodiazepines for Acute Alcohol Withdrawal
Darrouj et al.
The Annals of Pharmacotherapy 2008;42:1703-1705.
ABSTRACT | FULL TEXT  

The alcohol withdrawal syndrome
McKeon et al.
J. Neurol. Neurosurg. Psychiatry 2008;79:854-862.
ABSTRACT | FULL TEXT  

Successful Implementation of an Alcohol-Withdrawal Pathway in a General Hospital
Repper-DeLisi et al.
Psychosomatics 2008;49:292-299.
ABSTRACT | FULL TEXT  

Treatment of alcohol withdrawal syndrome with carbamazepine, gabapentin, and nitrous oxide
Prince and Turpin
Am J Health Syst Pharm 2008;65:1039-1047.
ABSTRACT | FULL TEXT  

Poor Care, Not Poor Protocols, for Alcohol Withdrawal-1
Saitz
Mayo Clin Proc. 2008;83:725-726.
FULL TEXT  

Poor Care, Not Poor Protocols, for Alcohol Withdrawal-3
O'Connor and Lang
Mayo Clin Proc. 2008;83:726-727.
FULL TEXT  

Protocol-Driven Treatment of Alcohol Withdrawal in a General Hospital: When Theory Meets Practice
Berge and Morse
Mayo Clin Proc. 2008;83:270-271.
FULL TEXT  

Inappropriate Use of Symptom-Triggered Therapy for Alcohol Withdrawal in the General Hospital
Hecksel et al.
Mayo Clin Proc. 2008;83:274-279.
ABSTRACT | FULL TEXT  

Alcohol Use and Anxiety: Diagnostic and Management Issues
Brady et al.
Am. J. Psychiatry 2007;164:217-221.
FULL TEXT  

Patient Management Exercise for Substance Abuse: Diagnosis and Treatment
Levine and Albucher
Focus 2007;5:172-183.
ABSTRACT | FULL TEXT  

{gamma}-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment.
Krystal et al.
Arch Gen Psychiatry 2006;63:957-968.
ABSTRACT | FULL TEXT  

Valproic Acid Management of Acute Alcohol Withdrawal
Lum et al.
The Annals of Pharmacotherapy 2006;40:441-448.
ABSTRACT | FULL TEXT  

An audit of symptom triggered chlordiazepoxide treatment of alcohol withdrawal on a medical admissions unit
Hardern and Page
Emerg. Med. J. 2005;22:805-806.
ABSTRACT | FULL TEXT  

Propylene Glycol Toxicity: A Severe Iatrogenic Illness in ICU Patients Receiving IV Benzodiazepines: A Case Series and Prospective, Observational Pilot Study
Wilson et al.
Chest 2005;128:1674-1681.
ABSTRACT | FULL TEXT  

PROPOSAL OF A COMPREHENSIVE CLINICAL TYPOLOGY OF ALCOHOL WITHDRAWAL--A CLUSTER ANALYSIS APPROACH
DRIESSEN et al.
Alcohol Alcohol 2005;40:308-313.
ABSTRACT | FULL TEXT  

Alcohol Withdrawal Syndrome Overlooked and Mismanaged?
McKinley
Crit Care Nurse 2005;25:40-48.
FULL TEXT  

Treatment of Delirium Tremens--Reply
Mayo-Smith
Arch Intern Med 2005;165:587-587.
FULL TEXT  

Unhealthy Alcohol Use
Saitz
NEJM 2005;352:596-607.
FULL TEXT  

Evaluation of a symptom-triggered front-loading detoxification technique for alcohol dependence: a pilot study
Day et al.
Psychiatr. Bull. 2004;28:407-410.
ABSTRACT | FULL TEXT  

Alcohol and Opiate Withdrawal in US Jails
Fiscella et al.
Am. J. Public Health 2004;94:1522-1524.
ABSTRACT | FULL TEXT  

Evidence-Based Guidelines for the Pharmacological Management of Substance Misuse, Addiction and Comorbidity: Recommendations from the British Association for Psychopharmacology
Lingford-Hughes et al.
J Psychopharmacol 2004;18:293-335.
 

Alcohol and the nervous system
McIntosh and Chick
J. Neurol. Neurosurg. Psychiatry 2004;75:iii16-iii21.
FULL TEXT  

Management of Alcohol Withdrawal Delirium: An Evidence-Based Practice Guideline
Mayo-Smith et al.
Arch Intern Med 2004;164:1405-1412.
ABSTRACT | FULL TEXT  

False Positives on the Clinical Institute Withdrawal Assessment for Alcohol--Revised: Is This Scale Appropriate for Use in the Medically Ill?
Bostwick and Lapid
Psychosomatics 2004;45:256-261.
FULL TEXT  

Benign Neglect or Neglected Abuse Drug and Alcohol withdrawal in U.S. Jails
Fiscella et al.
J Law Med Ethics 2004;32:129-136.
 

Intrathecal and Oral Clonidine as Prophylaxis for Postoperative Alcohol Withdrawal Syndrome: A Randomized Double-Blinded Study
Dobrydnjov et al.
Anesth. Analg. 2004;98:738-744.
ABSTRACT | FULL TEXT  

ACUPUNCTURE FOR ALCOHOL WITHDRAWAL: A RANDOMIZED CONTROLLED TRIAL
Trumpler et al.
Alcohol Alcohol 2003;38:369-375.
ABSTRACT | FULL TEXT  

Ethanol in Hospital Formularies--Reply
Blondell et al.
JAMA 2003;289:2361-2361.
FULL TEXT  

Management of Drug and Alcohol Withdrawal
Kosten and O'Connor
NEJM 2003;348:1786-1795.
FULL TEXT  

gamma -Hydroxybutyric Acid and Diazepam Antagonize a Rapid Increase in GABAA Receptors alpha 4 Subunit mRNA Abundance Induced by Ethanol Withdrawal in Cerebellar Granule Cells
Follesa et al.
Mol. Pharmacol. 2003;63:896-907.
ABSTRACT | FULL TEXT  

ALCOHOL WITHDRAWAL TREATMENT IN INTOXICATED VS NON-INTOXICATED PATIENTS: A CONTROLLED OPEN-LABEL STUDY WITH TIAPRIDE/CARBAMAZEPINE, CLOMETHIAZOLE AND DIAZEPAM
Lucht et al.
Alcohol Alcohol 2003;38:168-175.
ABSTRACT | FULL TEXT  

Ethanol in Formularies of US Teaching Hospitals
Blondell et al.
JAMA 2003;289:552-552.
FULL TEXT  

WITHDRAWAL FROM ALCOHOL USING MONITORED ALCOHOL CONSUMPTION: A CASE REPORT
Wright and Thompson
Alcohol Alcohol 2002;37:344-346.
ABSTRACT | FULL TEXT  

The role of magnesium in the emergency department
Kaye and O'Sullivan
Emerg. Med. J. 2002;19:288-291.
ABSTRACT | FULL TEXT  

Symptom-Triggered vs Fixed-Schedule Doses of Benzodiazepine for Alcohol Withdrawal: A Randomized Treatment Trial
Daeppen et al.
Arch Intern Med 2002;162:1117-1121.
ABSTRACT | FULL TEXT  

DOUBLE-BLIND CONTROLLED TRIAL OF {gamma}-HYDROXYBUTYRATE AND CLOMETHIAZOLE IN THE TREATMENT OF ALCOHOL WITHDRAWAL
Nimmerrichter et al.
Alcohol Alcohol 2002;37:67-73.
ABSTRACT | FULL TEXT  

A DOUBLE-BLIND RANDOMIZED PLACEBO-CONTROLLED TRIAL OF LOFEXIDINE IN ALCOHOL WITHDRAWAL: LOFEXIDINE IS NOT A USEFUL ADJUNCT TO CHLORDIAZEPOXIDE
Keaney et al.
Alcohol Alcohol 2001;36:426-430.
ABSTRACT | FULL TEXT  

Regular review: Delirium: optimising management
Meagher
BMJ 2001;322:144-149.
FULL TEXT  

Outpatient Management of Patients with Alcohol Problems
Fiellin et al.
ANN INTERN MED 2000;133:815-827.
ABSTRACT | FULL TEXT  

Managing the heavy drinker in primary care
DTB 2000;38:60-64.
ABSTRACT | FULL TEXT  

A ROLE FOR VALPROATE IN THE TREATMENT OF SEDATIVE-HYPNOTIC WITHDRAWAL AND FOR RELAPSE PREVENTION
Harris et al.
Alcohol Alcohol 2000;35:319-323.
ABSTRACT | FULL TEXT  

IS DAILY SINGLE DOSAGE OF DIAZEPAM AS EFFECTIVE AS CHLORDIAZEPOXIDE IN DIVIDED DOSES IN ALCOHOL WITHDRAWAL -- A PILOT STUDY
Jauhar and Anderson
Alcohol Alcohol 2000;35:212-214.
FULL TEXT  

ZOLPIDEM INVOLVEMENT ON MEMORY AND HYPNOTIC EFFECT OF ETHANOL IN CHRONICALLY ETHANOL-TREATED RATS
Mikolajczak et al.
Alcohol Alcohol 1999;34:511-519.
ABSTRACT | FULL TEXT  

Current concepts in the management of patients with so-called 'minor' or 'mild' head injury
Swann and Teasdale
Trauma 1999;1:143-155.
ABSTRACT  

Alcohol Withdrawal in the Surgical Patient: Prevention and Treatment
Spies and Rommelspacher
Anesth. Analg. 1999;88:946-946.
FULL TEXT  

Lorazepam for the Prevention of Recurrent Seizures Related to Alcohol
D'Onofrio et al.
NEJM 1999;340:915-919.
ABSTRACT | FULL TEXT  

Patients with Alcohol Problems
Garcia-Monco et al.
NEJM 1998;339:130-131.
FULL TEXT  

Patients with Alcohol Problems
O'Connor and Schottenfeld
NEJM 1998;338:592-602.
FULL TEXT  

Review: benzodiazepines are more effective than neuroleptics in reducing delirium and seizures in alcohol withdrawal
Chick
Evid. Based Ment. Health 1998;1:18-18.
FULL TEXT  

Pharmacologic Treatment of Alcohol Withdrawal
Johnson
JAMA 1997;278:1317-1317.
ABSTRACT  

Pharmacologic Treatment of Alcohol Withdrawal
Marinella
JAMA 1997;278:1317-1317.
ABSTRACT  

Pharmacologic Treatment of Alcohol Withdrawal
Wiseman
JAMA 1997;278:1317-1318.
ABSTRACT  

Managing Alcohol Withdrawal: A Meta-Analysis
JWatch Psychiatry 1997;1997:5-5.
FULL TEXT