Treatment of Alcohol Withdrawal

I wrote two articles with colleagues for our University of Iowa Hospitals and Clinics Pharmacy and Therapeutics News (P & T News) newsletter and both times they were triggered by well-intentioned but misguided physicians attempting to manage alcohol withdrawal with beverage alcohol. This practice is not unheard of but unsupported by medical evidence. The link to the first article is http://www.healthcare.uiowa.edu/pharmacy/PTNews/2001/0102PTNews.html. It was written in 2001 and in 2009 the second attempt to educate colleagues was printed in the April/May P & T News. My co-authors were my clinical pharmacists colleagues, Jill Fowler, PharmD and Joseph Mac, PharmD. The text follows:

Alcohol abuse or dependence occurs in approximately 20% of hospitalized patients in some settings, and in about 40% of emergency room patients [1, 2]. Alcohol withdrawal symptoms are usually minor, though in some patients they may be severe and potentially fatal [1]. Serious complications of alcohol withdrawal include seizures and alcohol withdrawal delirium, commonly called delirium tremens. Seizures usually occur within 6 to 48 hours of cessation of drinking, and patients with a history of alcohol withdrawal seizures are at increased risk[3].

Alcohol withdrawal delirium develops in approximately 5% of untreated patients and is characterized by a disturbance in consciousness with a change in cognition or perceptual disturbances. It typically
does not develop until 2 to 3 days after cessation of drinking [1]. To meet diagnostic criteria for alcohol withdrawal, a patient must have two or more of the following after cessation of (or reduction in) heavy, prolonged alcohol use: autonomic hyperactivity, increased hand tremor, insomnia, nausea and vomiting, transient hallucinations or illusions, psychomotor agitation, anxiety, and grand mal seizures[4]. Pharmacologic treatment is often required to manage troublesome and potentially dangerous symptoms of alcohol withdrawal.

Benzodiazepines

Benzodiazepines are considered to be the treatment of choice for alcohol withdrawal symptoms and for prevention of complications (seizures and alcohol withdrawal delirium). By facilitating the action of the inhibitory neurotransmitter GABA, benzodiazepines suppress the CNS excitation that occurs following cessation of chronic alcohol use. Several randomized, double-blind, placebo controlled trials, as well as years of clinical experience, have established the efficacy of benzodiazepines in reducing signs and symptoms of alcohol withdrawal. In addition, meta-analysis of prospective studies showed that benzodiazepines significantly reduce the incidence of both seizures and alcohol withdrawal delirium [5].

All the benzodiazepines appear to be equally efficacious in treating the symptoms of alcohol withdrawal; therefore, there is no consensus as to the best agent to prescribe. The long-acting agents,
such as chlordiazepoxide and diazepam, generally allow for a smoother course of withdrawal and may provide superior efficacy in prevention of seizures and delirium. The use of intermediate-acting agents, such as lorazepam and oxazepam, may provide additional safety in those patients with severe liver disease or the elderly [2, 5].

Several prospective studies have shown that symptom-triggered administration of benzodiazepines can reduce the overall amount of benzodiazepines needed to treat alcohol withdrawal, helping to
minimize medication side effects and possibly reducing the length of hospital stay[6-8]. Most published studies evaluating symptom-triggered benzodiazepine dosing have based doses on Clinical Institute Withdrawal Assessment Scale for Alcohol (CIWA-Ar) scores. Nurses at UIHC currently assess alcohol withdrawal symptoms using a different scale, which evaluates temperature, pulse, diastolic blood pressure, sweating, tremor, nausea/vomiting, agitation, orientation, and insomnia.

Success of symptom-triggered dosing strategies is dependent on adequate education and training of staff. In cases where this training has not been provided, use of fixed doses of benzodiazepines may be a safer alternative [5]. Examples of fixed-schedule benzodiazepine regimens utilized at UIHC:

Chlordiazepoxide 50 mg PO q 4 hours
for 6 doses then,

Chlordiazepoxide 50 mg PO q 6 hours
for 4 doses then,

Chlordiazepoxide 25 mg PO q 4 hours
for 6 doses

– or –

Lorazepam 2 mg PO q 4 hours for 6
doses then,

Lorazepam 2 mg PO q 6 hours for 4
doses then,

Lorazepam 1mg PO q 4 hours for 6 doses
then,

Lorazepam 1mg PO q 6 hours for 4 doses

The above medication regimens would be initiated when the patient presents with symptoms of withdrawal and meets the threshold of severity based on the structured assessment scale noted previously. The degree of withdrawal severity varies in individual patients, and the dosage of medications may need to be adjusted to adequately control withdrawal symptoms. The scheduled benzodiazepine dose should be held for ataxia, slurred speech, over-sedation, sleeping, or nystagmus. In patients with histories of seizures associated with alcohol withdrawal, it is reasonable to initiate the benzodiazepine regimen prior to emergence of symptoms in order to prevent recurrence of seizures [5].

Potential Adjunctive Agents

Alternative agents are not recommended as monotherapy due to the lack of evidence to support their use as the primary agent for the management of alcohol withdrawal syndrome. Beta-blockers and clonidine have been used to help reduce the severity of withdrawal symptoms, but they do not protect against seizures and could potentiate delirium [5]. Additionally, these agents can mask the symptoms of alcohol withdrawal, leading to inappropriate delays in benzodiazepine therapy. Carbamazepine has evidence to support its effectiveness in treating symptoms of alcohol withdrawal without delirium; however, there is no evidence to support its use in alcohol withdrawal delirium [1, 2, 5].

Neuroleptic agents, such as haloperidol, are commonly used to manage agitation in patients with alcohol withdrawal delirium. However, caution should be used since these agents may lower the seizure threshold and have been associated with a longer duration of delirium and increased mortality [1, 2]. While antihypertensives, anticonvulsants, and neuroleptic agents may have some utility for managing certain symptoms of alcohol withdrawal, all symptoms and complications of alcohol withdrawal can generally be treated with benzodiazepine monotherapy, thereby avoiding the potential adverse effects and drug interactions that may come from prescribing additional agents.

Ethyl Alcohol

Intake of ethyl alcohol (ethanol) reduces the symptoms of alcohol withdrawal, and some practitioners have used intravenous or oral administration of ethyl alcohol for this purpose. The evidence to support this practice is limited and based primarily on uncontrolled studies and case series. A recent randomized, open-label study comparing intravenous ethanol to oral diazepam for management of alcohol withdrawal in trauma patients found no advantage of ethanol over diazepam in terms of efficacy for controlling symptoms or prevention of over-sedation[9].

Intravenous alcohol administration requires monitoring of blood alcohol levels to prevent toxicity, and there is a risk of tissue damage at the injection site [5]. Use of oral ethyl alcohol (in the form of alcoholic beverages) may overcome these complications, though this practice may be viewed as condoning the continued use of alcohol in patients who suffer from alcohol dependence[10].

The dose of oral ethyl alcohol may be difficult to titrate appropriately as it has a short half-life and patients often under-report their regular consumption of alcohol. Additionally, ethyl alcohol is associated with numerous adverse effects, including well-known gastrointestinal, hepatic, hematological, and neurologic toxicities [1, 5]. For these reasons, experts do not recommend the use of ethyl alcohol for treatment of alcohol withdrawal [1, 2, 5].

Vitamin Deficiencies

Patients with alcohol dependence may be malnourished and are often thiamine deficient, putting them at high risk for Wernicke’s encephalopathy and subsequent Wernicke-Korsakoff syndrome. The
administration of thiamine before any source of glucose is recommended to prevent precipitation of Wernicke’s encephalopathy [1, 2]. The current practice at UIHC is to give a one-time 100 mg IM/IV dose of thiamine, followed by 100 mg orally for at least 5 days. Daily folic acid 1 mg orally and a daily multivitamin are also recommended.

Summary

Benzodiazepines are considered the drugs of choice for the management of alcohol withdrawal. Some medications, including haloperidol, may have an adjunctive role in managing alcohol withdrawal symptoms. However, due to toxicity concerns, use of intravenous or oral ethyl alcohol (ethanol) is not recommended in this setting. Both symptom-triggered and fixed-dose benzodiazepine regimens have been shown to be effective for suppressing the symptoms and avoiding the complications of alcohol withdrawal. Vitamin supplementation is also indicated in malnourished alcoholic patients to avoid complications from deficiencies, particularly Wernicke’s encephalopathy.

References

1.            Mayo-Smith, M.F., et al., Management of alcohol withdrawal delirium. An evidence-based practice guideline. Archives of internal medicine, 2004. 164(13): p. 1405-12.

2.            McKeon, A., M.A. Frye, and N. Delanty, The alcohol withdrawal syndrome. Journal of neurology, neurosurgery, and psychiatry, 2008. 79(8): p. 854-62.

3.            Hillbom, M., I. Pieninkeroinen, and M. Leone, Seizures in alcohol-dependent patients: epidemiology, pathophysiology and management. CNS Drugs, 2003. 17(14): p. 1013-30.

4.            American Psychiatric Association. and American Psychiatric Association. Task Force on DSM-IV., Diagnostic and statistical manual of mental disorders : DSM-IV. 4th ed1994, Washington, DC: American Psychiatric Association. xxvii, 886 p.

5.            Mayo-Smith, M.F., Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA : the journal of the American Medical Association, 1997. 278(2): p. 144-51.

6.            Daeppen, J.B., et al., Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Archives of internal medicine, 2002. 162(10):
p. 1117-21.

7.            Saitz, R., et al., Individualized Treatment for Alcohol Withdrawal. JAMA: The Journal of the American Medical Association, 1994. 272(7): p. 519-523.

8.            Weaver, M.F., et al., Alcohol Withdrawal Pharmacotherapy for Inpatients with Medical Comorbidity. Journal of Addictive Diseases, 2006. 25(2): p. 17 – 24.

9.            Weinberg, J.A., et al., Comparison of intravenous ethanol versus diazepam for alcohol withdrawal prophylaxis in the trauma ICU: results of a randomized trial. The Journal of trauma, 2008. 64(1): p. 99-104.

10.          Rosenbaum, M. and T. McCarty, Alcohol prescription by surgeons in the prevention and treatment of delirium tremens: historic and current practice. General Hospital Psychiatry, 2002. 24(4): p. 257-9.

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Comments

  1. K Moylan says:

    I haven’t ‘prescribed’ ethanol to treat alcohol withdrawal, but have seen it done at our hospital. Perhaps this is done because some patients come in for a related problem (ie trauma) but explicitly do not want to go through withdrawal or any kind of alcohol abuse treatment. Why put them through alcohol withdrawal, which can be life threatening, if they have no intention of continued abstinence after discharge? I also struggle with how to handle patients admitted for alcohol withdrawal repeatedly, we have some patients coming in monthly or more often. The hospital seems like its being abused by these patients and I long for some better overall approach to treatment instead of treating each individual episode of abuse (don’t get me wrong, we utilize social workers and refer patients to community based programs, but follow-up is poor and relapses common).

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    • Hi K Moylan,
      I hear you. I wish there were better systems solutions to this challenge. Maybe the motivational interviewing strategy makes the most sense on an individual level. I agree that, at a policy level, it is not obvious what the best approach is to help people who struggle with alcohol dependence move forward. There are probably many specialists out there who have a perspective about it. Maybe we’ll hear from them. Thanks for your comments.

      Best,

      Jim Amos, MD

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