Treatment of Alcohol Withdrawal Syndrome

Edward DeSimone, RPh, PhD, FAPhA; Jennifer Tilleman, RPh, PharmD, FASCP; Trenton Powell, RPh, PharmD

Disclosures

US Pharmacist 

In This Article

Treatment

The goals for treating AWS are to manage the signs and symptoms of alcohol withdrawal, prevent the progression to serious medical complications, and bridge patients to treatment for maintaining long-term recovery.[10] Patients with very mild symptoms may only need supportive care, while patients with moderate-to-severe symptoms may warrant pharmacologic intervention.[19]

Nutritional Support

Due to the likelihood of nutritional deficiencies in patients with AWS, nutritional support, as tolerated, should be provided. As part of that support, thiamine and folic acid should be routinely administered. Folic acid supplementation of 1 mg daily is recommended. Thiamine supplementation prevents the development of Wernicke's encephalopathy, and a dosage of 100 mg daily should be administered to all patients.[10] In cases where Wernicke's encephalopathy is suspected, high potency vitamins with 500 mg of thiamine are recommended to be given IV three times daily for 3 days.[20]

Magnesium supplementation has also been recommended since serum magnesium levels have been shown to be low during alcohol withdrawal. However, magnesium levels appear to return to normal spontaneously as the AWS approaches conclusion. In addition, magnesium supplementation has demonstrated no benefit in the treatment of AWS.[19]

Drug Therapy

Benzodiazepines. Benzodiazepines are preferred and are considered first-line treatment in patients with AWS.[15,17] These agents reduce the symptoms of withdrawal including seizures and help to prevent symptom progression.[10,15] Long- and intermediate-acting benzodiazepines are used to treat AWS. The long-acting agents include chlordiazepoxide (14- to 100-h half-life of active metabolites) and diazepam (30–100 h). The intermediate-acting agents are lorazepam (12-h half-life), oxazepam (5–15 h), and alprazolam (6–26 h).[21] There is no strong evidence that any one medication is superior in treating AWS. However, it is believed that long-acting benzodiazepines may provide for a smoother withdrawal effect than the intermediate.[10,17] In patients with reduced hepatic function, including the elderly, intermediate-acting agents may be safer because they do not have active metabolites. In addition, these agents have a reduced potential for sedation and respiratory depression.[13,19] Dosages should be individualized to control patient symptoms and, in the case of resistant alcohol withdrawal, very large doses may be necessary, although respiratory depression may be a complication.[13]

There are two separate regimens widely used for administering benzodiazepines for AWS, a fixed-dose schedule and a symptom-triggered dosing schedule (Table 1).[10,13,22] The fixed-dose schedule utilizes specific doses at regular intervals, although it allows for additional doses to be given as needed to further control symptoms.[22] The symptom-triggered regimen utilizes benzodiazepines to be administered only when the patient has significant symptoms represented by a CIWA-Ar score >9. Studies have shown the symptom-triggered regimen can reduce medication use and shorten the duration of treatment.[23,24]

In a study by Daeppen et al comparing symptom-triggered dosing to fixed-schedule dosing using oxazepam to treat alcohol withdrawal, the mean duration of therapy and total dose of oxazepam was 20 hours versus 62.7 hours and 37.5 mg versus 231.4 mg, respectively, with no difference in patient comfort.[23] This study looked at inpatient treatment only.

Other Drug Treatments. Neuroleptic agents such as the phenothiazines and haloperidol may reduce the severity of some withdrawal effects and may be beneficial in patients with uncontrolled agitation, although there is little in the way of controlled clinical data to support their use. In addition, they are not as effective as benzodiazepines in blocking delirium and seizures.[19]

There are some data to suggest that anticonvulsants such as carbamazepine, oxcarbazepine, and divalproex may be useful in the treatment of alcohol dependence by reducing alcohol craving and in treating AWS through its antikindling effect.[25–27] Ironically, these agents did not prevent DTs or seizures.[10] In one study, gabapentin was shown to be effective in treating AWS compared to lorazepam. In addition, it appeared to reduce the craving for alcohol post withdrawal.[28] As with the other anticonvulsants, more controlled trials are needed.

Barbiturates and propofol have been touted as effective in patients with refractory DTs.[29,30] While barbiturates are very inexpensive, few controlled studies have been conducted. In addition, they increase the risk of respiratory depression when combined with alcohol.[19] Little data are available on the use of propofol. However, a major disadvantage to its use is its high cost.[30] Baclofen, a structural analogue of GABA used as a skeletal muscle relaxant, was evaluated as a treatment for AWS. The authors reported that baclofen was as effective as diazepam in treating AWS and shows promise as a treatment option.[31]

However, more controlled clinical trials are needed to measure the efficacy of nonbenzodiazepines in the treatment of AWS and AUD. Until such time as more data are available to support the use of other agents over the benzodiazepines, they will remain the treatment of choice. Drugs used in the treatment of AWS are summarized in Table 2.

Adjunctive Therapy. Adjunctive therapy may need to be added to benzodiazepine therapy depending on the patient's presentation. Beta-blockers and the alphaadrenergic agonist clonidine may be added to reduce adrenergic symptoms such as by lowering blood pressure and heart rate and reducing tremors. However, they do not prevent seizures or delirium.[32] Treatment options may include any of the other agents discussed previously. The selection of which agent to use is based on the specific signs and symptoms that are being targeted. It is important to note that these additional agents should not be recommended as monotherapy when treating AWS.[10]

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