Alcohol Withdrawal in the Inpatient Setting

Kylie Lucas, PharmD, BCPS; Glenn R. Grantner, PharmD, BCPS; Jonathan Street, PharmD


US Pharmacist. 2019;44(11):HS-8-HS12. 

In This Article

Pharmacologic Management

Initiation of pharmacologic management of acute alcohol withdrawal is generally based on clinical judgment. In the literature, initiation of pharmacologic therapy is usually recommended only in cases of moderate or severe withdrawal (as designated by a CIWA-Ar score of 8 or higher).[6,20] However, clinicians may deem it is also warranted in patients with a low risk of AWS.


These agents have the most evidence supporting their efficacy; therefore, they are the most commonly used medication class for treating alcohol withdrawal.[5,6,11] BZDs stimulate GABA type A receptors and have been shown to lessen withdrawal severity, including reduced risks of seizures and DT development.[20]

Evidence suggests that all BZDs are effective for treating AWS.[23] Therefore, agents may be selected according to the patient's specific clinical situation. This decision should be based on various differentiating factors in the drugs' pharmacokinetic profiles, primarily duration of action and metabolism (Table 1). In general, BZDs with active metabolites offer a longer duration of action and may result in fewer rebound CNS effects. These longer-acting agents may be inappropriate for some patients, however, such as those with known hepatic disease or at high risk for respiratory depression.[5,20]

Strategies for BZD therapy include loading-dose, fixed-dose, and symptom-triggered regimens. Loading-dose regimens involve administering a high dose of a long-acting BZD every 2 hours and monitoring the patient's CIWA-Ar score before every dose until withdrawal symptoms resolve or the patient is undersedated. A reduced dose may then be administered less frequently on an as-needed basis to maintain the desired effect. This regimen may be preferable, as the duration of therapy is shorter (often not more than 1–2 days, although it may be extended to 72 hours if there is a risk of DT) and the overall dose of BZDs required is lowered.[15,21] Loading-dose regimens may be especially beneficial in patients experiencing severe withdrawal when the risk of withdrawal symptoms outweighs the risk of oversedation. Patients at higher risk for respiratory depression, such as those who are elderly or have concomitant hepatic or respiratory disorders, may be poor candidates for this approach.[5,11,20]

Fixed-dose strategies are less aggressive and more patient-specific. An initial total daily dose of BZDs may be determined based on a patient's average daily alcohol consumption (see Box 1 for formula).[24] Every 10 grams of alcohol are equivalent to one drink and should be countered with 5 mg of diazepam. This dose should then be adjusted for patient comorbidities, risk of accumulation, and amount of time since the patient's last drink. Long-acting BZDs are recommended owing to the low risk of breakthrough symptoms, although individual patient assessment should dictate the most appropriate agent. The dose is then tapered at scheduled intervals based on continued monitoring, which results in an extended therapy duration compared with loading-dose regimens. This approach is beneficial when barriers to close monitoring exist or CIWA-Ar scores are difficult to determine.[5,11,20]

Symptom-triggered dosing, a more reactive approach, requires the most monitoring and is based specifically on CIWA-Ar score. This regimen is not appropriate for all patients, but it may reduce the risk of overmedicating. It is not recommended for use in any patient who has previously experienced withdrawal seizures or DT. The patient must also be capable of reporting any withdrawal symptoms being experienced. Although symptom-triggered therapy may have limited applicability, it has demonstrated a reduced duration of therapy and lower cumulative dose compared with fixed-dose regimens.[25] Patients without a history of previous withdrawal complicated by seizures or DT who have a moderate withdrawal risk according to CIWA-Ar scores may benefit from this regimen.[5,11,20]


Phenobarbital has been investigated as a treatment option for AWS. The potential mechanism for its benefit is a direct effect on the GABA neurochemical pathway that offers a cross-tolerance effect with alcohol. Research on the use of phenobarbital for AWS has historically produced mixed results.[20,26,27] However, recent literature has yielded more encouraging data. A retrospective cohort study of ICU patients evaluated treatment with a symptom-triggered BZD regimen versus phenobarbital.[26] The phenobarbital cohort demonstrated significantly shorter ICU stays and overall hospitalization than the standard-of-care BZD cohort. The phenobarbital cohort also required fewer intubations and adjunctive agents for further symptom control. It was concluded that phenobarbital may be an effective alternative to traditional BZD therapy.[26]


Some anticonvulsant agents may also be useful for the management of AWS. Anticonvulsants have been shown to reduce cravings and treat mood disorders, both of which may occur in AWS patients. Although anticonvulsants' side-effect profiles vary by agent, they are generally less sedating than BZDs, which may be an advantage in some situations.[20,28]

Carbamazepine (CBZ) is one of the most investigated anticonvulsants for AWS, and research suggests that CBZ may be a suitable alternative to traditional BZD therapy. A study that compared CBZ with lorazepam in an outpatient setting concluded that, in addition to being effective, CBZ was superior for preventing rebound withdrawal symptoms.[29] Although CBZ appears to be useful for treatment of AWS, evidence is inconclusive regarding its efficacy in treating withdrawal-associated seizures and DT compared with BZDs.[30] This deficit, combined with associated side effects and drug interactions, has generally limited the use of CBZ in this setting.

Other anticonvulsants have also been evaluated, including valproic acid, gabapentin, and vigabatrin. Although findings are more limited than for BZDs and CBZ, all of these agents have demonstrated benefit in AWS and could be considered alternative therapies. Each agent's adverse-effect profile should be taken into account, especially those of valproic acid. Although valproic acid may be effective, its use is generally limited by side effects that mimic the CNS and GI disturbances that commonly occur in AWS.[20,28–33]

Adrenergic Drugs

Both adrenergic agonists (e.g., clonidine) and adrenergic antagonists (e.g., propranolol) have been used to treat symptoms of AWS. The benefit is theorized to be linked to reductions in blood pressure and heart rate, which lead to an overall decrease in autonomic response. Evidence generally does not support the use of adrenergic medications for prevention or treatment of withdrawal-associated delirium or seizures. The use of adrenergic medications is limited to adjunctive therapy with BZD treatment, and monotherapy should not be used in patients whose CIWA-Ar category exceeds low risk.[20,34]