What is the preferred medication, Phenobarbital (Phenobarb) or Lorazepam (Ativan), for managing symptoms of alcohol withdrawal as measured by the Clinical Institute Withdrawal Assessment (CIWA)?

From the Guidelines

For managing symptoms of alcohol withdrawal as measured by the Clinical Institute Withdrawal Assessment (CIWA), benzodiazepines like Lorazepam (Ativan) are generally preferred over Phenobarbital (Phenobarb) due to their better safety profile and more predictable dose-response relationship.

Key Considerations

• Ativan is typically administered at 1-2 mg IV or PO every 1-2 hours as needed based on CIWA scores, with higher doses for more severe symptoms 1.
• The preference for Ativan stems from its intermediate duration of action, predictable metabolism, and ability to be given through multiple routes, making it particularly useful in patients with liver impairment since it's metabolized differently than other benzodiazepines 1.
• Phenobarbital is typically reserved as a second-line agent for refractory cases or when benzodiazepines are contraindicated, usually starting at 60-130 mg IV or PO, but it carries higher risks of respiratory depression and sedation 1.

Treatment Approach

• The Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) is useful in clinical practice for evaluating the severity of alcohol withdrawal syndrome (AWS) and guiding treatment 1.
• A CIWA-Ar score >8 indicates a moderate AWS and a score ≥15 indicates severe AWS, with pharmacological treatment recommended for both moderate and severe AWS using a symptom-triggered regimen rather than fixed dose schedule 1.
• Benzodiazepines are considered the ‘gold standard’ treatment for AWS, given their efficacy for reducing both withdrawal symptoms and the risk of seizures and/or delirium tremens 1.

Monitoring and Adjustment

• Regardless of medication choice, vital signs and CIWA scores should be monitored regularly, and treatment should be adjusted based on the patient's response 1.
• Thiamine should be given to all patients with AWS (100-300 mg/day) and maintained for 2-3 months following resolution of their withdrawal symptoms to prevent Wernicke encephalopathy 1.

From the Research

Comparison of Phenobarbital and Lorazepam for Alcohol Withdrawal

• The study 2 found that patients who received a single parenteral dose of phenobarbital in addition to symptom-triggered lorazepam had a shorter hospital length of stay and were more likely to be discharged within three days compared to those who received lorazepam only.
• Another study 3 compared phenobarbital-based and lorazepam-based treatment protocols for management of alcohol withdrawal syndrome and found that patients who received phenobarbital had a statistically significant shorter hospital length of stay and lower rates of all-cause 30-day readmission and 30-day ED visits after discharge.
• However, the study 4 compared the efficacy of baclofen and lorazepam in reducing symptoms of alcohol withdrawal syndrome and found that both drugs were comparable in efficacy and tolerability, but did not include phenobarbital in the comparison.
• The study 5 compared lorazepam and chlordiazepoxide in patients with uncomplicated alcohol withdrawal and found that both drugs showed similar efficacy in reducing symptoms of alcohol withdrawal, but did not include phenobarbital in the comparison.
• The study 6 compared symptom-triggered and fixed-schedule dosing of lorazepam in patients hospitalized on general medical wards and found that symptom-triggered dosing resulted in less lorazepam given with similar reduction in CIWA-Ar scores, but did not include phenobarbital in the comparison.

Clinical Institute Withdrawal Assessment (CIWA) Scores

• The study 2 found that median maximum daily CIWA-Ar scores were not statistically significant different between the phenobarbital and lorazepam groups.
• The study 4 found that there were no significant differences in CIWA-Ar scores between the baclofen and lorazepam groups.
• The study 5 found that lorazepam and chlordiazepoxide showed similar efficacy in reducing symptoms of alcohol withdrawal as assessed using the revised Clinical Institute Withdrawal Assessment for Alcohol scale.
• The study 6 found that symptom-triggered dosing of lorazepam resulted in similar reduction in CIWA-Ar scores compared to fixed-schedule dosing.
• The study 3 did not report on CIWA-Ar scores, but found that phenobarbital was associated with a shorter hospital length of stay and lower rates of readmission and ED visits.