Comparison of Alcohol Withdrawal Outcomes in Patients Treated with Benzodiazepines Alone versus Adjunctive Phenobarbital: a Retrospective Cohort Study

Background: For treatment of severe alcohol withdrawal syndrome, high dose benzodiazepines (BZDs) may cause delirium and over-sedation. Phenobarbital (PBT) is a long-acting barbiturate effective for the treatment of alcohol withdrawal. Given the potential benefits of PBT, we sought to investigate the effectiveness of PBT as adjunctive treatment for alcohol withdrawal. Methods: This was a retrospective cohort study on patients with a diagnosis of alcohol withdrawal who had a CIWA-Ar score > 10 treated with either BZDs alone (BZD alone group) or BZDs with adjunctive PBT (PBT-adjunct group). The patients received at least one dose of PBT in addition to BZDs (variable doses) in the PBT-adjunct group, and three doses of 20 mg diazepam equivalents within 6 hours in the BZD alone group. The primary endpoint was the proportion of patients with a CIWA-Ar score < 10 at 24 hours after initial treatment. Duration of withdrawal and cumulative dose of BZDs were also assessed. Results: Seven subjects in the adjunctive phenobarbital and 21 in the benzodiazepine group were included in the final analysis. Two patients (28.6%) in the PBT-adjunct group and 5 patients (23.8%) in the BZD only group achieved the primary endpoint, though the difference between the two groups was not statistically significant (P = 0.588). The median (IQR) duration of withdrawal symptoms was 44 (12-62) hours in the PBT-adjunct group compared to 53 (37-87) hours in the BZD only group, with no significant difference between the groups (P = 0.249). The median (IQR) cumulative BZD dose requirement (diazepam equivalent) in the PBT-adjunct group was significantly lower than BZD alone group (25 (20-226) vs. 326 (160-550) mg, P = 0.02). Conclusion: PBT appears to be a safe and effective alternative to BZDs for the treatment of alcohol withdrawal in non-critically ill patients and may be BZD sparing.