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

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. 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. 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). 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.