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.