Patients with alcohol withdrawal syndrome (AWS) who were treated with phenobarbital had similar outcomes and lengths of hospital stays compared with those who were treated with the long-acting benzodiazepine diazepam, according to a study published in JAMA Internal Medicine.Why It’s Relevant
While benzodiazepines are the standard treatment for acute AWS, the medications can result in respiratory distress and delirium. Phenobarbital has become an increasingly popular alternative because it has stable pharmacokinetics and uses weight-based dosing. However, evidence for its use has largely relied on comparisons with lorazepam, a short-acting benzodiazepine. Few studies have compared phenobarbital with long-acting benzodiazepines, which are recommended by clinical guidelines.
By the Numbers
- Researchers analyzed data for 23,643 patients with AWS (median age 45 years, 75% male) who received either phenobarbital or diazepam on the day of hospital admission.
- Between the 48% of patients who received phenobarbital and the 52% who received diazepam, there was no difference in hospital length of stay (average length of 4.1 days for the phenobarbital group and 4.3 days for the diazepam group).
- There was also no difference in invasive mechanical ventilation use (3.1% for the phenobarbital group and 2.7% for the diazepam group).
- Further, almost all secondary outcomes—such as all-cause mortality or needing short- to intermediate-acting benzodiazepines—did not differ between the two groups.
- However, self-directed discharge was statistically more frequent among those who received diazepam (12.6%) compared with those who received phenobarbital (9.5%).
The Other Side
Some measures not included in the data may have influenced the findings, such as patients’ history of severe AWS or prior AWS complications. In addition, about half of the patients in each group received short- to intermediate-acting benzodiazepines after initiating phenobarbital or diazepam, which may have contributed to the lack of differences between the treatment groups.
Takeaway Message
“While the possibility of residual unmeasured confounding remains, the lack of observed differences in measured effectiveness or safety adds to a growing body of evidence suggesting that phenobarbital is a reasonable alternative to benzodiazepines for hospitalized patients with AWS,” the authors of an accompanying commentary wrote. “Important questions remain, however, about how best to use phenobarbital in clinical practice, including optimal dosing, the role of monotherapy versus combination therapy, and whether treatment effects differ by withdrawal severity or history of complicated withdrawal.”
Related Information
Source
Tess Bradley, et al. Comparative effectiveness of phenobarbital vs diazepam for alcohol withdrawal syndrome. JAMA Internal Medicine. Published October 12, 2026. doi:10.1001/jamainternmed.2026.4939
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