Phenobarbital shows no clear advantage over diazepam for alcohol withdrawal, large study finds
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Alcohol withdrawal is a common and dangerous medical emergency. Although benzodiazepines remain the standard treatment for this condition, the use of the barbiturate phenobarbital has increased by more than 200% in the last decade with limited evidence to suggest that this practice is safe and effective.
In the first large-scale study to compare phenobarbital to diazepam—a long-acting benzodiazepine—researchers found no differences in outcomes between phenobarbital and diazepam, potentially suggesting similar effectiveness. The findings appear online in JAMA Internal Medicine.
"Past studies have compared phenobarbital to a short-acting benzodiazepine called lorazepam and concluded that phenobarbital was better. Our study shows that when you compare phenobarbital to a similarly long-acting drug, they are actually almost equal in how well they work. This is important because hospitals are rapidly adopting phenobarbital for the treatment of alcohol withdrawal," explains corresponding author Nicholas Bosch, M.D., M.Sc., an assistant professor of medicine at Boston University Chobanian & Avedisian School of Medicine.
Comparing treatment across 754 hospitals
The researchers analyzed the health records of 24,643 adult patients across 754 hospitals in the U.S., focusing on two groups of patients who were hospitalized for alcohol withdrawal. On their first day of admission, the first group of patients was given phenobarbital while the second group of patients was given diazepam.
Because this was a look-back study of real-world data rather than a clinical trial, researchers used advanced computer programs to balance out differences between the two groups (such as age, other illnesses and overall health) to make the groups as identical as possible. They then compared how long both groups stayed in the hospital and whether they ended up needing a breathing machine, among other outcomes.
Fewer patients left against medical advice
In addition to finding similar effectiveness between phenobarbital and long-acting benzodiazepines, the researchers found that patients who received phenobarbital were less likely to leave the hospital early against medical advice compared to those who got diazepam.
"These findings may suggest differences in patient experiences between the medications, a finding that will require more research to confirm," added Bosch, a pulmonologist at Boston Medical Center.
No rush to replace diazepam
According to the researchers, this study is reassuring because it shows that hospitals have two safe and effective treatment options available.
"For doctors and health care systems, these results might mean they do not need to rush to completely replace diazepam protocols with phenobarbital, as both drugs appear to offer nearly similar benefits and risks. It also shows doctors and health care systems that have already adopted phenobarbital now have better evidence that this practice is safe and effective."
Publication details
Tess Bradley et al., Comparative Effectiveness of Phenobarbital vs Diazepam for Alcohol Withdrawal Syndrome, JAMA Internal Medicine (2026). DOI: 10.1001/jamainternmed.2026.4939
Journal information: JAMA Internal Medicine
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