Phenobarbital has some ideal properties for the treatment of alcohol withdrawal. In particular, it has a long half life (about 100 hours) allowing for a single dose without the requirement for prescriptions.
However, there are some genuine safety concerns especially if they are mixed with other drugs or alcohol. And there is little high-quality evidence to support it’s use in patients being sent home from the ED.
This is a retrospective chart review of patients discharged from a single ED in California over a three-year period with a discharge diagnosis of alcohol withdrawal. Patients were stratified into three categories; those who got benzo’s, benzo’s plus phenobarbital or just phenobarbital alone.
The primary outcome was return ED encounter within 3 days of the index visit. (Yes, this is an odd primary outcome, but it was chosen for pragmatic purposes as below...)
470 patients were included. 235 got benzo’s, 133 got phenobarbital, and 102 got the combination special.
Treatment with phenobarbital (alone or in combination) was associated with a decreased odds ratio of a return ED visit within 3 days. (AOR 0.45 95% CI 0.23, 0.88 and AOR 0.33 95% CI 0.15,0.74 respectively).
The cynic in me wonders if this is because phenobarb patients died… (But this was probably not the case as the author were eventually able to account for most patients)
It is interesting to note that patients who received phenobarbital got much more GABA agonist medication than those that simply got benzodiazepines. Four times as much was given if you adjust for drug equivalence. Perhaps this is why they were less likely to return?
Unfortunately, this paper does not address the big question of safety. It would take a much larger study with more robust methodology (that avoids loss to follow-up) to answer this. And such a study would be very difficult to undertake as this cohort of patients are unreliable and not likely to be compliant with study protocols etc.
What’s the take home message?
Phenobarbital for the outpatient treatment of alcohol withdrawal is tempting, but there is arguably not enough evidence to support its routine use.
Lebin A, Mudan A, Murphy CE, et al. Return Encounters in Emergency Department Patients Treated with Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal. J Med Tox. 2022;18:4-10. [link to full text of article]