Patient Outcomes Associated With Phenobarbital Use With or Without Benzodiazepines for Alcohol Withdrawal Syndrome: A Systematic Review.

Purpose: Benzodiazepines are the drug of choice for alcohol withdrawal syndrome (AWS); however, phenobarbital is an alternative agent used with or without concomitant benzodiazepine therapy. In this systematic review, we evaluate patient outcomes with phenobarbital for AWS.

Methods

Medline, Cochrane Library, and Scopus were searched from 1950 through February 2017 for controlled trials and observational studies using ["phenobarbital" or "barbiturate"] and ["alcohol withdrawal" or "delirium tremens."] Risk of bias was assessed using tools recommended by National Heart, Lung, and Blood Institute.

Results

From 294 nonduplicative articles, 4 controlled trials and 5 observational studies (n = 720) for AWS of any severity were included. Studies were of good quality (n = 2), fair (n = 4), and poor (n = 3). In 6 studies describing phenobarbital without concomitant benzodiazepine therapy, phenobarbital decreased AWS symptoms (P < .00001) and displayed similar rates of treatment failure versus comparator therapies (38% vs 29%). A study with 2 cohorts showed similar rates of intensive care unit (ICU) admission (phenobarbital: 16% and 9% vs benzodiazepine: 14%) and hospital length of stay (phenobarbital: 5.85 and 5.30 days vs benzodiazepine: 6.64 days). In 4 studies describing phenobarbital with concomitant benzodiazepine therapy, phenobarbital groups had similar ICU admission rates (8% vs 25%), decreased mechanical ventilation (21.9% vs 47.3%), decreased benzodiazepine requirements by 50% to 90%, and similar ICU and hospital lengths of stay and AWS symptom resolution versus comparator groups. Adverse effects with phenobarbital, including dizziness and drowsiness, rarely occurred.

Conclusion

Phenobarbital, with or without concomitant benzodiazepines, may provide similar or improved outcomes when compared with alternative therapies, including benzodiazepines alone.