Phenobarbital May Top 'First-Line' Approach to Alcohol Withdrawal

Fran Lowry

December 11, 2019

SAN DIEGO ― The barbiturate/anticonvulsant phenobarbital may be a better alternative to hypnotics, specifically lorazepam, the current first-line approach, in the management of alcohol withdrawal syndrome (AWS), new research suggests.

Results of a pilot retrospective cohort study show that for patients who received phenobarbital, length of hospital stay was shorter, the 30-day all-cause readmission rate was lower, and there were fewer emergency department (ED) visits at 30 days compared to patients who received lorazepam.

Investigators led by Fadi Hawa, MD, St. Joseph Mercy Hospital Ann Arbor, in Michigan, note, "phenobarbital might be a reasonable alternative to lorazepam in the management of alcohol withdrawal syndrome patients."

The findings were presented here at the American Academy of Addiction Psychiatry (AAAP) 30th Annual Meeting.

Greater Risk for Oversedation

Approximately 1.2 million hospital admissions are related to alcohol use in the United States every year. Currently, sedative and hypnotic agents are recommended as first-line treatment to manage alcohol withdrawal, but there's no evidence to indicate that a specific agent is superior to others, Hawa told Medscape Medical News.

"In our hospital, we manage alcohol withdrawal syndrome patients using a symptom-triggered approach, called the Clinical Institute Withdrawal Assessment for Alcohol Scale [CIWA-Ar]. It allows physicians to choose between different pharmaceutical options to manage their patients, the main ones being lorazepam and phenobarbital," Hawa said.

Benzodiazepines are the preferred agents, but when Hawa and his team evaluated the five hospitals in their system, they found that some favored phenobarbital over lorazepam.

"So we took a step back and asked why this was happening. Was there a rationale for why they were using one vs the other?" Hawa said.

Initially, they conducted a literature search but found only a few randomized controlled trials that were conducted in emergency department settings and that yielded information on both drugs.

"We found that benzodiazepines are widely effective in managing this disorder but that they were also associated with a greater risk of oversedation and could be linked to agitation in patients who are medically hospitalized. So there were pros and cons to both," he said.

The investigators decided to conduct their own pilot study. They retrospectively examined the approach physicians in their own system were taking.

They reviewed the records of 606 patients aged 18 years or older who were admitted to the system between March 2016 and March 2018 with a primary diagnosis of AWS and who were treated by protocol with lorazepam (n = 543 patients) or phenobarbital (n = 63 patients).

Adjusted comparisons were conducted using propensity scoring methods. The researchers set hospital length of stay as the primary outcome.

Secondary outcomes included all-cause 30-day readmission rate, alcohol-related 30-day readmission rate, 30-day ED visits, and the need to transfer to the intensive care unit (ICU).

For patients who received phenobarbital, hospital length of stay was statistically significantly shorter than for patients who received lorazepam (2.8 vs 3.6 days; P < .001).

In addition, for the phenobarbital treatment group, the rate of all-cause 30-day readmission was statistically significant lower, at 11.11% vs 14.18% (P = .039), as was the rate of 30-day ED visits, at 11.11% vs 18.6% (P = .014).

There were no differences between the two agents with respect to alcohol-related 30-day readmission rate and the need for ICU transfers.

Caveats, Concerns

Commenting on the findings for Medscape Medical News, Thomas Penders, MD, affiliate professor of psychiatry, East Carolina University, Greenville, North Carolina, said the study reveals an important finding ― that in hospital, phenobarbital can be used as an alternative to lorazepam, with potentially better outcomes.

Dr Thomas Penders

"My experience is that physicians have their own way of doing things. The gold standard is to use a drug like lorazepam. That's what most people use, and that's where we have most of the studies," Penders said.

Some studies suggest that phenobarbital may be useful for patients who are unlikely to respond to lorazepam, so the choice could be left up to the physician, he said.

One disadvantage of phenobarbital is that it is a very long-acting drug and comes with a greater risk for respiratory depression, whereas lorazepam is very short acting and gives better control, Penders added.

"If the patient is oversedated, you just hold a couple of doses, and patients quickly recover, but with phenobarbital, it takes a much longer time to recover," he said.

Another problem with phenobarbital is that staff may not be as comfortable managing the drug or may not have sufficient experience with it, Anil Thomas, MD, director of the Addiction Psychiatry Fellowship Program at Icahn School of Medicine at Mount Sinai, New York City, told Medscape Medical News.

"Phenobarbital has its advantages and its disadvantages,'s all about the comfort of the staff. When you mention phenobarb, the nurses get a little apprehensive, whereas everyone ― every physician, every nurse ― is familiar with lorazepam," Thomas said.

Nevertheless, Thomas agreed that the shorter hospital length of stay associated with phenobarbital is a good thing.

"It is exciting, but the proper protocol for the use of phenobarbital has to be disseminated, and then staff has to be trained. The physicians in this study who used phenobarbital probably had more experience and felt comfortable and maybe had trained the nursing staff and reassured them there is nothing to worry about," Thomas said.

Lack of Experience a Hurdle

Despite the concerns voiced by Thomas and Penders, the researchers say they stand by their study findings.

Dr Linsey Gilbert

"Our hospital has an algorithm for both lorazepam and phenobarbital that tells the nurses how to dose it based on the CIWA-Ar scoring scale or how severe the patient's symptoms are, so there is information there for them to use," study coinvestigator Linsey Gilbert, DO, told Medscape Medical News.

"We do acknowledge that nurses may not be as comfortable with it if they don't use it often, but as with anything that's different, I think staff would become more comfortable with phenobarbital if they were trained and used it more often. So, lack of experience is a potential hurdle, but one we are able to overcome," she added.

"The patients that I would definitely use it in are those who have misused benzodiazepines or lorazepam ― specifically, patients with a history of escalation of care, where they have to return to the ICU. In those cases, I would certainly go to phenobarbital," Gilbert said.

Hawa, Gilbert, Penders, and Thomas report no relevant financial relationships.

American Academy of Addiction Psychiatry (AAAP) 30th Annual Meeting: Abstract 47. Presented December 08, 2019.

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