Fran Lowry

April 22, 2014

ORLANDO, Florida ― Two medications used to help treat benzodiazepine dependence appear to have comparable efficacy but differing advantages and disadvantages, a new pilot study shows.

Results of a retrospective chart review of benzodiazepine-dependent patients undergoing inpatient detoxification showed that results with phenobarbital and a long-acting benzodiazepine were similar.

However, long-acting benzodiazepines were associated with a shorter length of hospital stay but an increased risk for hallucinations. In contrast, patients receiving phenobarbital stayed in hospital a day longer but had no hallucinations.

"There are no randomized, controlled trials comparing different treatments for detoxification in the inpatient setting," lead author Muhammad Ghazi, MD, from the University of Buffalo Medical Center, State University of New York (SUNY), told Medscape Medical News.

"We did this study because benzodiazepine codependence is a very common problem in medical practice, and we wanted to highlight that fact," Dr. Ghazi said.

"These substances are highly addictive, and ceasing them abruptly can lead to severe withdrawal symptoms, such as hallucinations, seizures, insomnia, increased heart rate and blood pressure, tremulousness, and diaphoresis, so it is important to do studies to address treatment protocols for benzodiazepine dependence in an inpatient setting. This pilot study is the first step, and the next is to do a randomized trial," he said.

The findings were presented here at the American Society of Addiction Medicine (ASAM) 45th Annual Medical-Scientific Conference.

More Research Needed

Dr. Ghazi and his team reviewed 273 charts of patients admitted to the detoxification unit at Erie County Medical Center (ECMC) for benzodiazepine dependence from January 2008 to December 2013.

Dr. Muhammad Ghazi

Of this number, 204 received phenobarbital, and 69 received a long-acting benzodiazepine.

"These are the 2 commonly used methods for inpatient detox from benzodiazepines currently used at ECMC. The patient may be switched to a long-acting benzodiazepine or phenobarbital at a comparable dose to his or her current use, and then gradually tapered down over a number of days," Dr. Ghazi explained.

A long-acting benzodiazepine taper for the treatment of benzodiazepine abuse may have its own challenges, he added. "Some research has shown that this may still cause withdrawal symptoms from incomplete cross-tolerance," he noted.

Patients in both groups were similar in age (mean age, 29 years in the phenobarbital group and 31 years in the benzodiazepine group); men made up 62% of the phenobarbital group and 57% of the benzodiazepine group, and 94% in both treatment groups were white.

Alprazolam was the most abused substance, used by 197 patients, followed by clonazepam (Klonapin, Roche), used by 126 patients.

Some patients had comorbid conditions, including hepatitis C infection, suicide ideation, insomnia, anxiety, depression, panic attacks, bipolar disorder, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, and seizure disorder.

In addition, many patients had comorbid substance abuse. Alcohol was used in 50% of the phenobarbital group and 66% of the benzodiazepine group, opioids were used in 90% of the phenobarbital group and 94% of the benzodiazepine group, and roughly half of the patients in each group used cocaine and marijuana.

Most of the patients (85% of the phenobarbital group and 83% of the benzodiazepine group) also smoked cigarettes.

The chart review found that 3% of the patients who underwent detoxification with a long-acting benzodiazepine experienced hallucinations, compared with none of the phenobarbital patients (P = .013).

The mean length of stay in the detoxification unit was shorter in the phenobarbital group (5 days) than in the long-acting benzodiazepine group (6 days), but this difference did not reach statistical significance.

Additionally, there was no significant difference between the 2 treatment groups with regard to withdrawal seizures, transfer to the intensive care unit, or readmission within 30 and 90 days.

"If you have a patient with a contraindication to using phenobarbital, then a benzodiazepine is an alternative," Dr. Ghazi said. "But really, the main conclusion is, we need a bigger sample and a randomized trial designed to see whether there is a statistically significant difference between the 2 treatments to help guide our clinical decisions."

Phenobarbital Resurgence

Commenting on this study for Medscape Medical News, Michael Miller, MD, medical director of the Herrington Recovery Center, Rogers Memorial Hospital, Oconomowoc, Wisconsin, noted that there is a resurgence of people looking at phenobarbital, especially when patients are withdrawing from benzodiazepine addiction and not just withdrawing from alcohol.

Dr. Michael Miller

"Anybody who uses phenobarb is doing evidence-based medicine, and I think it is interesting that people are trying to look at old drugs that are off patent that have efficacy," Dr. Miller, who was not part of this study, said.

"The real issue here is that clinicians are moving away from using other sedatives in this scenario and moving to anticonvulsants. I find that fascinating because, although it is easy to understand how the sedatives work, it is a little harder to understand how the anticonvulsants are working."

Dr. Ghazi reported no relevant financial relationships. Dr. Miller reported financial relationships with Alkermes and Braeburn Pharmaceuticals, Inc.

American Society of Addiction Medicine (ASAM) 45th Annual Medical-Scientific Conference. Poster 14. Presented April 11, 2014.

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