Fran Lowry

December 31, 2012

AVENTURA, Florida — Increased visits to the emergency department (ED) appear to be one of the downsides to prescribing benzodiazepines to patients who are also receiving buprenorphine treatment, new research shows.

Dr. Zev Schuman-Olivier

Patients receiving buprenorphine/naloxone treatment as well as an approved prescription for a benzodiazepine had significantly more visits to the ED than those without a benzodiazepine prescription, said study investigator Zev Schuman-Olivier, MD, from Harvard Medical School, Boston, Massachusetts.

The finding is somewhat reassuring, because fatalities from benzodiazepine misuse have been a safety concern, Dr. Schuman-Olivier told Medscape Medical News.

Nevertheless, clinicians must be cautious when prescribing benzodiazepines in this population because of the increased risk for ED visits, he said.

"Benzodiazepine use and misuse during buprenorphine treatment has generated a lot of controversy among prescribers and addiction treatment programs. There have been case reports of people who have died from mixing benzodiazepines with buprenorphine, and many doctors are nervous about taking people who use benzodiazepines into their treatment programs," Dr. Schuman-Olivier added.

The study was presented here at the American Academy of Addiction Psychiatry (AAAP) 23rd Annual Meeting & Symposium.

No Drug Interactions

There has also been some uncertainty about whether prescribing a benzodiazepine for patients who suffer from extreme anxiety disorder would keep them in treatment or lead them to drop out and also whether a history of benzodiazepine misuse would affect buprenorphine treatment outcomes in some way.

To address these questions, the investigators retrospectively reviewed records of 328 patients who were in outpatient opiate treatment with regard to past-year benzodiazepine misuse and approved benzodiazepine prescription.

The researchers also had access to emergency records from the 3 hospitals serving the area where the patients lived. The nurse care managers also reported the number of ED visits in the electronic medical record.

In addition to the number of ED visits, the other primary outcomes included 12-month retention and urine toxicology testing for opioids and cocaine.

Of the 328 patients, 270 had no benzodiazepine prescription, and 58 received a benzodiazepine prescription. Additionally, 156 of the patients had a history of benzodiazepine misuse, and 172 patients had no misuse history.

Of the 58 patients who received a benzodiazepine prescription, 32 had a history of misuse, and 26 had no history of misuse.

The researchers found that there was a 40% retention rate at 12 months and that there was no association between benzodiazepine misuse and prescription on buprenorphine treatment or urine toxicology.

There were no interaction effects between benzodiazepine use and buprenorphine treatment.

ED Visits Doubled

However, they also found that benzodiazepine prescriptions were associated with more frequent visits to the ED.

Visits to the ED were 1.9 times as frequent among patients with approved benzodiazepine prescriptions compared with those without such prescriptions (P < .01).

The increase in ED visits was more pronounced in women, who had 2.7 times as many ED visits as men with a benzodiazepine prescription or women without a benzodiazepine prescription.

"Our hypothesis had been that people who got a benzodiazepine prescription and who had a history of misuse would surely have poorer retention, more opiate and cocaine use, but we didn't see this," Dr. Schuman-Olivier said.

"But we did see an elevated risk of having an ED visit due to accidental injury, due to motor vehicle accidents, bicycle accidents, traffic accidents, boiling water on yourself while cooking, from all sorts of different things. It didn't matter if you had a history of misuse or not. If you got a prescription, it increased risk."

The results of this study suggest that clinicians need to exercise a lot of caution when they prescribe benzodiazepines, because this increased risk for accidental injury not only puts the patient at risk, it puts the general public at risk as well.

"That being said, the risk of overdose, especially fatal overdose, which is what is generally discussed and talked about, is not a large effect for people who are in treatment.

"We did not show that giving a benzodiazepine to someone with severe anxiety disorder worsens their ability to function in treatment or leads to more relapse. It seems to make them about the same as everybody else from a clinical treatment perspective."

Better Assessment Needed

For Shawn Cassady, MD, from First Step, a clinic for substance abuse and dependence in Cockeysville, Maryland, the results of this study reinforce concerns about the high risk for benzodiazepine use in buprenorphine patients.

"I was surprised that a history of benzo misuse did not predict morbidity," Dr. Cassady told Medscape Medical News.

"But clearly, the prescribing of benzodiazepines in these patients increases the risk of emergency intervention. This may be due in part to an undertreated psychiatric disorder, but the larger available quantity of prescribed benzo may be a factor in future misuse and complications."

Dr. Cassady added that in his view, benzodiazepines appear to be prescribed to women for a broader range of symptoms, especially anxiety, whereas men seem more likely to be prescribed benzodiazepines for conditions such as seizures.

"Anxiety is no longer a good enough reason to prescribe benzodiazepines. We need to do a better job assessing underlying psychiatric disorders and minimizing the prescription of benzodiazepines in our buprenorphine patients."

Dr. Shulman-Olivier and Dr. Cassady have disclosed no relevant financial relationships.

American Academy of Addiction Psychiatry (AAAP) 23rd Annual Meeting & Symposium. Abstract 44. Presented December 8, 2012.