Research Highlights Risk-Benefit Analysis Around Buprenorphine with Benzodiazepines

Retention in treatment poses a significant challenge for patients receiving buprenorphine for opioid use disorder (OUD), and a new study confirms that an approach that can improve treatment engagement for some patients also carries substantial risks.

A study of Massachusetts buprenorphine patients, published in Addiction, reports that patients who were taking a benzodiazepine at the time they were on buprenorphine had an increased risk of opioid overdose and all-cause mortality compared with buprenorphine patients not on a benzodiazepine. At the same time, patients using both medications exhibited a lower risk of buprenorphine treatment discontinuation, likely resulting from the benzodiazepine working to improve their anxiety symptoms or sleep disturbance.

These results point to a difficult and prevalent problem in prescribing, with data showing that around one-third of buprenorphine patients are prescribed benzodiazepines. The study's lead author tells Addiction Professional that further research is needed to identify which patients could benefit most from using a benzodiazepine in conjunction with buprenorphine treatment, and which might bear too great a risk from that approach.

“You really need to address the comorbidities,” says Tae Woo Park, MD, a psychiatrist at Boston Medical Center's Grayken Center for Addiction. “Clinicians have got to be careful with the attitude that 'we need to stop the benzodiazepine,'” Park says, as they need to remain aware that doing so could lead to less engagement in OUD treatment for at least some patients.

Details of study

The researchers accessed several Massachusetts databases to examine outcomes for adults who received buprenorphine treatment between 2012 and 2015. They looked primarily at fatal opioid overdose among these patients, with secondary outcomes of non-fatal overdose, all-cause mortality and buprenorphine discontinuation.

In this Massachusetts sample of more than 63,000 patients, 24% had filled at least one benzodiazepine prescription during buprenorphine treatment, with benzodiazepine users more likely to be women and to have an anxiety or depression diagnosis.

There were 183 opioid overdose deaths and 693 non-fatal opioid overdoses during the study period. The rate of fatal overdoses at times when patients were receiving a benzodiazepine was three times the rate when they were receiving buprenorphine alone. Rates of non-fatal overdose and all-cause mortality during periods of receiving a benzodiazepine were around twice the rates when patients were receiving buprenorphine alone.

Park says these results are not surprising given what is known about the risk of lowered breathing and oversedation that can occur when buprenorphine and benzodiazepines are used in combination. Animal studies have shown that benzodiazepines can eliminate buprenorphine's protective respiratory “ceiling effect.”

Adjusted analyses in this sample also showed that benzodiazepine use during buprenorphine treatment was associated with a decreased risk of buprenorphine treatment discontinuation, however. “Given that anxiety and sleep disturbance has been associated with an increased risk of medication non-adherence, relief of anxiety and insomnia symptoms might promote better buprenorphine treatment adherence,” study authors wrote.

It will be important in future research to identify which patients might stand to benefit most from treatment with a benzodiazepine, Park says. It probably does not make sense to prescribe a benzodiazepine to someone unstable in his/her recovery, since that could increase the likelihood of misuse of any medication, he says. Conversely, a person with an anxiety disorder who is actively seeking help could benefit from a treatment that could relieve painful symptoms and thus possibly improve engagement in OUD treatment.

“What I think this study signals is treating anxiety and insomnia is important in improving quality of life and keeping patients in treatment,” Park says.