Is combining Buprenorphine and Benzodiazepines hazardous?

When buprenorphine was first introduced in the US and until recently, benzodiazepines such as Xanax (alprazolam) and Valium (diazepam) were thought to be inadvisable or dangerous in patients receiving treatment with opiates, including buprenorphine, for opioid use disorders. This is an important issue because buprenorphine and methadone are widely prescribed for patients with opiate use disorders to decrease or prevent opiate cravings, relapse and overdose (called medication assisted treatment MAT). Many MAT patients are also taking benzodiazepines for anxiety disorders. The concern is that combining opiates and benzodiazepines can cause respiratory depression – a decrease in the breathing rate which can result in injury or overdose and death. https://annals.org/aim/article-abstract/2708164/next-stage-buprenorphine-care-opioid-use-disorder

Despite initial warnings about combining benzodiazepines and opiates, the FDA has backtracked somewhat in recent years and has issued statements that withholding buprenorphine from patients taking benzodiazepines might cause harm from untreated opioid use disorders. The FDA has also stated the withholding benzodiazepines from patients taking buprenorphine as part of MAT might cause might cause harm from inadequate treatment of anxiety disorders.

Although it is well known that the combination of opiates and benzodiazepines can cause respiratory depression, combining buprenorphine with benzodiazepines causes less respiratory depression than combining buprenorphine with other opiates such as morphine or methadone. Because buprenorphine is a partial agonist, it both stimulates and blocks opiate receptors. It therefore has a “ceiling effect” with respect to sedation, respiratory depression and potential overdose.

In the US buprenorphine is found in fewer that 1% to 2% of drug and opiate overdose deaths. Also, in a study done in the Boston area, patients taking buprenorphine and benzodiazapines did not have an increased risk of overdose but they did have an increased risk of accidental injury-related emergency room visits. An increase in the risk of automobile and other accidents is a well known risk of benzodiazepine use without opiates, in addition to the increased risk of benzodiazepine abuse and sleep disruption. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916951/

In another study, opioid maintenance treatment patients receiving benzodiazepine prescriptions had an increased risk of nonoverdose death but not of overdose death. It is difficult to determine from this kind of study whether the drug combination or other factors were responsible for the increase in nonoverdose death rate, so caution is still required when buprenorphine is prescribed along with benzodiazepines. https://www.ncbi.nlm.nih.gov/pubmed/28315808 Other similar studies have not shown a significant increase in adverse effects from combining buprenorphine and benzodiazepines.

In summary, simultaneous prescribing of buprenorphine and benzodiazapines is common. Anxiety disorders occur in substance use disorder patients much more commonly than would be expected by chance alone. While drug treatment of anxiety disorders should usually begin with antidepressants, many anxiety disorder patients do not respond to antidepressants alone and are then appropriately treated with benzodiazepines. When the risks of coprescribing benzodiazepines and buprenorphine are outweighed by the benefits and both physician and patient understand these risks and benefits and safer and more effective drugs are not available, benzodiazepine use may be appropriate. Many patients have taken appropriately prescribed benzodiazepines for years with significant improvement and limited or no evidence evidence of misuse or adverse effects. For such patients, tapering or discontinuing benzodiazepines may be hazardous and unrealistic. Not prescribing benzodiazepines for patients with substance use disorders and anxiety disorders whose anxiety does not respond to antidepressants may also be inappropriate.

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