Last month the FDA (Food and Drug Administration) announced their decision to require black box warnings on opioid and benzodiazepine prescribing information. This warning will state that co-prescribing these two classes of medications increases the risks to patients of death, coma, sleepiness, and respiratory depression. The FDA also said they would require medication guides for patients, describing these risks.
Black box warnings are the strongest warnings issued by the FDA. These warnings are literally placed in a bold black box at the top of the prescribing, where the information is most noticeable.
I applaud the FDA’s action. I think FDA’s statement will make physicians and other providers think twice before blithely writing a benzodiazepine prescription for a patient already prescribed opioids. A black box means, “Take this seriously!”
Ten years ago, co-prescribing of opioids and benzodiazepines was commonplace for primary care physicians in my area. Earlier this year, our state medical board announced they would investigate the top prescribers of opioids and benzodiazepines together. Since then, I have noticed some prescribers appear to be backing away from the routine prescribing of benzodiazepines..
Most opioid treatment centers have policies in place to address benzodiazepine use, both licit and illicit. There are still a few OTPs who approve benzodiazepines to be prescribed for methadone or buprenorphine patients, but I think they are in the minority. Most opioid treatment program physicians feel that besides the dangers of sedation and overdose, there are few medical indications for long-term (more than three months) benzodiazepine prescriptions, and much better long-term treatments for anxiety disorders.
An article In the April 16th, 2016 issue of the American Journal of Public Health underlined how important it is to evaluate benzodiazepine prescribing in the U.S., particularly when prescribed along with opioids. 
The authors begin the article by stating that benzodiazepines were found to be involved in nearly a third of opioid overdose deaths in 2013. The authors wished to investigate nation trends in benzodiazepine prescribing and in fatal overdoses involving benzodiazepines.
The authors found the percentage of U.S. adults filling benzodiazepine prescriptions increased significantly over past years. They also found that among people who filled benzodiazepine prescriptions, the amount, defined as lorazepam equivalent doses, also increased significantly. Simultaneously, overdose deaths rates involving benzodiazepines rose nearly four-fold, though deaths appear to have plateaued since 2010.
Another study, this time in Canada, evaluated the risk of death in polysubstance users. In a prospective cohort study of IV drug users, done from 1996 through 2013, benzodiazepine use was more strongly associated with death than any other substance of abuse. [2
Many patients ask why they can’t take benzodiazepines while on methadone or buprenorphine. I tell them I’m mainly worried about the increased risk for overdose death, but I also tell them benzodiazepines are over-prescribed. Prescribing information suggests benzodiazepines are most beneficial when prescribed for no more than three or four weeks. Long-term prescribing of benzodiazepines is generally discouraged, due to serious side effects seen even in patients with no substance use disorders.
Benzodiazepines are associated with increased risk of auto accidents, increased risk of completed suicide, worsening of mood disorders like depression, increased risk of drug-induced dementia, and increased risk of daytime fatigue. Benzodiazepines are also associated with increased risk of cancer, falls, and pneumonia.
Although an association of benzodiazepines with these conditions doesn’t necessarily mean benzodiazepines cause these conditions, it’s a good reason to be conservative when prescribing benzodiazepines and other sedatives, pending further studies.
Sedative medications including benzos can make undiagnosed sleep apnea worse, even to the point of causing death. Obesity increases the risk of sleep apnea, and with more adults becoming obese, the risks of benzodiazepines in such patients may be overlooked.
As for my patients, many of whom are prescribed methadone or buprenorphine, the risk of drug interaction and overdose with the hypnotics usually outweighs all of the benefits, and I recommend that patients do not mix these two types of medications.
- Bachhuber et. al., “Increasing Benzodiazepine Prescription and Overdose Mortality in the Unites States, 1996-2013,” American Journal of Public Health, April 16, 2016.
- Walton et. al., “The Impact of Benzodiazepine Use on Mortality Among Polysubstance Users in Vancouver, Canada,” Public Health Rep., 2016 May-June;13(3)491-9.