Opioids and Benzodiazepines: A Deadly Combination

There are more than 14,000 deaths in the U.S. each year due to overdose of prescription opioid painkillers such as hydrocodone (HYSLINGA, NORCO, ZOHYDRO) and oxycodone (OXYCONTIN). A rapidly increasing proportion of these deaths occurs in people prescribed benzodiazepines — such as alprazolam (XANAX) and diazepam (VALIUM) — along with opioids. Misuse of this combination is a major contributor to the epidemic of fatal overdose in the U.S., because each of these two drug classes magnifies the effects of the other in producing sedation and respiratory depression.[1]

Currently, only a few Food and Drug Administration (FDA)- approved labels and patient medication guides for this large number of drugs contain specific information on the dangers of concurrent use; none contains black-box warnings.[2]

To address the lack of awareness of this public health danger, Public Citizen has helped write and has co-signed a petition to the FDA to require black-box warnings on both classes of drugs. The requested warning would state, for opioids:

WARNING: CONCURRENT USE WITH BENZODIAZEPINES REDUCES THE MARGIN OF SAFETY FOR RESPIRATORY DEPRESSION AND CONTRIBUTES TO THE RISK OF FATAL OVERDOSE, PARTICULARLY IN THE SETTING OF MISUSE.

Benzodiazepine labels would similarly warn against use with opioids. The petition also requests a medication guide for patients informing them of this risk.

Extensive evidence supporting the need for these FDA actions includes the following:

• Admissions to hospitals and addiction treatment centers for people with co-occurring addictions to benzodiazepines and opioids increased by more than five times from 2000 to 2010. (Admissions due to all other substance use decreased by about 10 percent in the same time period.)[3]
• Among 2,400 veterans with drug overdose deaths, about half occurred when veterans were concurrently prescribed benzodiazepines and opioids.[4]
• The recent rapid increase in deaths due to combining these two classes of drugs can be seen nationally and in individual states:
  • For the whole country, in 2006 about one-sixth of prescription-opioid-related deaths involved concurrent use of benzodiazepines, but by 2010, this rate had almost doubled to 30 percent.[5]
  • By 2012, in New York state, of 883 opioid-related deaths, 308 (34 percent) involved benzodiazepines.[6]
  • Data from the Rhode Island Department of Health showed that benzodiazepines were involved in 33 percent of prescription opioid fatalities from 2014 to 2015.[7]

These grim statistics, however, are not registering with prescribing doctors. According to a national database of 3.1 billion visits to primary care doctors from 2002 to 2009, 13 percent of all primary care visits involved benzodiazepine or opioid prescriptions during that interval, and concurrent prescription of benzodiazepines with opioids increased by 12 percent per year.[8]

Patients who receive opioids for chronic pain are often also prescribed benzodiazepines for associated symptoms including muscle spasms, anxiety and sleep disorder, despite little evidence for therapeutic benefit. In a national sample of chronic noncancer pain patients prescribed opioids, approximately one-third were current users of benzodiazepines.[9]

Alternative approaches include nonpharmacologic treatment for pain, such as physical therapy, massage, meditation and cognitive behavioral therapy for anxiety and sleep disorders.[10]

What You Can Do

Readers of Worst Pills, Best Pills News are aware that all benzodiazepine tranquilizers and sleeping pills, except for alprazolam and clonazepam (KLONOPIN), are now considered Do Not Use drugs, and most we have categorized as such for decades. (Alprazolam is Do Not Use except for panic disorder, and clonazepam is approved only for seizures and panic disorders.) If you are currently taking a benzodiazepine, talk with your doctor about the need to slowly taper off these drugs, since they are highly addicting and sudden withdrawal could be dangerous. In addition to the nondrug alternatives to pain discussed above, drug treatment includes acetaminophen (TYLENOL) and nonsteroidal pain medications such as aspirin and ibuprofen (ADVIL).

Examples of Available Opioid and Benzodiazepine Medications

*Other active ingredients may be present in the listed brand-name opioid products. Only opioid ingredients are listed.
**These drugs are all Do Not Use, except for alprazolam, which is Do Not Use except for panic disorders, and clonazepam, which is approved only for seizures and panic disorder.

References

[1] Wen L, Alexander-Scott N, Fracica E, et al. Citizen Petition. http://www.citizen.org/hrg2302a. Page 2.

[2] Ibid. Page 14.

[3] Ibid. Page 6.

[4] Ibid. Page 7.

[5] Ibid. Page 7.

[6] Ibid. Page 8.

[7] Ibid. Page 8.

[8] Ibid. Page 9.

[9] Ibid. Page 11.

[10] Ibid. Page 12.