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Prescribing practices that increase risk of opioid overdose


Two studies, one from Prime Therapeutics and Stanford, reveal an alarming increase in overdose with concurrent use of opioids and benzodiazepines. Here’s how managed care can help.

Concurrent opioid and benzodiazepine use is prevalent and needs to be addressed, according to two recent studies.

study published in the British Medical Journal (BMJ), found that the simultaneous use of opioids and benzodiazepines, primarily used to treat anxiety and insomnia, has been increasing over the past decade, despite well known risks of this combination.  


Researchers at the Stanford University used a dataset of healthcare claims for more than 300,000 privately insured patients. Using these data, they tracked the simultaneous use of benzodiazepines and opioids between 2001 and 2013, as well as the incidence of emergency room visits and hospital admissions for opioid overdose during this time

“We found that, in our study population, the simultaneous use of both drugs accounted for about 15% of ER visits/hospital admissions for opioid overdose,” according to lead author Eric Sun, MD, PhD, assistant professor, department of anesthesiology, perioperative and pain medicine, Department of Health Research and Policy, Stanford University.

“This study is important for managed care executives because one reason why the growth in the use of both drugs may have increased-despite widespread knowledge of the risks-is that information on a given patient's prescriptions is quite fragmented,” Sun says. “Typically, it is difficult for one physician to know what another [physician] is prescribing; the only way to figure this out is to rely on the patient. However, insurers are in a position to know all the medications a patient has been prescribed. Indeed, our study used healthcare claims data." 

Thus, according to Sun, managed care executives may be uniquely positioned to reduce the incidence of this and other potentially dangerous drug combinations by utilizing claims-based surveillance and monitoring systems and alerting physicians and patients of the concern. The BMJ published an editorial on Stanford’s research, which echoes this point.

Next: Another study


 Prime Therapeutics study

During 2015, Prime Therapeutics studied pharmacy claims data from approximately 19 million commercial members aged 18 years or older. They analyzed those members with two or more opioid claims filled on two or more separate days with a 15 days supply or more (buprenorphine/naloxone combination products were excluded while opioid containing cough/cold products were included). Members were also required to have two or more benzodiazepine claims on two or more separate days.

Buprenorphine/naloxone combination products were excluded and opioid containing cough/cold products were included. Members were also required to have two or more benzodiazepine claims on two or more separate days.

Concurrent use of opioids and benzodiazepine was defined as 30 or more cumulative days of overlap based on days supply found on the claims. Using medical claims data, concurrent use was also examined after excluding members with one or more medical claims with a cancer diagnosis code in 2015.


Prime found 17% of commercially insured adult opioid utilizers without cancer used opioids and benzodiazepines concurrently for 30 days or more. The rate of concurrent opioid and benzodiazepine was alarmingly high at 0.9%, or 1 per 100 members, according to Cathy Starner, PharmD, principal health outcomes researcher, Prime.

“Although the methods are different, and Prime did not examine the associated opioid overdose events, our research relates [to the BMJ study] because it has a similar goal-to identify the prevalence of concurrent use and highlight the need to create programs that can reduce the risk of adverse effects from the misuse of opioids and benzodiazepines together. It is important for providers to understand there is a problem, and it’s not only a problem in the older adult population,” Starner says. 

Addressing the problem

One way to the address the problem is through implementation of pharmacy benefit clinical programs, according to Starner. “Advanced knowledge around prevalence of concurrent opioid and benzodiazepine use can help insurers plan for potential quality measures or other prescribing restrictions to improve member safety. Our nation is in an opioid crisis, and several prominent national organizations and federal agencies have expressed concern and provided guidance against concurrent use of opioids and benzodiazepines use. So now is the time to enhance, create and improve clinical programs aimed at safe and appropriate controlled substance use,” she says.

Based on these studies, Sun and Starner offers these eight rommendations for health plan executives:

1. Examine your company’s controlled substances policies and programs. “The concern is not only with the opioids,  but with all controlled substances, including but not limited to opioids and benzodiazepines. The Drug Enforcement Agency has classified them as controlled substances for a reason; these drugs have a high potential for abuse, dependence and harm,” Starner says.

2. Do not stop with the Medicare population. “Concurrent opioid and benzodiazepine use is also occurring in our commercially insured population and reducing risk for this population is equally important,” she says.

3. Implement system-wide approaches aimed at monitoring the use of both of these drugs then alert patients (and their prescribers) who are using both drugs concurrently, according to Sun.

4. Begin or enhance current clinical programs aimed at controlled substances misuse. One example is using prescriber letters. This is an inexpensive yet effective method for increasing awareness of potential controlled substance misuse and decreasing the prevalence, according to Starner

5. Implement pharmacist consultation, which has been shown to reduce controlled substance misuse/overuse. 

6. Consider identifying at-risk members and developing clinical programs with the goal of reducing combination use. “As the CDC recommends against combination opioid and benzodiazepine use, and the Pharmacy Quality Alliance has developed a pharmacy performance measure, it is anticipated that health insurers’ quality of care will be assessed based on the prevalence of combination use among their membership,” Starner says.

7. Understand your own data and member use patterns to determine intervention thresholds of concurrent opioid and benzodiazepine use. 

8.  Don’t stop here. “Future research should continue to include examination of prescribers with high volumes of concurrent opioid and benzodiazepine users within their discipline,” Starner says. “Using a variety of methods to identify misuse and abuse will enhance our ability to make change and improve member safety.”  

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