Despite Decrease in Opioid Prescriptions, Rates Are Higher for Patients at High-Risk for Overdose


The likelihood that a patient would receive a new opioid prescription was higher for at-risk patients and remained true even after adjusting for demographic characteristics, comorbidities, and diagnoses associated with pain.

Joseph A. Ladapo, MD, PhD

The recent increases in opioid-related deaths in the United States has made the identification of the drivers of fatal overdose imperative, and although new data has suggested that the increase may be due to factors other than newly written prescriptions, it appears that patients at a high risk for overdose are still being prescribed opioids at a higher rate.

Led by Joseph A. Ladapo, MD, PhD, of the Division of General Internal Medicine and Health Services Research at the David Geffen School of Medicine at the University of California, Los Angeles, the research team analyzed 13,146 visits—representing the 214 million annual national visits—with a new opioid prescription, from January 1, 2005, to December 31, 2015. All visits were from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey.

The aim of identifying adults aged 20 years and older that were concurrently using a benzodiazepine—as these patients are up to 4-fold more likely to overdose compared to their counterparts in the general population.

“There’s a message here for physicians and patients—that the risks of overdose with benzos and opioids are probably underrecognized,” Ladapo told MD Magazine. “I think if you ask most doctors how much risk is involved, I don’t think a lot of them would be able to quantify it. It’s something like doubling or tripling the risk, just with co-prescription of the 2—and we’re doing a lot of that. The rates are really high, even though they declining, and opioid overdoses are still on the rise nationally.”

Data revealed that the rates of new opioid prescriptions for adults in the general population increased—non-significantly—from 78 per 1000 persons to 93 between 2005 and 2010 (rate difference, 15; 95% CI, —3 to 33; P =.10). In that same time frame, rates of new opioid prescriptions for adults using a benzodiazepine increased from 189 per 1000 persons to 351 (rate difference, 162; 95% CI, 29 to 295; P = .02).

In 2015, when opioid overdose accounted for 33,000 US deaths, the rates of new prescriptions for adults in the general population decreased to 79 per 1000 persons (rate difference, —14; 95% CI, –38 to 11; P =.28), while adults using a benzodiazepine likewise decreased to 172 per 1000 persons by 2015 (rate difference, —179; 95% CI, –310 to –48; P = .008).

“We were surprised to see how quickly the rates rose and fell, which is a good indication for the notion for the fact that these prescriptions are discretionary,” Ladapo said. “There’s a lot of latitudes here for physician judgment, and there are less risky of physical pain treatments.”

Ladapo said that an important contributor to help physicians provide better care to patients would be an understanding of the reasons for the variability in opioid prescribing. “I think we know enough to also be more proactive about policies that promote alternative therapies that are more sustainable and have good evidence, like physical therapy, occupational therapy, massage therapy, acupuncture. They are safe, effective, and sustainable with durable effects that last longer than the half-life of these medications.”

While Ladapo admitted he was uncertain about the willingness of established, or older, physicians to utilize an alternative to controlled substances like opioids, he did note that in his experience, there is an openness to them among the younger physicians he’s worked with. Additionally, as the opioid epidemic continues to plague the United States, he said there is a lesson to be learned from other national issues.

“I think there are a lot of patients that want to [avoid opioids], but I’ve also had patients who want a rapid solution. This has been a national issue with inappropriate antibiotic prescriptions as well. One thing we could take a lesson from there has been that when patients actually know why we don’t want to prescribe these things, they actually—and research shows it—are more likely to agree with the physician’s decision to avoid the antibiotic,” he said. “There’s something to be said there for that strategy, to share with the patient why it’s a concern to prescribe an opioid. But even that’s not completely effective, and it’s up to the doctor to make that decision—it’s not an easy thing to do.”

The data showed that ultimately, the likelihood that a patient would receive a new opioid prescription during an ambulatory visit remained higher for patients concurrently using benzodiazepines compared with the general population (unadjusted relative risk, 1.74; 95% CI, 1.45-2.09; P <.001). This remained true even after adjusting for demographic characteristics, comorbidities, and diagnoses associated with pain (adjusted relative risk, 1.83; 95% CI, 1.56 to 2.15; P <.001).

Perhaps one of the more notable findings was that naloxone (Narcan), the antidote to opioid overdose, was co-prescribed in less than 1% of visits when a patient concurrently used a benzodiazepine.

“It was a surprise to see no one was prescribing Narcan—the rates were really low,” Ladapo said. “We were looking at initial prescriptions, and the decision-making process about the correct candidates are still up in the air, but especially in light of the recent surgeon general’s statement, it was surprising.”

“The [overdose] rates are going up, and it’s tragic, and we’ve contributed as physicians. It’s important to try to rectify without causing more patient harm,” he added.

The study, “Physician Prescribing of Opioids to Patients at Increased Risk of Overdose from Benzodiazepine Use in the United States,” was published in JAMA Psychiatry.

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