As Opioid Use Declines, Gabapentinoid Co-Prescribing Rises

The number of U.S. patients prescribed long-term opioid therapy declined from 2015 to 2023, but co-prescribing of opioids with gabapentinoids increased, prescription data showed.

In 2023, 4.2 million people had an active long-term opioid therapy episode, defined as a period of opioid dispensing lasting at least 90 days. This represents a 24.3% drop from 5.6 million people in 2015, reported Thuy Nguyen, PhD, of the University of Michigan School of Public Health in Ann Arbor, and co-authors.

Meanwhile, co-prescribing of opioids with gabapentinoids (e.g., gabapentin and pregabalin) rose substantially, from 47% in 2015 to 58.7% in 2023. Stimulant co-prescriptions increased from 5.9% to 6.7%, while benzodiazepine co-prescribing decreased from 43.8% to 33.5%.

Additionally, between 2015 and 2023, the mean age of patients with long-term opioid therapy increased from 52.5 to 60.5 years, the researchers wrote in a JAMA research letter. Commercial insurance had covered the largest share of long-term opioid therapy prescriptions in 2015 (40.9%); in 2023, Medicare was the primary payer (48.7%).

“Because older adults are at higher risk of adverse events from polypharmacy, the increased rate of co-prescribing, particularly with gabapentinoids, raises additional safety concerns,” Nguyen and co-authors wrote.

Long-term opioid therapy typically is prescribed for patients with chronic pain conditions, but has been associated with opioid misuse, overdose, and addiction.

“Our main finding is that while long-term opioid therapy has declined, it remains common among Americans. Also, co-prescribing with gabapentinoids rose between 2015 and 2023,” Nguyen told MedPage Today. “This is concerning because the FDA warns that concurrent gabapentin and opioid use may lead to respiratory depression.”

In 2016, the CDC issued guidelines to encourage prescribers to use alternatives to opioids for chronic pain. The 2016 guidance was interpreted as setting strict limits on opioid use, prompting the CDC to publish updated guidelines in 2022.

As opioid prescriptions decreased, the use of gabapentin and pregabalin — both widely prescribed off-label for a number of pain syndromes — increased. In 2019, the FDA issued a warning about respiratory problems that can occur if gabapentinoids are used alongside opioids or other central nervous system depressants. Prescribing information now includes this risk.

“Over 4 million Americans are on long-term opioids, many of whom likely suffer from chronic pain,” Nguyen said. “There is a need for ongoing commitment to evidence-informed guidelines for managing chronic pain.”

For their study, Nguyen and colleagues analyzed data from 2015 through 2023 in the IQVIA Longitudinal Prescription Database, which captured 92% of prescriptions from U.S. retail pharmacies.

A long-term episode was defined as a period of opioid dispensing lasting 90 days or longer with either a medication supply of 120 days or longer, or opioid dispensing 10 or more times within 180 days of an initial prescription, with no opioid fills in the preceding 90 days.

Researchers calculated the annual number of patients with long-term opioid therapy episodes for each year. Opioid episodes lasting longer than 1 year were counted in each year they spanned.

Patients with long-term opioid prescriptions made up 11.5% of all patients receiving any opioid therapy in 2023. The average daily dose fell from 47.9 morphine milligram equivalents in 2015 to 38.6 in 2023.

In a sensitivity analysis that defined initial prescriptions as those without opioid fills in the prior 30 days, the number of patients with long-term opioid episodes was 5.2 million, a decline of 28.6% from 7.3 million in 2015.

The study lacked information about prescribing indications, patient comorbidities, and prescriber characteristics, the researchers acknowledged. Moreover, the IQVIA database did not capture all opioid prescriptions, including those dispensed at Veterans Affairs pharmacies, they added.