Co-Prescribing of Opioids and Gabapentinoids Grows Despite Warnings
/By Pat Anson
In 2019, the FDA warned that serious breathing problems can occur in patients who take gabapentinoids with opioids or other medications that suppress the central nervous system. The agency said elderly patients and those with pre-existing lung problems were at highest risk of respiratory depression, which can lead to a fatal overdose.
Those warnings went unheeded by many doctors, according to a new study that found the co-prescribing of gabapentinoids to patients on long-term opioid therapy increased over the past decade, rising from 47% in 2015 to 58.7% in 2023.
Gabapentinoids are a class of nerve medication originally developed to prevent seizures, but are widely prescribed off-label to treat pain. They include gabapentin (Neurontin) and pregabalin (Lyrica), as well as generic versions of the drugs.
Not only did co-prescribing with gabapentinoids increase, but the age of patients on long-term opioids also rose, from 52.5 years in 2015 to 60.5 in 2023. Nearly half of those patients (48.7%) are on Medicare.
“Because older adults are at higher risk of adverse events from polypharmacy, the increased rates of coprescribing, particularly with gabapentinoids, raises additional safety concerns,” said Thuy Nguyen, PhD, Assistant Professor of Health Management and Policy at the University of Michigan’s School of Public Health.
Nguyen and her colleagues' findings, published in a JAMA research letter, also document a steady decline in long-term opioid use, which coincides with federal and state guidelines that were imposed to limit opioid prescriptions.
Between 2015 and 2023, the number of U.S. patients on long-term opioid therapy for at least 90 days fell from 5.6 million to about 4.2 million — a 24.3% decrease.
At the same time, the average daily dose of opioids also declined, from 47.9 morphine milligram equivalents (MME) in 2015 to 38.6 MME in 2023 – which is in line with CDC guidelines that recommend caution when doses exceed 50 MME.
Researchers think more work is needed to reduce opioid use and to find alternative ways to relieve pain.
“With almost 5 million Americans on long-term prescription opioids for chronic pain, and likely millions more who are taking shorter courses of prescription opioids for acute pain, most clinicians are likely to care for someone using prescription opioids for pain, highlighting the pressing importance for investing in better treatment models for pain,” said senior author Pooja Lagisetty, MD, Associate Professor of Internal Medicine at the University of Michigan Medical School.
In addition to gabapentinoids, researchers tracked overlapping prescriptions for other controlled substances. They found that co-prescribing of long-term opioids with benzodiazepines declined from 43.8% in 2015 to 33.5% in 2023; while co-prescribing for stimulants rose from 5.9% to 6.7%.
In short, polypharmacy is relatively common with patients on long-term opioids, despite the known risks of combining certain drugs.
Common side effects from gabapentin include brain fog, dizziness, weight gain, headache, fatigue, and anxiety. The drug has also been linked to a higher risk of dementia.
Those side effects may lead to a “prescribing cascade,” in which doctors mistakenly prescribe unnecessary medications to patients that cause even more side effects – never suspecting that gabapentin was the cause and they should consider discontinuing the drug.
In 2024, gabapentin was the fifth most prescribed drug in the U.S., with prescriptions nearly tripling since 2010. The number of patients prescribed gabapentin reached 15.5 million in 2024.
The off-label prescribing of gabapentin is legal and, in some cases, appropriate. But it has reached extreme levels, with studies estimating gabapentin is prescribed off-label up to 95% of the time.
