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Overlapping gabapentin and opioid prescriptions have been on the rise

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Loren Bonner

Ninety-five percent of gabapentin prescriptions are written for off-label pain management, despite studies questioning gabapentin’s effectiveness for managing pain, and reports of its misuse with simultaneous opioid therapy.

Authors of a new study published November 2022 in JAMA Internal Medicine wanted to find out how common it was for both gabapentin and opioids to be prescribed at the same time for patients. They found consistent growth in the concurrent prescription of opioids and gabapentin throughout the 13-year study period.

“While opioid analgesic episodes plateaued and eventually began to decline, gabapentin episodes continually rose and the overlap between the two increased,” said lead author Evan Peet, PhD, from the RAND Corporation. “This trend, combined with the fact that it is concentrated in high poverty, rural, and predominantly non-Hispanic white areas, suggests that this is a form of substitutionary prescribing, which is occurring in response to the opioid crisis and the associated supply-side restrictions to opioid prescribing.”

Between 2006 and 2018, Peet and his research team found that the total volume of opioid prescriptions initially rose but began to plateau before falling at the end of the observational period. In tandem, the number of gabapentin prescriptions increased 5-fold. Though the total volume of opioid prescriptions was stable before eventually falling, the number of episodes of overlapping gabapentin and opioid prescriptions more than tripled.

The research team analyzed national deidentified pharmacy claims data, capturing approximately 90% of prescriptions filled at retail pharmacies across the United States.

“While the decrease in opioid prescriptions is promising, the alarming upward trajectory of gabapentin use tempers the collective progress made in reducing patients’ exposure to opioids,” wrote authors of an accompanying editorial in JAMA Internal Medicine.

“Prescribers must recognize the risks associated with gabapentin and its limited efficacy in treating chronic pain. The sense of urgency to continue to address the opioid crisis should not override the need to find nonpharmacologic agents or other treatment modalities to manage chronic pain effectively and safely.”

A trend

Mark Garofoli, PharmD, a pain management expert, said that naturally other pain management prescription medications would replace opioid prescriptions amid the opioid epidemic and the crackdown on opioid overprescribing.

He said it was revealing in the study that pain specialists—those with the top level of pain management expertise—were shown as the highest percentage of physicians prescribing both opioids and gabapentin.

“[It] really emphasizes the reality that at some point, patients in pain need multi-modal multiple prescription treatment options,” said Garofoli, a clinical assistant professor at West Virginia University School of Pharmacy.

Additionally, the highest patient age group using both prescription opioids and gabapentin was among older adults.

The study focused only on trends, making the results simple yet strong, said Peet.

“The results are consistent with anecdotal evidence and a growing number of overdose mortalities in which both opioids and gabapentin are observed,” Peet said.

He noted that the data represent the largest and most accurate representation of these trends that have been published to date, and provide a foundation for future research exploring the causes of these trends.


According to Peet, all providers need to know the risks associated with concurrent use of opioids and gabapentin.

In many states, gabapentin is not a controlled substance and is therefore not reported to prescription drug monitoring programs. “This means that prescribers may be unaware that they are concurrently prescribing gabapentin with opioids,” said Peet.

West Virginia, one of only 7 states recognizing gabapentin as a controlled substance, started tracking gabapentin-related overdose deaths in the 2010s.

“West Virginia’s tracking of gabapentin-related deaths—key word ‘related’—does not mean that a multitude of people are overdosing solely upon gabapentin utilization, rather that gabapentin has been found in the toxicology reports of those who had a multi-drug overdose, which is very similar in concept to benzodiazepines being utilized concurrently with opioids,” said Garofoli.

Gabapentin’s mechanism of action is similar to that of other controlled substances, such as benzodiazepines and barbiturates, leading to an opportunity for misuse and abuse. Taken in combination with opioids, gabapentin increases the risk of respiratory depression and death in patients.

Garofoli pointed out that pregabalin—a “structural cousin” to gabapentin—was reclassified as a controlled substance.

“However, [a reclassification of gabapentin] would not inherently mean tightening the spigot, rather respecting the pharmacology and incorporating [that] into clinical decisions and patient care conversations,” Garofoli said. ■



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