By Pat Anson, Editor

Another study is raising questions about the safety of the anti-seizure drug gabapentin, especially when it’s taken with opioid pain medication.

According to research published online in PLOS Medicine, combining gabapentin with opioid painkillers is associated with a significantly higher risk of dying from an opioid overdose than opioid use alone.

"Clinicians should consider carefully whether to continue prescribing this combination of products, and when deemed necessary, should closely monitor their patients and adjust opioid dose accordingly," wrote lead author Tara Gomes, PhD, principal investigator for the Ontario Drug Policy Research Network and an assistant professor at the University of Toronto.

Gomes and her colleagues analyzed data from 1,256 people in Ontario, Canada who died from opioid-related causes, and compared them with a control group of 4,619 people who also used opioid medication, but did not die of an opioid-related cause.

Overall, 12.3% of the people who died and 6.8% in the control group were prescribed gabapentin in the prior 120 days. After adjusting for additional risk factors, the researchers estimated that the combination of gabapentin and opioids was associated with a 49% higher risk of dying from an opioid overdose.

Although gabapentin is an anticonvulsant originally developed as a treatment for epilepsy, it is now widely prescribed for neuropathy and other chronic pain conditions, sometimes in combination with opioids.

Until now, no previous study had examined the risks of using gabapentin and opioid medication simultaneously, even though both are known to cause respiratory depression that can lead to an overdose.

“Our study has important implications for public health, particularly given the high degree of co-prescription. Almost 10% of patients treated with an opioid in our study also used gabapentin, while nearly half of patients treated with gabapentin were co-prescribed opioids,” said Gomes.

“Gabapentin is frequently used as an adjunct to opioids for neuropathic pain syndromes, but physicians may not be aware of the potential for respiratory depression with this drug; thus, increased awareness among patients and clinicians about the potential for a life-threatening interaction between these drugs is essential.”

The researchers believe pregabalin, an anticonvulsant that acts similarly to gabapentin, may also raise the risk of overdose when taken with opioids. But they were unable to test their theory because of the limited use of pregabalin during the study period.

Both pregabalin and gabapentin are produced by Pfizer -- under the brand names Lyrica and Neurontin -- and are two of its top selling drugs. Pfizer did not respond to a request for comment on the Canadian study.

A previous study linked pregabalin and gabapentin to an uptick in opioid overdoses in England and Wales. Some addicts believe the drugs can boost the “high” they get from heroin and other illicit substances.

Gabapentin is approved by the FDA to treat epilepsy and neuropathic pain caused by shingles. It is also prescribed “off-label” for depression, migraine, fibromyalgia and bipolar disorder. About 64 million prescriptions were written for gabapentin in the U.S. in 2016, a 49% increase since 2011.

Pregabalin is approved by the FDA to treat diabetic nerve pain, fibromyalgia, epilepsy, post-herpetic neuralgia caused by shingles and spinal cord injury. It is also prescribed off label to treat a variety of other conditions.

The CDC’s opioid prescribing guidelines recommend both pregabalin and gabapentin as alternatives to opioids, without saying a word about their potential for abuse or side effects. Pfizer has signed agreements with local prosecutors in Chicago and Santa Clara County, California to support the CDC guidelines and withdraw funding from patient advocacy groups and non-profits that question their validity.   

A recent commentary in the The New England Journal of Medicine warned that gabapentinoids -- the class of medication that Neurontin and Lyrica belong to -- are being overprescribed.

"We believe… that gabapentinoids are being prescribed excessively — partly in response to the opioid epidemic,” wrote Christopher Goodman, MD, and Allan Brett, MD. “We suspect that clinicians who are desperate for alternatives to opioids have lowered their threshold for prescribing gabapentinoids to patients with various types of acute, subacute, and chronic noncancer pain."