Dr. Michael Kilkenny tracks gabapentin as part of his years-long effort to reduce drug overdose deaths in hard-hit Cabell County, W.Va. Photo courtesy of the Cabell-Huntington Health Department
WASHINGTON, Aug. 8 (UPI) -- Gabapentin, a widely prescribed drug for pain, has caused such concern about its link to fatal opioid overdoses that two major federal agencies have warned patients, doctors and healthcare facilities about the potential for abuse.
In December 2019, the Food and Drug Administration required new label warnings about the risk of serious breathing difficulties that could lead to death in people using gabapentin's class of drugs in combination with opioid pain medicines.
And the Centers for Disease Control and Prevention cautioned May 13 that nearly 90% of drug overdose deaths in which gabapentin was detected also involved an opioid: "particularly and increasingly" illicit fentanyl.
Then, on June 28, the CDC, in a popular medical journal, cited mounting concern over postmortem toxicology test data that detected gabapentin in almost 1 in 10 U.S. overdose deaths between 2019 and 2020.
Though it was originally approved in 1993 as an anti-convulsant medication and also OK'd by the FDA to treat a painful complication of shingles, gabapentin's liberal prescribing has turned into a growing epidemiological threat.
In 2019, the latest year for which data are available, 69 million prescriptions were dispensed in the Unites States, making it the seventh most commonly prescribed medication nationally, according a paper published in CDC's May 13 Morbidity and Mortality Weekly Report.
For Dr. Michael Kilkenny, the top public health official in Cabell County, W.Va., the figures provided a grim reminder of the overdose deaths tied to gabapentin he has seen.
The economically depressed county, nestled in the state's northwest corner, received international news coverage in August 2016, when 26 area residents experienced nonfatal drug overdoses within a four-hour period.
"Virtually every person in our community knows someone who has died of an overdose," and the problem includes people "from all walks of life," Kilkenny told UPI in a phone interview.
"We love all of our people in Huntington, whether they're completely well, whether they have heart disease or substance use disorder," he said.
Kilkenny has worked on the problem for years, tracking gabapentin's presence in postmortem toxicology reports on multi-drug overdose fatalities. He said he knows gabapentin is making a bad situation worse.
Gabapentin was involved in 10 of 134 overdose deaths in Cabell County in 2016; six of 202 such deaths in 2017; four of 151 in 2018; and three of 113 in 2019, he said.
Kilkenny said the county reduced drug overdose deaths by 40% from 2017 to 2019. But the numbers crept back up when the disruptive COVID-19 pandemic hit in 2020.
"Any time we see something that makes [the drug overdose situation] worse, we have to take action on that -- and gabapentin has met that threshold," Kilkenny said.
He and other medical experts said gabapentin often is used with illicit synthetic opioids -- including fentanyl, which the CDC says is up to 50 times stronger than heroin and 100 times stronger than morphine.
More intense high
Gabapentin is so attractive to drug users because it "potentiates" the opioid, making the high more intense or more frequent. But the combination may cause dangerous sedation and respiratory depression, or slowed, ineffective breathing, and lead to death, principal author Christine Mattson wrote in the May 13 CDC article.
If a person with an acutely painful condition, who is alert, breathing well and able to describe their condition enters the emergency department at Ohio State University's Wexner Medical Center in Columbus -- about 100 miles north of Huntington, W.Va. -- they might receive a low dose of gabapentin.
This will be done once -- usually a combination of 300 milligrams of gabapentin along with non-opioids, said Dr. Emily Kauffman, Wexner's director of emergency addiction services.
"But we don't prescribe gabapentin 'to go,'" she said. "Most of this gabapentin, I think, is being prescribed in the outpatient clinics" by pain specialists.
While the need for pain relief is understandable, Kauffman said clinicians must keep a close watch, especially because the opioid-gabapentin combination may be deadlier in older adults and people with chronic medical conditions, such as kidney disease or sleep apnea.
"Gabapentin is a great medicine. However, it must be used cautiously," Kauffman said.
Can help addicts
Though concerns about the drug's use are growing Dr. O. Trent Hall, assistant professor and addiction medicine physician in Ohio State's Department of Psychiatry and Behavioral Health, told UPI that gabapentin is useful in certain situations as a part of an addiction treatment program.
"It is helpful in reducing restlessness during alcohol and opioid withdrawal," he said in an email. "There is mixed, low-quality evidence it may be helpful for some people trying to stop cocaine."
Gabapentin also is offered off-label in combination with naltrexone or acamprosate "to help people in early recovery from alcohol use disorder who have anxiety as a trigger for drinking," Hall said.
Drugs that are dispensed off-label are not FDA-approved for the condition being treated, but have shown effectiveness in combatting that condition.
Since its FDA approval in 1993, gabapentin has evolved into a medication prescribed for off-label uses the vast majority of the time, medical and pharmacy experts said.
The American Pharmacists Association's journal, which disseminates information for pharmacy professionals to improve medication use, reported last October that gabapentin had landed on Schedule V controlled substance lists in seven states and been placed in another dozen states' prescription drug monitoring programs.
Schedule V drugs have the least potential for abuse among controlled substances and are used generally for antidiarrheal, antitussive and analgesic purposes, according to the Drug Enforcement Administration.
Public Citizen involved
Because of what it views as gabapentin abuse, Washington-based Public Citizen filed a petition in February with the FDA and DEA, seeking additional safeguards that include better tracking of its use and limitations for use.
The non-profit group wants to accomplish this by having the drug listed as a Schedule V drug nationally because "substantial evidence of widespread abuse" exists, largely as the result of "extraordinary levels of off-label prescribing," the petition says.
On Thursday, the FDA responded, saying it "has not yet resolved the issues" raised in the petition.
"FDA has been unable to reach a decision ... due to the need to address other agency priorities," wrote Carol Bennett, deputy director of the Office of Regulatory Policy in the agency's Center for Drug Evaluation and research. She basically said stay tuned.
Out West, Dr. David Spencer, professor of neurology at Oregon Health & Science University in Portland, told UPI that as an epilepsy specialist, he prescribes gabapentin occasionally for treating seizures, but sometimes must prescribe relatively high doses because it is not that potent otherwise.
He said he sees gabapentin prescribed much more often for other indications, primarily for treating neuropathic pain or at times for its anti-anxiety effects.
"There is a general perception that gabapentin is a relatively benign drug, because it is generally well-tolerated, has been in use for a long time and has few known drug-drug interactions," Spencer said in an e-mail.
However, he said, "The emerging information about the association with opioid-related deaths runs counter to this perception, and it may not be intuitive to many clinicians to consider that there may be important safety issues with its use."