Most prescriptions for the medication gabapentin are for unapproved uses—and many patients end up taking it along with drugs that create potentially dangerous interactions.

That’s the conclusion of a new study that looked at “off-label” use of gabapentin. In the United States, the drug is officially approved for treating certain seizures and some forms of nerve pain.

It’s known, however, that gabapentin is commonly prescribed for other uses, including various types of pain conditions and psychiatric disorders like depression and anxiety.

The new study highlights just how widespread that off-label use is: Of almost 130 million outpatient visits where gabapentin was prescribed, more than 99% were for off-label uses.

“We anticipated there’d be a lot of off-label use,” said senior researcher Amie Goodin, an assistant professor at the University of Florida College of Pharmacy.

Even so, she said, it was surprising to see the magnitude of that use.

And one-third of the time, patients prescribed gabapentin off-label were also on a medication that can depress the central nervous system.

That’s a concern because in 2019, the U.S. Food and Drug Administration issued a warning about combining gabapentin with central nervous system (CNS) depressants, saying sedation and serious breathing problems can result. The warning was particularly aimed at people with risk factors for depressed breathing—including the elderly and people with lung diseases like emphysema and chronic bronchitis.

“CNS depressant” is a broad term, Goodin said. It includes drugs ranging from antidepressants and anti-anxiety medications, to antihistamines, to muscle relaxants.

This study looked at prescriptions made between 2011 and 2016—before the FDA safety warning.

But, Goodin noted, at the time there was another reason for careful prescribing. Starting in 2008, gabapentin and other anti-seizure drugs were required to carry a warning about an association with increased risk of suicidal behavior.

“Gabapentin does have a reputation as a safe drug to try,” Goodin said. “But there is some risk.”

She recommended that people who are on the drug talk to their pharmacist about any safety concerns, especially if they are simultaneously taking other medications.

People will not necessarily know if they are taking a drug that is a CNS depressant, according to Bethany DiPaula, a professor at the University of Maryland School of Pharmacy.

Like Goodin, she noted that it is a broad category, and not every antidepressant or every anti-anxiety medication will fall into it.

DiPaula, who was not involved in the study, agreed that patients on gabapentin should take any questions to their pharmacist or the health care provider who prescribed it.

In general, DiPaula said, people should be sure all of their health care providers know which medications and supplements they are taking.

“And ideally,” she said, “you should get all of your prescriptions from the same pharmacy.”

For the study, Goodin and UF graduate student Brianna Costales used data from a federal survey that collects de-identified information on outpatient doctor visits nationwide.

Out of more than 200,000 patient records, just over 5,700 involved a gabapentin prescription. That corresponds to nearly 130 million visits nationally between 2011 and 2016.

The vast majority of those prescriptions were off-label, and most patients were also on other prescription drugs. In nearly one-third of cases, those additional medications included a CNS depressant.

Antidepressants were the most common type of CNS depressant, followed by opioid painkillers and benzodiazepines.

Of all office visits where off-label gabapentin was in the record, about 5% of patients had a depression diagnosis, and 3.5% had an anxiety disorder.

It’s not clear, Goodin said, whether the gabapentin was prescribed specifically for those mental health disorders. There is a lot of crossover between pain and depression/anxiety, so it’s possible the drug was prescribed for pain in at least some of those patients.

In general, Costales noted, there is little clinical trial evidence to support gabapentin for psychiatric conditions.

DiPaula said it is always wise for patients to make sure they understand exactly why a drug is being prescribed, and what the potential side effects are.

It’s also important, she added, for patients to periodically review all of their medications with their provider, in part to talk about whether they are all still needed.

“De-prescribing”—either lowering a drug dose or stopping it altogether—is as important as adding new medications, DiPaula said.

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