A University of Minnesota pharmacist is raising concerns about the rising use of a class of painkillers called gabapentinoids and the influence of pharmaceutical company payments on the way doctors prescribe the pills.

Analyzing federal prescription data, Greg Rhee and his colleagues reported Monday that doctors were more likely to prescribe higher-cost, brand-name gabapentinoids when they received payments or other financial support from the companies that manufacture those drugs.

"The rise in gabapentin prescribing is concerning because this drug class has the potential to be abused," said Rhee, who is an adjunct U professor but is based in Connecticut. "The findings also raise a concern about why physicians prescribe brand-name drugs when less-expensive generic alternatives are available in the market."

Gabapentinoid use tripled between 2002 and 2015. The drug is primarily used to treat fibromyalgia, seizures and nerve pain, but a team of international researchers reported earlier this year that it also comes with a higher rate of suicidal behaviors, unintentional overdoses and traffic accidents.

Rhee said the drugs are not as addictive as opioid painkillers, but that it is still important to understand why they are being prescribed more frequently, and whether any influences beyond the needs of patients are playing a role.

"If gabapentin is misused or abused, it could be a second case of the opioid crisis," said Rhee, referring to the alarming increase in prescriptions, overdoses and deaths from common opioids such as oxycodone and more potent forms such as fentanyl.

According to his study in JAMA Internal Medicine, three manufacturers of brand-name gabapentinoids made payments of $11.5 million to more than 50,000 doctors between 2014 and 2016. Those doctors were almost twice as likely to prescribe brand-name versions compared to other doctors who prescribed some form of gabapentinoids but received no payments.

Gabapentinoids are a class of drugs that include gabapentin, which was federally approved in 1993 under the brand name Neurontin for treatment of seizure disorders and nerve pain. Another form is pregabalin, approved in 2004 under the brand name Lyrica. The drugmaker Pfizer created both Neurontin and Lyrica. Other brand name forms of the drugs include Gralise, Gabaron and Horizant.

Marketing boosts sales

Rhee's study adds to the evidence showing an association between the money that drugmakers spend on doctors and the prescribing patterns of those doctors. A second study in the same journal showed a relationship between drug company payments and doctors' prescribing of high-cost biologic agents for inflammatory bowel disease.

"All of these studies have essentially the same finding — that marketing to physicians is associated with increased sales of a company's product and increased Medicare expenditures," Dr. Robert Steinbrook, the journal's editor-in-chief, said in a letter accompanying the studies. While the studies don't account for other influences on prescribing behavior, or the fact that certain patients might benefit more from brand-name drugs, Steinbrook said, "the pattern is indisputable.

Marketing to physicians is widely blamed for the opioid crisis because industry-funded campaigns two decades ago convinced doctors that pain was a vital sign that warranted treatment, and that they would lose patients if they didn't prescribe opioids.

Now researchers fear that doctors will give gabapentin off-label — beyond conditions for which it has been approved — for unproven treatment of pain because they are curbing their opioid prescriptions.

PhRMA, the trade group for brand-name drug manufacturers, updated its code of conduct in 2017 to emphasize that marketing to doctors must focus on scientific benefits of medications.

Minnesota had an unwitting hand in unmasking the association between marketing and physician prescribing. The state's Board of Pharmacy for years had a unique requirement that drugmakers report how much they paid Minnesota doctors in speaker fees, lunches and other compensation. But the unwieldy paper records went largely ignored until 2007, when researchers and journalists first examined and published the data.

Now, the federal Medicare program publishes comparable national data on its Open Payments website and allows users to search for specific doctors from across the country.

The data shows that Minnesota doctors received proportionately fewer payments from manufacturers of brand-name gabapentinoids compared to colleagues in states such as Ohio, New York and California.

Beyond fueling addictions, Rhee said excessive prescribing raises cost concerns because a one-month supply of brand-name gabapentinoids can cost hundreds of dollars, whereas generic gabapentin costs about $20.

Some Minnesota health plans already have policies in place to address the cost. HealthPartners' PreferredRX formulary for its health plans, for example, has a "step therapy" requirement for patients to try other drugs first before receiving higher-cost Lyrica.