Gabapentin the Placebo of Pain Medications

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https://www.vice.com/en_us/article/j5y4py/millions-use-gabapentin-for-anxiety-and-pain-but-little-evidence-it-works

This article is reprinted in part from an Oct 31, 2019 article on Vice by Shayla Love. To read the full article, follow the link above.

Gabapentin is approved for treating seizures and nerve pain, yet 95 percent the time it’s used for other conditions, without strong research to back it up. With recent links to overdose and reports of suicide, why is it still being used so much?

When Mary’s grandmother had her leg amputated at the knee, doctors prescribed gabapentin for her phantom leg pain.

“I remember thinking that was super weird,” Mary said, because she herself had a prescription for gabapentin too. Mary is 28, and has been taking the drug, a generic medication also sold as Neurontin, for nearly a decade. Her doctor gave it to her to balance out the effects of her ADHD medication, Concerta. “Why was something I was taking to take the edge off an ADHD drug also being given to an amputee?” she wondered.

Indeed, the Food and Drug Administration hasn’t actually approved gabapentin for either of those uses—gabapentin is approved for treating seizures and nerve pain that can happen after shingles. Yet its reach extends much, much further. A person might receive it for migraines, fibromyalgia, hot flashes, depression, bipolar disorder, restless leg syndrome, anxiety, and a wide variety of other nerve and chronic pain issues. It’s even given to cats and dogs with chronic pain.

“It’s the ‘let’s just throw something at the wall and hope that it magically sticks’ drug,” said Jordan Covvey, an assistant professor of pharmacy administration at Duquesne University School of Pharmacy. “There’s a lot of damage that could be happening with that sort of strategy.”

Treating conditions like chronic pain, depression, or anxiety is hard. The medications doctors have to offer can come with side effects, the potential for misuse, and sometimes they just plain don’t work. Gabapentin has been considered relatively safe, and its broad effects on the brain mean, theoretically, that it could help a wide variety of disorders. It’s said to have a calming effect and touted as non-addictive. As a result, it is often the drug of choice when Plans A, B, or C don’t work out. And some people say it works for them.

But recent studies and data are now questioning gabapentin’s role as a benign catch-all. They’re finding that, when used along with other drugs, gabapentin does have the potential to be misused, and is linked to an increased risk of death when combined with opioids—a connection that’s particularly alarming since it’s so often prescribed for pain. A handful of lawsuits allege that its use is associated with suicide, a worrying correlation for a medication given to people with pre-existing mental health disorders.

The vast majority of gabapentin prescriptions are for off-label uses, or uses not approved by the FDA—an estimated 95 percent, according to a study of nationwide data. One survey found that gabapentin has the highest proportion of off-label prescriptions out of 160 commonly used drugs.

These incredibly large numbers just don’t make sense, said Chris Goodman, an assistant professor of clinical internal medicine at the University of South Carolina School of Medicine, who has published two papers examining gabapentin use in the U.S. There are no well-designed, placebo-controlled clinical trials for several of its off-label applications, said Joe Ross, a primary care physician at Yale University and a researcher on pharmaceutical policy. Some off-label uses may have one or two studies, but the results are either modest or inconsistent—overall, only about 20 percent of gabapentin’s off-label uses have data supporting them, Ross said.

Goodman thinks there is reason to be wary of doctors writing so many off-label gabapentin prescriptions: When it was first patented, the company that produced it spent millions of dollars on a deceptive marketing campaign specifically to promote gabapentin’s off-label potential. He thinks it’s worth asking if the legacy of that marketing campaign is in some way responsible for the sheer amount of off-label use that still takes place today.

Goodman thinks there is reason to be wary of doctors writing so many off-label gabapentin prescriptions: When it was first patented, the company that produced it spent millions of dollars on a deceptive marketing campaign specifically to promote gabapentin’s off-label potential. He thinks it’s worth asking if the legacy of that marketing campaign is in some way responsible for the sheer amount of off-label use that still takes place today.

Parke-Davis hired medical education companies to write review papers, original articles, and letters to the editor in medical journals about gabapentin for “$13,375 to $18,000 per article,” plus a $1,000 honorarium for the author. The majority of these articles had “favorable” conclusions about gabapentin, and in most instances the payments were not disclosed.

Parke-Davis executives spent hundreds of thousands of dollars targeting medical residents to—as explained in one document—“influence physicians from the bottom up” and “to solidify Parke-Davis’ role in the resident’s mind as he/she evolves into a practicing physician.”
The company invested in “education” as a strategy, as when they organized teleconferences that connected paid doctor “moderators” with other doctors. These events were described publicly as purely educational, but one internal memo from 1995 said that “the key goal of the teleconferences was to increase new Neurontin prescriptions by convincing non-prescribers to begin prescribing and current prescribers to increase their new prescription behavior.”

Some of the company-funded research was intended to get FDA approval for treating more conditions, but Parke-Davis said internally that the goal of other studies was to “disseminate the information as widely as possible through the world’s medical literature generating excitement in the market and stimulating off-label prescribing despite the lack of FDA approval.”
In the New England Journal of Medicine (NEJM) in 2009, researchers took a closer look at the gabapentin studies that were funded by Parke-Davis. One author, epidemiologist Kay Dickersin, said she found a number of reporting biases that affect the results of the research. One placebo-controlled study was delayed because it found that there was no effect on the primary outcome, which was neuropathic pain. Documents showed that the company held the study because “[Parke–Davis employees] should take care not to publish anything that damages neurontin’s marketing success.” Trials with findings that were not statistically significant were either not published in full, or were published only after their primary outcomes were changed, which skewed the results to be significant. Other studies were manipulated to minimize or hide negative findings about the drug.

In April 1996, a biologist named David Franklin began working at Parke-Davis. Franklin knew that according to FDA rules, he was not allowed to promote off-label uses of drugs, and yet, the NEJM recounted that an executive allegedly told him:

“I want you out there every day selling Neurontin. … We all know Neurontin’s not growing for adjunctive therapy [when it gets combined with another medication], besides that’s not where the money is. Pain management, now that’s money…That’s where we need to be, holding their hand and whispering in their ear, Neurontin for pain, Neurontin [alone], Neurontin for bipolar, Neurontin for everything. I don’t want to see a single patient coming off Neurontin before they’ve been up to at least 4800 mg/day. I don’t want to hear that safety crap either, have you tried Neurontin, every one of you should take one just to see there is nothing, it’s a great drug.”

Franklin quit three months later and became a whistleblower, filing a lawsuit that ended with Parke-Davis’ parent company pleading guilty in 2004 to resolve criminal charges and civil liabilities and paying $420 million in fines. Despite the lawsuits and guilty pleas, more than ten years later, Michael Steinman, a professor of medicine at UCSF, said it’s hard to know if gabapentin would be so widely used today if it weren’t for all the money poured into the off-label marketing campaigns.

“It certainly didn’t hurt,” he said. “I think the legacy of that has been that off-label prescription of gabapentin has persisted. Gabapetin has found a kind of niche to treat all sorts of things that doctors don’t know what to do with.”

“It certainly didn’t hurt,” he said. “I think the legacy of that has been that off-label prescription of gabapentin has persisted. Gabapetin has found a kind of niche to treat all sorts of things that doctors don’t know what to do with.”

A Cochrane review, a type of highly respected analysis that combines results from multiple studies, found that while gabapentin does seem to provide pain relief for its on-label uses, the support for others was limited. Reviews on other off-label applications, like for migraine, fibromyalgia, mental illness, and substance dependence have “found modest to no effect on relevant clinical outcomes,” according to a 2018 paper in Substance Abuse: Research and Treatment.

 

 

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