After two months of sleepless nights, anxiety and constantly feeling like she was "swimming in a thick fog all day long," Caryl Westwood was fed up. She suspected her pain medication, Neurontin, which her doctor had recently prescribed for her lower back pain.
What Westwood didn't know -- and she says her doctor didn't tell her -- was that Neurontin wasn't a pain medication at all. Instead, it was a powerful epilepsy drug that doctors across the country were increasingly prescribing for many conditions for which the drug had not been approved: attention deficit disorder, migraines, drug and alcohol addiction, and pain. Surprisingly, there was little clear proof Neurontin worked for any of these conditions.
Although doctors are allowed to prescribe an FDA-approved drug for any reason they see fit, companies are barred from marketing or promoting drugs for any use beyond what's listed on its label. Last month, Pfizer Inc. agreed to plead guilty and pay a $430-million fine to settle federal criminal charges that the pharmaceutical giant promoted Neurontin for uses for which it had no scientific support.
According to the government's complaint, the promotion amounted to an "illegal and fraudulent promotion scheme" that put patients "at risk." It is estimated that 90% of Neurontin's $2.7 billion in sales last year were for off-label uses.
"I'm angry," says Westwood, a 52-year-old food service worker from Santa Fe, N.M. "How could a doctor not tell their patient about this? How can the government let this happen?"
Off-label prescription drugs are immensely common -- accounting for up to 40% of all prescriptions written each year. In the vast majority of cases, the practice is safe. Moreover, off-label use has spawned many medical innovations that doctors might otherwise not have discovered.
It's how medical science first learned that aspirin could reduce the risk of heart disease; that antibiotics were the best way to treat ulcers; and that an angina drug produced an unexpected side effect in men, which would later lead to the development of the blockbuster drug Viagra.
Moreover, stories about the importance of off-label usage to treat life-threatening conditions such as AIDS and cancer are plentiful. Most front-line drugs used to treat terminal illnesses are approved for one purpose, but then quickly prescribed as a second or third option for patients with other illnesses who don't respond to traditional treatments. A 1997 survey by the American Cancer Society found that 60% of cancer doctors used drugs for unapproved reasons.
The American Medical Assn. says it strongly supports doctors' rights to prescribe FDA-approved drugs for any reasons that physicians believe are helpful. Such uses do not, as some critics charge, amount to turning patients into human guinea pigs, says Dr. Nancy Nielsen, a Buffalo, N.Y., internist and speaker of the AMA's House of Delegates. Doctors, she says, "are making decisions based on the best science and what's in the patient's best interest."
Still, the Neurontin case and other ongoing federal investigations into drug makers' promotions of off-label uses, indicate that the government is growing increasingly worried about the issue. The concern is that some drug companies are finding ways to abuse the system and promote their products for unapproved use even when they have little good science to back up their claims. Both Schering-Plough Corp. and Wyeth are being investigated by the federal government for their off-label prescription practices.
In some cases, taking a drug off- label may be a waste of money. As highly effective as some new drugs can be, older and cheaper drugs often are sometimes just as effective. In other cases, there's a risk to taking medications for conditions for which the FDA never evaluated the drug. It wasn't long ago, after all, that doctors were regularly prescribing fen-phen, a combination of two FDA-approved drugs -- fenfluramine and phentermine -- as an unapproved weight-loss treatment that was later suspected of causing heart valve damage in up to 30% of users.
Dr. Raymond Woosley, vice president of the Arizona Health Sciences Center at the University of Arizona in Tucson, says that most patients taking off-label drugs are getting the best treatment.
Even so, Woosley cautions that patients should be careful, especially when taking a relatively new drug that is being prescribed for several off-label uses, or when a drug is being used off-label for medical conditions not well understood by doctors and for which there are no "standard" treatments.
One example: drugs used to treat neurological conditions, such as depression, attention deficit disorder or anxiety. The brain "is still a vastly confusing area," he says, "and that's something drug companies can exploit."
Working the system
One important way that companies can circumvent regulations is by capitalizing on the different rules and accepted practices involving scientific research. In some cases, well-respected research articles demonstrating another use for an FDA-approved drug appear in major medical journals years before the agency catches up and endorses it.
In those cases, it's perfectly acceptable for drug companies to talk about those newly discovered benefits. The problem is, not all research is created equal. In some cases, drug companies conduct their own research and then hire ghostwriters to put their name on a paper before it's submitted for publication. (That relationship isn't always disclosed.)
As recently as the mid-'90s, the FDA tried to block companies from sending questionable research material directly to doctors. The agency was stymied by successful industry lawsuits claiming the practice was protected under free speech. The FDA still insists that drug companies can distribute research only after a physician has requested it.
There are ways around that too. Some doctors say that drug representatives start a conversation by saying they can't talk about off-label uses. But then, they will say that other doctors have used the drug for different reasons and they'd be happy to send along information about some ideas.
The AMA's Nielsen acknowledges that she and other physicians remain concerned about the increasing influence drug makers have over doctors' decision-making.
Mariann Caprino, a Pfizer spokeswoman, says the illegal activity highlighted in the Neurontin case happened before the company acquired Warner-Lambert in 2000.
Officials of Schering-Plough acknowledged in an interview that the company is under investigation by the U.S. Justice Department for off-label marketing of a cancer medication, while Wyeth said the federal Office of Personnel Management, the agency that oversees benefits for federal employees, has subpoenaed company records involving Wyeth's promotion of an antidepressant drug, Effexor.
Curbs in question
It's unclear just how effective the government's actions will be in curbing off-label marketing. Two years ago, the pharmaceutical industry instituted voluntary guidelines to ban most gifts and payments to doctors, which were aimed at slowing aggressive marketing tactics around both on-label and off-label promotions.
But some companies continue to underwrite seminars for doctors where off-label uses are discussed while others pay doctors to sit in the room with patients and discuss treatment advice, a financial agreement some characterize as quid pro quo payments.
Doctors are not required to tell patients they are writing off-label prescriptions, but many will discuss it if patients ask. Patients can also seek information about a drug's authorized uses on the FDA's website (www.fda.gov).
As part of its settlement agreement, Pfizer is required to spend a portion of its fine -- $38 million -- on a public-awareness campaign for doctors and patients.
After hearing about Pfizer's fine last month, Westwood says she decided to file a complaint against her doctor with the state medical board for not informing her Neurontin was not approved by the FDA as a pain medication and certain other uses. She realizes that the board is unlikely to act, but she remains resolute.
"I don't want anyone to have to go through this," she says. "It's not right."