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
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.
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
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.
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.
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
Working the system
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.)
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.
AMA's Nielsen acknowledges that she and other physicians remain concerned
about the increasing influence drug makers have over doctors'
Mariann Caprino, a Pfizer spokeswoman, says the
illegal activity highlighted in the Neurontin case happened before the
company acquired Warner-Lambert in 2000.
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.
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.
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.
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."