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Off-Label Drugs: What They Are and What It Means for You

As Ida Kalde’s Alzheimer’s disease progressed, she became increasingly confused, combative and delusional. She accused her son and daughter-in-law, Pete and Evelyn Ruut, whose Kingston, N.Y., home she lived in, of hiding the baby she thought she had given birth to. “We were nearly at the end of our rope,” Evelyn Ruut says.

To help quiet Kalde, her doctor prescribed the antipsychotic medication Risperdal. “She was noticeably calmer, more normal acting and appearing than she had been in a long time,” Evelyn says. Kalde was able to live with her family for three more years.

Risperdal was approved by the U.S. Food and Drug Administration for treating schizophrenia but not Alzheimer’s. That meant Kalde was taking the drug for “off-label” use, a controversial practice that can benefit patients in some instances but endanger them in others.

While companies by law can market their drugs only for the diseases approved by the FDA, doctors can prescribe them for other conditions—a colon cancer drug, for example, to treat breast cancer—if other therapies are less effective or nonexistent.

Millions of American take drugs off-label, particularly for cancer, AIDS, mental health disorders and chronic pain. A 2001 survey published in the Archives of Internal Medicine in 2006 found that one in five of the 500 most commonly prescribed drugs was for off-label use.

Proponents say new uses for old medications are often discovered serendipitously, turning out to be safe, beneficial and even life-saving for patients with hard-to-treat or potentially fatal illnesses. One example: Thalidomide, a drug used in the 1950s to treat morning sickness in pregnant women—and later found to cause severe birth defects—reappeared four decades later as an FDA-approved treatment for leprosy sores and other serious skin problems.

“Much off-label use is not warranted, but some of it may be appropriate,” says Jerry Avorn, M.D., professor of medicine at Harvard Medical School and author of Powerful Medicines (Random House, 2004).

Critics are concerned that some drugs are prescribed off-label without conclusive testing for effectiveness and safety. Without clinical trials, physicians are essentially operating in an “evidence-free zone,” says Adriane Fugh-Berman, M.D., an associate professor at the Georgetown University School of Medicine and lead investigator of PharmedOut, a project that educates doctors about the influence of pharmaceutical companies on prescribing patterns.

“So many drugs are being used by so many patients without objective research [or] evidence,” says Diana Zuckerman, president of the National Research Center for Women & Families in Washington. “Based on their experience with relatively small numbers of patients, doctors may believe that the drugs are effective, but that is not conclusive evidence—and certainly not evidence that those medications are the best choices available.”

But getting that evidence isn’t easy. “Because our nation relies on the pharmaceutical industry to do nearly all the evaluation of drugs for efficacy and risk,” Avorn says, “we are at the mercy of what the industry chooses to study or not.”

Still, the industry has taken some hits for promoting drugs for off-label purposes. In 2004 drugmaker Warner-Lambert was slapped with a $430 million fine for pushing Neurontin, approved for epileptic seizures, as off-label treatment for pain, mood disorders, attention deficit disorder and migraines. In 2005 Eli Lilly was fined $36 million for illegally promoting the osteoporosis drug Evista to lower the risk of breast cancer, despite prior FDA rejection of Lilly’s proposed labeling for this use.

Pharmaceutical companies also got some bad news about using antipsychotic medications to treat dementia patients like Ida Kalde. A $16.9 million federally funded study—the Clinical Antipsychotic Trials of Intervention Effectiveness, or CATIE, study—recently examined the practice over five years. It found that any benefit of Zyprexa, Seroquel and Risperdal for Alzheimer’s patients was offset by side effects, including sedation, weight gain and confusion.

The CATIE study is a rare exception, says Harvard’s Avorn: “The voice of evidence-based medicine is much softer than the voice of industry.”

Now the FDA is proposing new guidelines that would give the industry an even louder voice by allowing drug sales reps to give doctors peer-reviewed medical journal articles about off-label uses for drugs and medical devices. The FDA says distributing “truthful and non-misleading medical journal articles” can advance public health.

But others see the proposed change as advancing the drug industry’s health uses. “The new guidelines would definitely increase overt off-label promotion,” Fugh-Berman says, “and we have enough problems with covert promotion.”