Off Label, Off Base?

By Sandra G. Boodman
Washington Post Staff Writer
Tuesday, May 23, 2006

Every day in medical offices around the country, physicians hand patients prescriptions for drugs to treat conditions for which the medicines haven't been approved. Once a drug is approved by the Food and Drug Administration (FDA), a doctor can, with rare exceptions, legally prescribe it "off label": for use as he or she sees fit.

That's a primary reason people with depression or attention-deficit disorder are prescribed drugs approved to treat seizures, acne patients are given prescriptions for antibiotics, and insomniacs are advised to take a schizophrenia drug. And it's why tens of millions of post-menopausal women for years were told to take estrogen, a drug approved to treat osteoporosis, as a way of staving off heart disease, improving their mood and memory, and smoothing wrinkles.

Off-label use of drugs may be axiomatic in medicine, but a new study published in the Archives of Internal Medicine finds that the practice is frequently grounded more in anecdote than in hard science.

Using data from a national survey of 3,500 office-based physicians, researchers found that 21 percent of the 725 million prescriptions written in 2001 were for off-label uses. Seventy-three percent of these prescriptions lacked strong scientific justification, such as a clinical trial, and were based on observational studies, case reports or no discernable evidence. And without solid evidence of safety and effectiveness, the researchers maintain, consumers run the risk of taking ineffective, expensive and potentially dangerous drugs.

Estrogen is one such example. Only after doctors had prescribed it for decades to prevent a panoply of problems did a large clinical trial in 2002 find that the hormone actually increased the risk of heart disease, stroke, breast cancer, incontinence and dementia.

The new study, funded by the federal Agency for Healthcare Research and Quality, compared patients' diagnoses with labeling information from the 100 most commonly prescribed drugs, as well as 60 randomly selected medications. Researchers then assessed the amount of scientific support for each case of off-label use.

Some prescriptions were logical extensions of the approved labeling, such as giving an asthma drug to treat another lung ailment. Others were less clear, such as using a seizure drug to quell anxiety.

"There is enormous variation in the reason drugs are used off-label, from extremely good evidence to experimentation," said Randall Stafford, one of the study's co-authors. Stafford, an assistant professor of medicine at Stanford University, said he was surprised by how many prescriptions were written without solid scientific justification. In psychiatry, for example, researchers found that 96 percent of off-label prescriptions lacked strong scientific support.

David Schopick, who practices in Portsmouth, N.H., said he thinks some of his fellow child psychiatrists "draw the line where we think our colleagues draw the line" between innovation, which is ethical, and experimentation, which is not. Enthusiasm for off-label prescribing has waned somewhat in psychiatry, he added, because of reports that antidepressants may trigger suicidal behavior in teenagers. "So much of what we prescribe has not been shown to be effective" in children, but has been approved for adults, he added.

In addition to psychiatric medications, drugs to treat heart disease, asthma, allergies and seizures are commonly prescribed for unapproved uses, the study found. Drugs used to lower cholesterol and control diabetes were least likely to be prescribed for other conditions, researchers found.

Reasons for the burgeoning practice vary, Stafford and other experts say. Some doctors may be swayed by small, promising studies funded by manufacturers tempted to increase a drug's sales without going through the expensive, time-consuming process of expanding its approved uses. (FDA regulations prohibit companies from marketing a drug to treat a condition for which it hasn't been specifically approved.)

In other cases, influential practitioners known as "thought leaders" in their specialty may endorse the use of a drug, their views then spread by word of mouth, especially at conferences.

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