When the Food and Drug Administration approves a drug, the agency spells out who the drug is for, how to use it, and what it’s supposed to treat. But your doctor isn’t legally bound to follow those rules, and about 20 percent of U.S. prescriptions are off-label—written by doctors for a non-FDA-approved use. That means he might, for example, prescribe a blood pressure pill to calm your stage fright or an antidepressant to quell hot flashes.

In some cases, off-label prescribing makes sense, says Gordon Schiff, M.D., associate director at the Center for Patient Safety Research and Practice at Brigham and Women’s Hospital in Boston. But, he cautions, unapproved uses have often not been well-studied and may not bring hoped-for benefits or may increase the risk of adverse effects.

For FDA approval, drugmakers must show that a drug works and is safe for its intended use. Unapproved uses don’t undergo that scrutiny. For example, one study of more than 46,000 people found that about 80 percent of off-label prescribing was for a use not backed by strong scientific evidence. That increased the risk of a negative side effect by 54 percent (compared with those taking the same drug for an approved use or a more thoroughly studied use).

Is Your Doctor in the Dark?

Doctors aren’t required to tell you if they are prescribing a drug off-label. In fact, they may not always know.

A survey of 457 primary care physicians and psychiatrists found that many mistakenly thought common unapproved uses for certain drugs were FDA-approved. Almost 20 percent of doctors who said they prescribed the antipsychotic quetiapine (Seroquel and generic) for agitation, aggression, and hallucinations in seniors with dementia didn’t realize the drug wasn’t approved for those purposes. More concerning, the drug carries a black box warning (the strongest type) that it increases the risk of death in those patients.

Certain drug companies might illegally promote off-label uses to healthcare practitioners. In recent years, firms have racked up billions of dollars in fines “as a cost of doing business,” Schiff says. In 2013, Johnson & Johnson agreed to pay more than $2.2 billion to resolve charges of, among other things, promoting off-label use of the antipsychotic risperidone (Risperdal). More recently, Endo Pharmaceuticals agreed to pay almost $200 million for promoting Lidoderm—a patch approved for shingles-related nerve pain—for many other types of pain.

We may soon see more off-label marketing. Last year, Amarin Pharma began promoting off-label use of a prescription fish-oil pill after a federal court ruled that such marketing was protected by the right to free speech. The FDA has also proposed regulations that would give drug and device makers more leeway in distributing information about off-label uses for their products.

When Off-Label Prescribing Has Benefits

Off-label prescribing can sometimes be useful for treating people outside a drug’s approved group—such as those who are older. Also, doctors may want to take advantage of an emerging use of a drug, notably for patients with limited options. Off-label use of cancer drugs is quite common, for example, because some work against several types of tumors.

And there’s good evidence behind certain off-label uses. Take the anti­seizure drug topiramate. It has been recommended in U.S. and international guidelines for treating alcohol dependence. The antidepressant amitriptyline is recognized as a first-line therapy for fibromyalgia pain and costs less than approved treatments.

Questions to Ask

Before you take a new drug, ask your doctor or pharmacist whether it’s for an approved use. (Or go to dailymed.nlm.nih.gov, search by drug, then click Indications & Usage.) If it’s not, ask whether the use is supported by well-designed trials and why he thinks it’s better than approved drugs for you. And call your insurance company. Insurers might not cover off-label use or may require proof that conventional treatments failed and that the off-label drug will work for you.

Drugs commonly prescribed off-label without good evidence

Generic Name

Brand Name

Condition(s) Commonly Prescribed Off-Label For:

Quinine sulfateQualaquinNighttime leg pain
ClonazepamKlonopin

Restless legs syndrome, Insomnia

GabapentinNeurontinDiabetic peripheral neuropathy
TrazodoneOleptro

Anxiety, Insomnia

QuetiapineSeroquel

Dementia, Obsessive-compulsive disorder

Editor's Note: These materials were made possible by a grant from the state Attorney General Consumer and Prescriber Education Grant Program, which is funded by the multi-state settlement of consumer fraud claims regarding the marketing of the prescription drug Neurontin (gabapentin).