'Off-Label' Drug Use Is Common

Report ID's 14 Drugs Prescribed for Conditions for Which They Are Not Approved by the FDA

Medically Reviewed by Louise Chang, MD on November 24, 2008
From the WebMD Archives

Nov. 24, 2008 -- It is common for doctors to prescribe drugs for conditions they aren't specifically approved for, but in many cases there is not enough evidence to justify the practice, a new report concludes.

Researchers from Stanford University and the University of Illinois-Chicago identified 14 drugs widely prescribed for so-called off-label uses that they say are most in need of additional study.

Six antidepressants and three antipsychotic medications made the list, and the most common off-label use for these drugs was the maintenance treatment of bipolar disorder.

The antipsychotic drug Seroquel (quetiapine) topped the list. The drug was approved for the treatment of schizophrenia and mania-associated biopolar disorder at the time of the analysis, but the researchers found that three out of four Seroquel prescriptions were written for other conditions.

In May of this year, the FDA also approved the drug for the maintenance treatment of bipolar disorder in patients also taking lithium or divalproex.

The drug's high cost -- averaging about $200 per prescription -- and concerns about an increased risk of death in dementia patients contributed to its No. 1 ranking as a medication that needs further study.

Seroquel is often prescribed off-label for the treatment of depression and anxiety, and researcher Randall S. Stafford, MD, PhD, of the Stanford Prevention Research Center tells WebMD that it is often prescribed as maintenance therapy to bipolar patients who are not taking lithium or divalproex.

The researchers concluded that the research on antipsychotics for these uses is limited.

Drugmaker Responds

In response to the report, Abigail Baron, a spokeswoman for Seroquel-manufacturer AstraZeneca tells WebMD that the company does not promote the drug for off-label uses.

It is illegal for pharmaceutical companies to actively market their drugs for uses that they are not specifically approved for, but sales reps are allowed to tell doctors about published research that supports these off-label uses.

"Seroquel has helped millions of people suffering from bipolar disorder and schizophrenia and helped many lead more productive lives," Baron notes.

"It is AstraZeneca's policy to promote its medicines in accordance with FDA regulation and to train its sales force to follow this policy. We have extensive policies in place to provide direction about the appropriate promotion of our product based upon the FDA-approved indications and consistent with FDA regulations."

Drugs That Need More Study

Stafford agrees that off-label prescribing is an important feature of clinical practice.

But he says many of the most common uses for the drugs identified in his report have not been adequately studied.

There are situations where it makes sense, especially when there are few other treatment options, he says. "But we are talking about millions of prescriptions a year, and the size and rigor of the studies that have been done may not justify this."

The blood thinner Coumadin (known generically as warfarin) was included in the report. The drug is widely prescribed for the treatment of hypertensive heart disease and coronary heart disease, but it is not approved for these uses.

Two other antipsychotics -- Risperidal (risperidone) and Zyprexa (olanzapine) -- also made the list. Both are approved for the treatment of schizophrenia, but are often prescribed off-label for the treatment of depression.

The six antidepressants identified in the report included:

  • Lexapro (escitalopram)
  • Zoloft (sertraline)
  • Effexor (venlafaxine)
  • Cymbalta (duloxetine)
  • Wellbutrin (Bupropion)
  • Desyrel (trazodone)

Once again, the treatment of bipolar disorder was the most common off-label use for most of the antidepressants identified in the report.

The four other drugs identified in the report were:

  • The asthma drug Singulair (montelukast), commonly prescribed off-label for chronic obstructive pulmonary disorder (COPD).
  • The arthritis drug Celebrex (celecoxib), with fibromatosis being the most common off-label use.
  • The ACE inhibitor Prinivil or Zestril (lisinopril), most commonly used off label for coronary artery disease.
  • The drug Procrit or Epogen (epoetin alfa), approved for anemia in patients with kidney failure, but widely used in patients with other chronic diseases.

"We are not trying to say that these uses are necessarily bad," University of Illinois-Chicago economist and study researcher Surrey M. Walton, PhD, tells WebMD. "It is just that there hasn't been enough evidence established for it."

Show Sources


Walton, S.M. Pharmacotherapy, 2008; vol 28: pp1443-1452.

Randall S. Stafford, MD, PhD, associate professor of medicine, Sanford Prevention Research Center, Stanford University, Stanford, Calif.

"FDA Alert: Increased Mortality in Patients with Dementia-Related Psychosis," September 2006.

Abigail Baron, spokeswoman, AstraZeneca.

Surrey Walton, PhD, assistant professor pharmacy administration, University of Illinois-Chicago.

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