'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

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

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

Six antidepressants and threeantipsychotic medications made the list, and the most common off-label use forthese drugs was the maintenance treatment of bipolar disorder.

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

In May of this year, the FDA also approved the drug for the maintenancetreatment of bipolar disorder in patients also taking lithium ordivalproex.

The drug's high cost -- averaging about $200 per prescription -- andconcerns about an increased risk of death in dementia patients contributedto 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 RandallS. Stafford, MD, PhD, of the Stanford Prevention Research Center tells WebMDthat it is often prescribed as maintenance therapy to bipolar patients who arenot taking lithium or divalproex.

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

Drugmaker Responds

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

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

"Seroquel has helped millions of people suffering from bipolar disorderand schizophrenia and helped many lead more productive lives," Baronnotes.

"It is AstraZeneca's policy to promote its medicines in accordance withFDA regulation and to train its sales force to follow this policy. We haveextensive policies in place to provide direction about the appropriatepromotion of our product based upon the FDA-approved indications and consistentwith FDA regulations."

Drugs That Need More Study

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

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

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

The blood thinner Coumadin (known generically as warfarin) was included in thereport. The drug is widely prescribed for the treatment of hypertensive heart disease and coronary heartdisease, 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 ofschizophrenia, but are often prescribed off-label for the treatment ofdepression.

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-labeluse 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 pulmonarydisorder (COPD).
  • The arthritis drug Celebrex(celecoxib), with fibromatosis being the most common off-label use.
  • The ACE inhibitor Prinivil or Zestril (lisinopril), most commonly usedoff label for coronary artery disease.
  • The drug Procrit or Epogen (epoetin alfa), approved for anemia in patientswith kidney failure, but widely used in patients with other chronicdiseases.

"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 evidenceestablished 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.

© 2008 WebMD, LLC. All rights reserved. View privacy policy and trust info