Off-Label Drug Use Extremely Common

Numerous studies have quantified the widespread practice of prescribing drugs off-label, but many patients are unaware that it is allowed, according to a new analysis.

Off-label drug use (OLDU) is extremely common, yet many patients appear to be unaware that they are engaging in the practice, according to an analysis that will appear in the October 2012 issue of Mayo Clinic Proceedings.

OLDU involves the prescription of a medication for an indication, for a patient population, or at a dosage level or in a dosage form that has not been approved by the FDA. (The FDA approves medications for marketing based on evidence that they are safe and effective, but once a given medication has been approved, the agency does not control how it is prescribed or used.) Situations that may lead to OLDU include when other medications in the same class have been approved for a given condition or when a medication is approved for a similar condition. If a medication has been approved to treat 1 condition, it may not make financial sense for its manufacturer to get it approved for another indication.

A number of recent studies have documented how widespread OLDU is. A 2006 study found that 21% of prescriptions of a group of commonly used medications were for off-label use. Another study found that 78.9% of children discharged from pediatric hospitals were taking at least 1 off-label medication and that the estimated rate of OLDU in a pediatric emergency department was 26.2%.

OLDU occurs in all specialty areas, but is particularly common among children, pregnant women, and psychiatric patients because these groups are less likely to be included in clinical trials. For example, morphine has not been approved by the FDA for treatment of pain in children, but is used extensively for this purpose among hospitalized children. Also commonly used off-label in children are inhaled bronchodilators, antimicrobials, anticonvulsants, and proton pump inhibitors.

There is a good deal of crossover among psychiatric conditions, prompting providers to use psychiatric drugs approved for one condition to treat other psychiatric conditions as well. For example, a study estimated that the total cost of off-label use of antipsychotics reached $6 billion in 2008. In addition, selective serotonin reuptake inhibitors are used off-label for conditions such as borderline personality disorder, stuttering, pathological gambling, and alcoholism.

In a number of cases, OLDU has become widely accepted or even the standard of care. Examples of this include the prescription of tricyclic antidepressants to treat neuropathic pain and aspirin for prevention of coronary disease in diabetes patients. However, in many instances, OLDU lacks sound backing. One study found that 73% of medications prescribed for off-label use had poor or no scientific support. In critical-care patients, this was the case 48.3% of the time.

There is no requirement for physicians to get informed consent from patients when prescribing medications off-label, which is justified on the grounds that doing so could unduly alarm patients and take up valuable time that would be better directed toward more pressing elements of care. However, a 2006 nationwide poll found that half of respondents believed that OLDU was not allowed and that two-thirds of respondents thought that OLDU should be banned except for clinical trials. Of course, the authors note, many of these respondents are likely to have unwittingly benefited from OLDU.

Drug manufacturers are generally prohibited from promoting off-label uses of medications that have been approved for other indications. However, they are allowed to respond to unsolicited questions from health-care providers regarding off-label uses (via medical affairs staff, not marketing staff) and to distribute peer-reviewed publications regarding off-label use, provided that they make their connection to the material clear. The FDA has established a mechanism by which patients and health care professionals can report illicit OLDU promotion by drug manufacturers—and such promotion has led to several high-profile penalties to manufacturers in recent years.