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David C. Radley, MPH; Stan N. Finkelstein, MD; Randall S. Stafford, MD, PhD

Arch Intern Med. 2006;166:1021-1026.

Background  Unlike medicines prescribed for Food and Drug Administration–approved indications, off-label uses may lack rigorous scientific scrutiny. Despite concerns about patient safety and costs to the health care system, little is known about the frequency of off-label drug use or the degree of scientific evidence supporting this practice.

Methods  We used nationally representative data from the 2001 IMS Health National Disease and Therapeutic Index (NDTI) to define prescribing patterns by diagnosis for 160 commonly prescribed drugs. Each reported drug-diagnosis combination was identified as Food and Drug Administration–approved, off-label with strong scientific support, or off-label with limited or no scientific support. Outcome measures included (1) the proportion of uses that were off-label and (2) the proportion of off-label uses supported by strong scientific evidence. Multivariate analyses were used to identify drug-specific characteristics predictive of increased off-label use.

Results  In 2001, there were an estimated 150 million (95% confidence interval, 127-173 million) off-label mentions (21% of overall use) among the sampled medications. Off-label use was most common among cardiac medications (46%, excluding antihyperlipidemic and antihypertensive agents) and anticonvulsants (46%), whereas gabapentin (83%) and amitriptyline hydrochloride (81%) had the greatest proportion of off-label use among specific medications. Most off-label drug mentions (73%; 95% confidence interval, 61%-84%) had little or no scientific support. Although several functional classes were associated with increased off-label use (P<.05), few other drug characteristics predicted off-label prescription.

Conclusions  Off-label medication use is common in outpatient care, and most occurs without scientific support. Efforts should be made to scrutinize underevaluated off-label prescribing that compromises patient safety or represents wasteful medication use.

Author Affiliations: Center for Evaluative Clinical Sciences, Dartmouth Medical School, Hanover, NH (Mr Radley); Program on the Pharmaceutical Industry, Sloan School of Management, Massachusetts Institute of Technology, Cambridge (Dr Finkelstein); and Program on Prevention Outcomes and Practices, Stanford Prevention Research Center, Stanford, Calif (Dr Stafford). Dr Finkelstein is now additionally with Harvard Medical School, Boston, Mass.

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