Why off-label isn’t off base

Is off-label use malpractice?

Off-label use is not only legal, it’s often wise medical practice. Many drug uses that now have FDA approval were off-label just a few years ago. Examples include using selective serotonin reuptake inhibitors (SSRIs) to treat panic disorder and obsessive-compulsive disorder and valproate for bipolar mania. Though fluoxetine is the only FDA-approved drug for treating depression in adolescents, other SSRIs may have a favorable risk-benefit profile.⁶

Numerous studies have shown that off-label prescribing is common in psychiatry⁷ and other specialties.^8,9 Because the practice is so common, the mere fact that a drug is not FDA-approved for a particular use does not imply that the drug was prescribed negligently.

Are patients human guinea pigs?

Some commentators have suggested that off-label prescribing amounts to human experimentation.¹⁰ Without FDA approval, they say physicians lack “hard evidence” that a product is safe and effective, so off-label prescribing is a small-scale clinical trial based on the doctor’s educated guesses. If this reasoning is correct, off-label prescribing would require the same human subject protections used in research, including institution review board approval and special consent forms.

Although this argument sounds plausible, off-label prescribing is not experimentation or research (Box).^4,11-19 Researchers investigate hypotheses to obtain generalizable knowledge, whereas medical therapy aims to benefit individual patients. This experimentation/therapy distinction is not perfect because successful off-label treatment of 1 patient might imply beneficial effects for others.¹⁰ When courts have looked at this matter, though, they have found that “off-label use…by a physician seeking an optimal treatment for his or her patient is not necessarily…research or an investigational or experimental treatment when the use is customarily followed by physicians.”⁴

Courts also have said that off-label use does not require special informed consent. Just because a drug is prescribed off-label doesn’t mean it’s risky. FDA approval “is not a material risk inherently involved in a proposed therapy which a physician should have disclosed to a patient prior to the therapy.”²⁰ In other words, a physician is not required to discuss FDA regulatory status—such as off-label uses of a medication—to comply with standards of informed consent. FDA regulatory status has nothing to do with the risks or benefits of a medication and it does not provide information about treatment alternatives.²¹

What should you do?

Keep abreast of news and scientific evidence concerning drug uses, effects, interactions, and adverse effects, especially when prescribing for uses that are different from the manufacturer’s intended purposes (such as hormone therapy for sex offenders).²²

Collect articles on off-label uses, but keep them separate from your patients’ files. Good attorneys are highly skilled at using documents to score legal points, and opposing counsel will prepare questions to focus on the articles’ faults or limitations in isolation.

Know why an article applies to your patient. If you are sued for malpractice, you can use an article to support your treatment choice by explaining how this information contributed to your decision-making.

Tell your patient that the proposed treatment is an off-label use when you obtain consent, even though case law says you don’t have to do this. Telling your patient helps him understand your reasoning and prevents surprises that may give offense. For example, if you prescribe a second-generation antipsychotic for a nonpsychotic patient, you wouldn’t want your patient to think you believe he has schizophrenia when he reads the information his pharmacy attaches to his prescription.

Engage in ongoing informed consent. Uncertainty is part of medical practice and is heightened when doctors prescribe off-label. Ongoing discussions help patients understand, accept, and share that uncertainty.

Document informed consent. This will show—if it becomes necessary—that you and your patient made collaborative, conscientious decisions about treatment.²³

Related resources

• Zito JM, Derivan AT, Kratochvil CJ, et al. Off-label psychopharmacologic prescribing for children: history supports close clinical monitoring. Child Adolesc Psychiatry Ment Health. 2008;2:24. www.capmh.com/content/pdf/1753-2000-2-24.pdf.
• Spiesel S. Prozac on the playground. October 15, 2008. Slate. www.slate.com/id/2202338.

Drug brand names

• Fenfluramine and phentermine • Fen-phen
• Fluoxetine • Prozac
• Sildenafil • Viagra
• Valproate • Depakote