Let's Not Criticize Off-Label Prescribing

Robert S. Emmons, MD, and Renée S. Kohanski, MD

March 26, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

The public health crisis sparked by COVID-19 has engendered much debate in the realm where politics, journalism, law, and medicine meet.

Doctors have used the media to name other doctors as sources of harmful misinformation, in some cases going so far as to invoke medical practice board oversight as a potential intervention when doctors make public statements deemed too far out of bounds scientifically. Over the past year, some physicians have been harshly criticized for speaking about off-label prescribing, a widely accepted part of everyday medical practice.

The science and ethics of off-label prescribing have not changed; what has changed is the quality of dialogue around it. As psychiatrists, it does not fall within our scope of practice to offer definitive public opinions on the treatment of COVID-19, nor is that our purpose here. However, we can speak to a process that damages patients and doctors alike by undermining trust. All of this heat around bad medical information, in our opinion, amounts to using the methods of other fields to evaluate science and clinical practice. A remedy, then, to improve the quality of public medical intelligence would be to clarify the rules of scientific debate and to once again clearly state that off-label prescribing is part and parcel of the good practice of clinical medicine.

Physicians who work in the field of professional discipline have thought about the limits of propriety in making charges of impropriety. We (R.S.E. and R.S.K.) asked the American Psychiatric Association's Ethics Committee to expand upon its existing commentary on innovative practice and making allegations of professional misconduct. We used the committee's answers to our questions as the basis for the arguments we are making in this piece.

The APA's Ethics Committee uses clear-cut benchmarks to define innovative medical care: "The standards of care ... evolve with evidence from research and observations of practice. Among the expected supports for innovative practice are scientific testing, peer-reviewed publication, replication, and broad or widespread acceptance within a relevant scientific or professional community." When it comes to off-label prescribing for any medical condition, it is easy enough to ascertain whether clinical reports have appeared in peer-reviewed journals.

Two of the biggest blockbusters in psychiatry, chlorpromazine and lithium, began as drugs used for other conditions almost since the inception of our field. In other words, the use of these drugs for mental illness began, in today's jargon, as off-label. We practitioners of psychiatry live in the land of off-label prescribing and have always comfortably done so. In fact, almost all of medicine does. The key in today's world of best-practice medicine is obtaining a truly informed consent.

For COVID-19, our incredible psychotropic molecules may once again be doing some trail-blazing off-label work. Late last year, Eric J. Lenze, MD, professor of psychiatry and director of the Healthy Mind Lab at Washington University in St. Louis, reported in a preliminary study of adult outpatients with symptomatic COVID-19 that those treated with fluvoxamine "had a lower likelihood of clinical deterioration over 15 days," compared with those on placebo (JAMA. 2020;324[22]:2292-300). We were heartened to see Lenze discuss his work on a recent "60 Minutes" segment. David Seftel, MD, MBA, a clinician who administered fluvoxamine as early treatment for a COVID-19 outbreak that occurred in a community of racetrack employees and their families in the San Francisco Bay Area, also was featured. Rather than waiting for the results of large clinical trials, Lenze and Seftel proceeded, based on reports published in peer-reviewed journals, to treat patients whose lives were at risk.

If we find ourselves strongly disagreeing about the science of off-label prescribing, the proper response is to critique methodologies, not the character or competence of colleagues. The APA Ethics Committee discourages use of the media as a forum for making allegations of incompetent or unethical practice: "Judgments regarding violations of established norms of ethical or professional conduct should be made not by individuals but by bodies authorized to take evidence and make informed decisions."

At least one state legislature is taking action to protect patients' access to the doctors they trust. In Arizona, SB 1416 passed in the Senate and is now working its way through the House. This bill would prohibit medical boards from disciplining doctors for speaking out about or prescribing off-label drugs when a reasonable basis for use exists.

Physicians in all specialties would do well to studiously observe the conventions of their profession when it comes to critiquing their colleagues. Psychological research on the "backfire effect" suggests that heavy-handed campaigns to enforce medical consensus will only harden minds in ways that neither advance science nor improve the quality of clinical decision-making.

Medical disciplinary boards and the news media were neither designed nor are they equipped to adjudicate scientific debates. Science is never settled: Hypothesis and theory are always open to testing and revision as new evidence emerges. There is a place in medicine for formal disciplinary processes, as well-delineated by professional bodies such as the APA Ethics Committee. Another important part of protecting the public is to support an environment of scientific inquiry in which diversity of opinion is welcomed. As physicians, we translate science into excellent clinical care every day in our practices, and we advance science by sharing what we learn through friendly collegial communication and collaboration.

Robert S. Emmons, MD, is part-time clinical associate professor in the department of psychiatry at the University of Vermont, Burlington, and is a past chair of the Ethics Committee for the Vermont District Branch of the American Psychiatric Association. He is in private practice in Moretown, Vt., and disclosed no relevant financial relationships. Renée S. Kohanski, MD, is in private practice in Dayton, N.J., and is a diplomate of the American Board of Psychiatry & Neurology. She also is the host and author of Clinical Correlation, a series of the Psychcast. Kohanski disclosed no relevant financial relationships.

This article originally appeared on, part of the Medscape Professional Network.


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