to the editor: I was dismayed by the article on excessive daytime sleepiness, a malady that its author says “affects an estimated 20 percent of the population.” Excessive daytime sleepiness has been actively promoted as a disease for at least five years. In 2004, Cephalon, Inc., the manufacturer of modafinil (Provigil), sponsored a “guideline” authored by doctors with links to the pharmaceutical industry.¹ Before this, excessive sleepiness was a little-known term to primary care physicians.

By publishing this review, American Family Physician (AFP) is arguably complicit in a practice known as disease mongering, described as “the selling of sickness that widens the boundaries of illness and grows the markets for those who sell and deliver treatments,”² or that leads to the “pharmaceuticalization of everyday life.”³

Excessive daytime sleepiness is not recognized by the American Academy of Sleep Medicine's International Classification of Sleep Disorders. However, efforts have been made to link this “concept of illness” to modafinil through journal advertising, continuing medical education, journal articles, expert opinion, supplements, and other forms of marketing. In 2008, Provigil achieved blockbuster status, with more than $1 billion in sales in the United States.

Modafinil is approved by the U.S. Food and Drug Administration (FDA) only for sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder. However, using a common disease-mongering strategy, modafinil was heavily marketed off-label. In 2008, Cephalon pleaded guilty to promoting modafinil for uses not approved by the FDA and was fined $444 million. The FDA also admonished Cephalon in 2002 for promoting unapproved uses of the drug, including as a pharmaceutical aid for “sleepiness, tiredness, decreased activity, lack of energy, and fatigue.”⁴

I am concerned that the AFP article closely links modafinil and the treatment of persistent daytime sleepiness in the Strength of Recommendations Taxonomy table.

In his author disclosure, Dr. Pagel reported no conflicts of interest. However, as recently as 2005, he publicly disclosed that he is a member of four industry speaker panels, including one for Cephalon.⁵ In 2008, he published an article in a supplement sponsored by Cephalon and disclosed that he is on the speakers bureau of Sepracor, Inc., the maker of another blockbuster sleep drug.⁶ Does this conflict of interest violate AFP's policy? If so, why were Dr. Pagel's conflicts not discovered before publication?

As family physicians, we must be aware that disease mongering is an important industry marketing technique. And although a drug company may simply be acting in the best interests of its shareholders, we as family physicians should act in the best interests of our patients and reject this practice.

in reply: Excessive daytime sleepiness is not shyness, laziness, a lack of motivation, or an example of disease mongering. In contrast, it is a serious medical and medico-legal problem associated with an increased propensity for motor vehicle accidents, reduced work and school performance, and the medically serious diagnosis of sleep apnea. Excessive daytime sleepiness can have major deleterious effects on general health and mortality. People can die when they fall asleep driving. In a PubMed search, the phrase “excessive daytime sleepiness” identifies 1,714 scientific articles. Rare hits in the primary care literature focus on the extent to which this symptom is under-recognized, yet it is highly prevalent. A North Carolina Family Practice Research study showed that more than 50 percent of adult patients of the clinic reported excessive daytime sleepiness on a patient questionnaire.¹ Contrary to Dr. Brown's contention, the American Academy of Sleep Medicine emphasizes the importance of excessive daytime sleepiness (hypersomnolence) using an entire spectrum of International Classification of Diseases (ICD)-II diagnostic codes, including: obstructive sleep apnea with hypersomnolence, 327.23; hypersomnolence with short sleep time, 327.10; behaviorally induced insufficient sleep syndrome, 307.44; and hypersomnolence due to drug or substance, 327.14.²

My article was written at the request of the editors of American Family Physician (AFP) for an article on problem sleepiness/excessive sleepiness, and emphasizes repeatedly the association of excessive daytime sleepiness with underlying diagnoses. I received no drug company support or any other support for writing this article, and had no potential conflicts of interest in the year leading up to submission. The article on obstructive sleep apnea-induced sleepiness cited by Dr. Brown was published in a supplement to the Journal of Family Practice that was supported by Cephalon.³ I received no funding for this article; however, I did receive manuscript preparation assistance, and I acknowledge that I should have filed an updated conflict of interest statement with the Washington, DC, editorial office of AFP documenting this relationship. During the period after these papers were accepted for publication, I also developed a relationship with the speaker's panel at Sepracor, the makers of eszopiclone (Lunesta), which is used in the treatment of insomnia. Although neither insomnia nor hypnotic medications were discussed in my AFP article, apparently this relationship could be construed as a potential conflict of interest.

Although this paper focuses on diagnosis and non-drug therapy for patients affected by significant daytime sleepiness, one paragraph does address the use of medications to treat daytime sleepiness. My initial submission discussed modafinil (Provigil) as an alternative option to treatment with generic medications such as dextroamphetamine and methylphenidate (Ritalin). However, after one of the AFP reviewers stated, “I am particularly concerned about the recommendation, however guarded, for the use of amphetamines,” the empahsis of that paragraph was altered to more strongly support the use of modafinil.

Dr. Brown apparently thinks excessive daytime sleepiness is not a legitimate medical condition with potentially serious consequences. I respectfully disagree.

editor's note: The American Family Physician (AFP) conflict of interest policy states: “ AFP will not consider manuscripts sponsored directly or indirectly by a pharmaceutical company, public relations firm, or other commercial entity, or those written by an author with a financial interest in a company that makes a product discussed in the manuscript or a competing product.”¹

This policy is mentioned in our author's guide, the letter we send to authors of solicited or proposed articles, and in the conflict of interest form that authors must sign when they submit a manuscript.² The form asks for disclosure of relationships “within 12 months of the date of this form and within the foreseeable future.” It also states: “If you develop new financial interests in or arrangements with a relevant organization after the time you completed this author disclosure form and submitted your manuscript, but prior to publication, please update your form and send it to our editorial office in Washington, DC. Changes in such affiliations might preclude your paper from publication.”²

After receiving Dr. Brown's letter, our internal investigation revealed the following:

1. Dr. Pagel did not have any conflicts to report when he wrote or submitted his paper. He had ended his previous relationships with drug companies a little over two years before submitting his manuscript, and our conflict of interest disclosure form asks authors to report relationships within the previous 12 months.

2. During the year between the acceptance of his article and its publication, Dr. Pagel redeveloped relationships with Cephalon and Sepracor, and published an article³ in a journal supplement that was supported by Cephalon, and for which he received manuscript preparation assistance from Anthemis Consulting, Ltd., a medical communications company that assists pharmaceutical companies in producing clinical content relevant to drugs they manufacture.

Had we known about these relationships before publication, we would have withdrawn the article from our production schedule. However, because the article has already been published, and because the National Library of Medicine recommends not removing published articles from their online status,⁴ we are publishing this clarification of disclosure and have updated the disclosure status of the online version of this article.

We will also revise our conflict of interest policy and form, and ask that authors disclose financial relationships within 36 (rather than 12) months of manuscript submission, as well as within the foreseeable future.

The philosophy behind our conflict of interest policy is simple: to avoid bias, or the perception of bias, we want articles written by authors who have no ties to industry. We feel that to do otherwise runs the risk of producing biased clinical content or, worse, providing marketing messages disguised as continuing medical education.⁵ Although we do not think the content of Dr. Pagel's article is biased, we are publishing this notice in order to correct the disclosure statement and to highlight our conflict of interest policy.