May 9, 2006
By DANIEL CARLAT
THAT pharmaceutical companies pay doctors to say good things about their drugs is no longer newsworthy. Two former editors of The New England Journal of Medicine, Jerome P. Kassirer and Marcia Angell, have documented the drug industry's use of doctors to promote new medicines through professional articles and at medical conferences.
But in a move that may astonish even the most jaded critics of ethically challenged pharmaceutical marketing, makers of sleeping pills are now paying doctors to publish bad things about competing drugs.
The market for sleeping pills is huge — 42 million prescriptions were filled last year — and it is more competitive than ever, thanks to the recent introduction of Sepracor's Lunesta (the one with the butterfly commercials), Sanofi-Aventis's Ambien CR (a controlled-release version of Ambien) and Takeda Pharmaceuticals' Rozerem. Ads have made most of these drugs household names. Yet many people have never heard of one of the most widely prescribed hypnotics in the United States: trazodone.
First approved by the Food and Drug Administration 25 years ago, trazodone is categorized as an antidepressant. Nonetheless, psychiatrists prescribe it off label to treat insomnia, because it works so well. Trazodone carries no risk of addiction; its half-life is long enough to keep patients asleep all night; it has a long safety record; and it is cheap, costing as little as 10 cents a pill. (Ambien and Lunesta can cost $3 a pill or more.) And in the only sizable study to compare trazodone with Ambien as a sleep aid, the two drugs performed equally well.
But each time a psychiatrist prescribes trazodone, a potential sale of Lunesta or Ambien is lost. No doubt that is why, in the past few years, several articles have been published in professional journals that can only be described as trazodone-bashing. With titles like "The Use of Trazodone as a Hypnotic: A Critical Review" (published in The Journal of Clinical Psychiatry), these articles purport to present balanced reviews of the scientific literature on sleeping pills. But the authors, psychiatrists with university affiliations, have been paid by Sepracor, Sanofi-Aventis or Takeda, the companies that stand to gain from trazodone's downfall.
A disclosure statement at the top of one such paper, "A Review of the Evidence for the Efficacy and Safety of Trazodone in Insomnia," also in The Journal of Clinical Psychiatry, states that Sepracor "assisted in the preparation" of the article, and paid the author a fee for "the services he provided in support of the development" of the manuscript.
A careful reading of these articles reveals a pattern of rhetorical techniques: a minimization of trazodone's advantages and an emphasis on its negative qualities.
Trazodone is criticized as lacking high-quality research data on its ability to help people sleep. What is left unmentioned is that because trazodone is no longer patented, no pharmaceutical company stands to profit from doing such research.
The authors also dust off older studies highlighting side effects from trazodone, like cardiac arrhythmias or priapism (prolonged painful erections). But these side effects are extremely rare: priapism has been found to occur in one in 5,000 men who take the drug, and the incidence of cardiac arrythmias is even lower.
Case reports of such side effects inevitably surface when a drug has been on the market for 25 years. In the case of Ambien, the oldest of the newer drugs, we are already seeing a flurry of reports of problems like drug abuse, sleepwalking, night eating and car accidents that may be associated with its use.
The way to discourage this practice of negative marketing disguised as legitimate scientific commentary is to mandate fuller disclosure of links between drug companies and authors. Several states now insist that drug makers report the gifts they give doctors.
These same companies should be required to disclose the exact nature of a doctor's involvement in preparing a sponsored article, as well as the dollar amount of his or her fee. I suspect it would be the rare doctor who would want such information to come to light.
Daniel Carlat, a professor at Tufts Medical School, is the editor in chief of The Carlat Psychiatry Report.