Bumps in the Night

The Accutane story is all scare, and no science.

In the movie One-Eyed Jacks, Marlon Brando asks Marshall Karl Malden if he'll get a fair trial. "Oh sure, kid, sure," answers Malden, soothingly. "You're gonna get a fair trial. And then I'm gonna hang you! Personally!"

That pretty much sums up how everybody–but the patients themselves–have treated Roche Laboratories' acne drug Accutane.

Recently the capsules were back in the news after a 15-year-old St. Petersburg, Florida boy named Charles Bishop stole a light plane and flew it into the 28th floor of a 42-story Tampa building. A sample of the media coverage:

* CNN Live Today: "Tampa Authorities Say They Found Acne Drug Accutane at Home of Teen Pilot Charles Bishop"

* ABC's Good Morning America: "Charles Bishop May Have Used Accutane before Crash"

* United Press International: "Teen Pilot Had Accutane Prescription"

* Newsday: "Pilot's Acne Drug Linked to Suicides"

* And this one says it all, from London's "The Mirror: Plane Boy Drugs Link "

More bizarre yet: Police found a note on Bishop's body expressing sympathy for Osama bin Laden and support for the September 11 attacks.

Clearly something was troubling this young man, but it wasn't Accutane. As only a handful of media outlets bothered to report a week later, an autopsy showed no trace of the drug in the boy's system.

Nonetheless, the story will add to the undeservedly bad reputation of a drug used by 5 million Americans and 7 million others worldwide since 1982 to combat one of the most disfiguring forms of acne, the "severe recalcitrant nodular" variety. Yet there's no evidence linking the drug to so much as a single suicide (much less support for international terrorism) unless you count non-causal associations, rumor, innuendo, and the efforts of lawyers and politicians.

Three things quickly sent Accutane down the road to infamy, despite clear evidence of its tremendous benefits to users. The first is that it was known from the beginning that Accutane is a powerful teratogen, meaning it causes birth defects. It's been labeled as such since its introduction, and Roche has worked aggressively (albeit not completely successfully) to prevent any woman who might possibly be pregnant or become so soon from getting a prescription.

Medically, teratogenicity has nothing to do with depression or thoughts of suicide. But this gave the drug immediate notoriety. From its launch, doctors were keeping a sharp eye out for any other possible serious side effect and reporting those possible connections to the FDA under its adverse event reporting system (AERS).

"When there's public awareness or publicity about a drug for any reason, there may be an increase in reports because people may not have otherwise thought about associations," points out FDA spokeswoman Kathleen Kolar. Nevertheless, she immediately adds that while "Accutane is safe and effective when used as directed, any drug that has had that many warnings does merit concern."

Hmm . . . In any case, this concern led the FDA to require that Roche warn on the drug's label that it may cause "depression, psychosis, suicidal ideation, suicide, and attempts at suicide." This in turn no doubt has and will lead to more adverse event reports.

Indeed, according to Roche spokeswoman Gail Safian, the Tampa incident is being reported to the FDA as an Accutane-related suicide, notwithstanding that there's no evidence Bishop ever took the drug. All the stories that fingered Accutane in his death will probably lead to more adverse reports.

The second association between Accutane and suicide is that the drug is used primarily by people whose age group is especially prone to suicide. According to the U.S. Centers for Disease Control and Prevention in Atlanta, for persons "15-24 years old, suicide is the third leading cause of death, behind unintentional injury and homicide."

And the problem is getting worse. "From 1952-1995, the incidence of suicide among adolescents and young adults nearly tripled," says the CDC. "From 1980-1997, the rate of suicide among persons aged 15-19 years increased by 11% and among persons aged 10-14 years by 109%." Accutane, introduced in 1982, arrived about 30 years too late to have been the cause of this increase.

The third association between Accutane and suicide is that researchers have found what appears to be a cause-and-effect link between even mild acne and depression. You might expect that Clearasil users have a higher rate of suicide. Nevertheless, while the overall rate of suicide in the general population is about 11.1 per 100,000; that of Accutane users, according to a Roche survey, is 1.8 per 100,000. There have been about 90,000 U.S. suicides since 1982 compared to 167 FDA adverse reports for Accutane-related suicides.

Moreover, nobody has found any kind of biological plausibility for how Accutane might even cause depression. The active ingredient in Accutane (isotretinoin) is a Vitamin A derivative and overdoses of Vitamin A can be toxic. But there is no evidence that hypervitaminosis A can cause psychiatric reactions.

Another important contributor to the hysteria are the sharks in suits. After all, suicide cases are natural heart-tuggers and you never know when you'll get lucky before a judge or jury. If you go to a Web site with an innocuous-sounding name like http://www.accutane_suicide_help.com/ you'll find you've actually come across a lawyer-referral service.

It's indicative of the weak case against Accutane that one of the most powerful indictments came from the allegations of a single man with no medical background and a powerful motive to lay blame. In late 2000, the son of Rep. Bart Stupak (D-Mich.) committed suicide. As do so many grieving parents whose children have taken their own lives, Stupak sought desperately for a reason. What he found was that Bart Jr. had been taking Accutane.

Stupak's accusation, though, didn't just go to the FDA; it was broadcast in his own press conference, in which the lawyer and former state trooper took on the role of both forensic specialist and epidemiologist. This in turn led to House hearings, plenty more media coverage, and no doubt more adverse event reports.

So it has been and always will be for Accutane. Bad publicity leads to more bad publicity which leads to even more bad publicity. It is a vicious cycle from which Accutane and Roche will never escape. There's a valuable lesson in here; but don't expect that anyone will learn it.