IN ONE CASE, DRUGS OK’D BEFORE DISORDER
Drug company influence, money play role, probe finds
Beginning in 2000, the FDA approved four drugs to treat premenstrual dysphoric disorder, a form of PMS said to be so severe that it qualifies as a psychiatric condition.
The hitch: It wasn’t even recognized as a mental disorder until 13 years after first drug treatments were on market.
The drug approvals started less than two years after an unusual private meeting involving six officials from the U.S. Food and Drug Administration and four executives from Eli Lilly. The drug company’s lucrative patent on the antidepressant Prozac was about to expire and the executives had a new market in mind.
The 1998 meeting in Washington, D.C., was funded by Lilly and included 16 researchers exploring the condition, called PMDD.
There was strong disagreement over the condition, which the American Psychiatric Association had determined needed more study before it could be included in its manual defining mental disorders and symptoms.
That didn’t stop the meeting participants.
On their own, they determined PMDD was a distinct clinical disorder and declared that a class of antidepressant drugs known as selective serotonin reuptake inhibitors — a group including Pro- zac — were effective at treating it.
Eight months later, the researchers wrote a paper summing up their findings and describing the process that led to them. It was published in a medical journal affiliated with an organization that had gotten money from Lilly in the past.
Lilly rebranded Prozac, changing the pill’s colors from green and yellow to pink and purple, and giving it a more femininesounding name — Sarafem. Sarafem won FDA approval. It wouldn’t be until 2013 that the American Psychiatric Association formally recognized PMDD as a distinct psychiatric condition — a determination that was based on the recommendation of a panel on which nearly 70% of the members had drug company ties.
By then, drug companies had created a major new market built on a disputed condition, inflated estimates of how many women had it and drugs that carry severe risks and side effects, such as suicidal thinking.
Conclusions from that 1998 meeting were presented as a consensus. But one participant whose name appears on the paper said she never agreed that PMDD was a mental condition or that antidepressants should be used to treat it.
To this day, Sally Severino, an emeritus professor of psychiatry at the University of New Mexico, said she holds an opposite view. There never has been convincing
evidence to prove either contention, she said.
DRUGS FIRST, DISORDER SECOND
A Milwaukee Journal Sentinel/ MedPage Today investigation into the emergence of PMDD found evidence of drug company influence — and money — at virtually every step along the way. It is one of a series of new disorders promoted by drug companies and treated with expensive, often dangerous, drugs.
What stands out about PMDD is that so much of the effort to promote the condition began long before it was recognized as a psychiatric disorder.
Start with that 1998 meeting, paid for by Lilly.
On its face, the meeting — which over the years has received scant public attention — was unusual.
Lilly spokesman J. Scott MacGregor said a check of company records showed the meeting was called after Lilly met with FDA officials “who suggested it would be useful” to convene experts to determine if PMDD was a distinct disorder.
In an email, FDA spokeswoman Lauren Shaham defended the agency’s participation in the meeting and noted that a public discussion of the condition was held about a year later at the official FDA meeting on whether to approve Sarafem.
Critics say it is unusual for a small group of doctors to independently determine what is or is not a medical or psychiatric condition.
Allen Frances, chairman of the American Psychiatric Association panel that in 1994 had decided not to elevate PMDD to an official condition, said he was “puzzled” at the time about the FDA approval of the drug. The condition, he said, “wasn’t ready for prime time.”
In an interview, he said it was “absolutely absurd for the FDA, in secret meetings with drug companies, to make a decision that would be contrary” to what the psychiatric community had decided about PMDD.
Similarly, guidelines to help doctors decide how to treat PMDD were issued before the condition was even recognized as a psychiatric disorder.
Typically such guidelines are issued by medical societies or other groups. In this case, the 2006 guidelines were issued by a small group of researchers and paid for by GlaxoSmithKline — the maker of Paxil.
The guidelines proclaimed antidepressants, such as Paxil, were “the treatment of choice” for PMDD.
While the guidelines did not disclose financial conflicts of the eight authors, at least six are known to have worked for companies that make drugs used to treat PMDD, according to a Journal Sentinel/MedPage Today analysis of other published work by the authors.
At the time the FDA was considering Sarafem for approval, estimates claimed as many as 8% of premenopausal American women had PMDD, a figure that would represent about 6 million women.
But independent researchers say those calculations are flawed.
Even before it was formally recognized, the criteria for PMDD said a woman must have at least five of 11 symptoms, such as feeling angry, irritable, depressed or anxious, and having mood swings.
Sarah Gehlert, of the Institute of Public Health at Washington University in St. Louis, said she was suspicious that the various estimates were not following the definition.
In 2009, Gehlert’s team studied 1,247 women from rural and urban communities in Illinois and Missouri and followed them through two menstrual cycles to determine if they met the criteria.
The finding: Only 1.3% of premenopausal women may have PMDD in any given year.
That means just under 1 million women in the United States, not 6 million.
“We did become convinced that some women had PMDD,” Gehlert said, “but we could also see that it had the potential to harm women if it became a quick-and-dirty diagnosis.”
Even before it was formally recognized, the criteria for PMDD said a woman must have at least five of 11 symptoms.
John Fauber is a reporter for the Milwaukee Journal Sentinel. Kristina Fiore and Matthew Wynn are reporters for MedPage Today.
This story was reported as a joint project of the Journal Sentinel and MedPage Today, which provides a clinical perspective for physicians on breaking medical news at medpagetoday.com.
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