The woman in the television ad tries to pull a grocery shopping cart from a line. It refuses to budge. She yanks with increasing ferocity as her frustration mounts.
"It's that week before your period," a voice intones, "the irritability . . . mood swings . . . bloating. . . . Think it's PMS? Think again. It could be PMDD."
The ad is for Sarafem, a new psychiatric medicine designed to treat premenstrual dysphoric disorder (PMDD), a severe version of premenstrual syndrome said to afflict millions of American women.
Trouble is, psychiatrists haven't decided whether PMDD is real, and the medicine isn't new: Sarafem is the antidepressant Prozac, renamed and repackaged as a pink and lavender capsule.
Sales of Sarafem have soared, spurred by a multimillion-dollar marketing campaign by the drug's maker, Eli Lilly and Co., which is searching for profitable new uses for Prozac. The drug's patent expires in August, and its price is expected to fall.
The campaign has reignited debate over whether PMDD stigmatizes women by characterizing them as having a mental illness once a month, and raised concerns that Eli Lilly's advertising barrage promotes that notion.
"Seeing it over and over legitimizes it. It makes the condition valid when it is not valid and gets in the mind of everybody that this condition is a valid condition," said Sally Severino, a psychiatrist who helped advise the American Psychiatric Association on the disorder. "The more you repeat something, the more you believe it."
Many doctors counter that medicines such as Sarafem help women who suffer severe discomfort, irritability and tension every month. A simple matter of medicine, they say, has been complicated by gender politics, drug marketing and the future of Prozac.
Eli Lilly told shareholders that the launch of Sarafem was tied to the company's preparations for "Year X" -- the company code name for the year patent protection runs out for Prozac, which last year grossed more than $2.6 billion.
"We intend to focus on Prozac in the United States right up to the last day of its exclusivity," Sidney Taurel, chairman and chief executive, said in the 2000 annual report. "And we'll pursue related opportunities . . . [including] Sarafem, a newly introduced brand for women who suffer from premenstrual dysphoric disorder."
Although Prozac's patent expires in August, Sarafem remains protected until 2007 because it is a new application for the chemical. So this fall, if Indianapolis-based Eli Lilly drops the price of Prozac because of competition from generic versions, it could still charge a higher price for Sarafem, although it is the same chemical.
Eli Lilly spokeswoman Laura Miller defended the company's decision to create a new brand name for Prozac, saying that PMDD is a unique disorder. The new packaging provides specific information to doctors about the condition.
"We asked women and physicians, and they told us that they wanted a treatment with its own identity," Miller said. "Women do not look at their symptoms as a depression, and PMDD is not depression but a separate clinical entity. Prozac is one of the more famous pharmaceutical trademarks and is closely associated with depression."
Sarafem costs the same as Prozac -- about $100 a month. Miller would not say whether Eli Lilly planned to price the medicines differently once Prozac lost patent protection. Miller also declined to say how much the company spends marketing Sarafem.
But CMR, a Taylor Nelson Sofres company that tracks advertising and marketing data, said Eli Lilly spent $17 million in direct consumer advertising for Sarafem from October to the end of January. In addition, between the time Sarafem was launched in July through the end of January, the company spent more than $16 million promoting the drug to doctors and in scientific journals, according to IMS Health, a company that tracks the pharmaceutical industry.
Through the end of January, Sarafem had sales of just over $19 million and physicians wrote about 202,000 prescriptions, according to IMS Health.
Eli Lilly pulled the shopping cart ad after the Food and Drug Administration castigated the company in November for marketing the drug too aggressively. The agency said the commercial pitched the medicine to women who had normal PMS and thereby trivialized the seriousness of PMDD. Two new television advertisements were created, and some ads continue to run in women's magazines, Miller said.
The ad campaign has rekindled a debate over PMDD that goes back more than two decades. In the 1980s, the APA considered including PMDD as an official condition in its Diagnostic and Statistical Manual -- the official bible of psychiatric disorders.
The proposal triggered a major controversy. Some women's groups said that calling severe PMS a mental illness might prompt employers to question women's competence or even cause courts to rule against "mentally ill" mothers in custody battles -- a concern that has not materialized.
"Some women get food cravings and breast tenderness [before their period], but when men get mood shifts, no one says let's call it mental illness," said psychologist Paula Caplan, a PMDD critic who wrote the book "They Say You're Crazy."
Medicating women's emotional outbursts, Caplan said, appealed both to women, "who are supposed to be the world's cheerleaders," and to their boyfriends and husbands: "Men who are not supportive are happy to say, 'Yeah baby, something is wrong with you.' "
Many doctors, however, argued that PMDD could be a serious problem that interfered with women's professional and personal lives. Medicine -- long male-dominated -- was right to finally be taking an interest, they said.
The disorder eventually found its way into the appendix of the psychiatrist's manual, placing it in the category of a disorder that is under evaluation.
"There was not sufficient research knowledge to warrant introducing that as a standard, official diagnosis," said Darrel Regier, director of the APA's division of research and an expert on the process by which the APA classifies new disorders.
But last summer, Eli Lilly, armed with research that indicated Prozac could alleviate the symptoms of PMDD, won approval to market the drug for the condition. It was "the first indication for a drug that the Food and Drug Administration has approved for a nonofficial diagnosis," Regier said.
The APA supported the decision -- and Eli Lilly -- for stimulating research into PMDD, because that was the original reason the association put PMDD in the appendix, he said.
Some psychiatrists who helped write the classification, however, said they worried that Eli Lilly's marketing would end up guiding the research, instead of the other way around.
"The cart is before the horse," said Severino, a professor emeritus of psychiatry at the University of New Mexico School of Medicine in Albuquerque. "By classifying it as a depression, it seems to me that treatment will be geared toward depression when we don't know if it is a depression."
It doesn't help that distinguishing PMDD from PMS is difficult. "Unlike any other kind of psychiatric condition, most women believe they have PMS, and most people believe women have PMS," said Nada Stotland, a psychiatrist at Rush Medical College in Chicago who was designated by the APA to speak about PMDD. "We now have a psychiatric disorder with [symptoms] that people believe all women have."
After Eli Lilly launched its advertising campaign for Sarafem as "the first and only prescription medication for PMDD," psychiatrists began fielding frequent requests for the drug from patients.
"Doctors will tell you that the marketing of pharmaceuticals is a mixed blessing," said Wendy Hookman, a psychiatrist who directs the women's mood disorders program at Georgetown University Hospital. Although it helps educate patients to seek treatment, "it can be difficult when a patient gets their mind set that a particular medicine is best for them."
Clinicians such as David Rubinow, clinical director at the National Institute of Mental Health, say that concerns over the disorder are about politics, not science. If a woman was in distress and an effective treatment was available, common sense dictated that she should get help. Several large studies have shown that medicines such as Sarafem are effective in reducing the symptoms of PMS or PMDD. Women typically take Sarafem every day, but it may also be effective when used briefly before periods.
"Abuse is much more likely to derive from the failure of treating clinicians to confirm the diagnosis of what they are treating," Rubinow said. "There is a very high degree of false-positive self-assessments -- people assume they are suffering from PMS or PMDD when, in fact, they are not."
The APA manual recommends that doctors ask women to keep daily journals about their mood states through two menstrual cycles before making a diagnosis. But "we are not a patient society," Stotland said. "People feel they know what they have, and we don't want to step on a woman's authority to say what's going on in her own body."
As a practical matter, asking patients to wait two months may not be realistic, some doctors say.
When Kerry Burke, a 26-year-old management consultant in Alexandria, found herself breaking down and crying before her period -- behavior that she found disruptive to both her job and personal life -- she went to see Hookman. After an hour-long evaluation, Hookman put her on a medication similar to Sarafem and, in a few weeks, Burke reported her symptoms much reduced.
"If a patient is not functioning, if she is saying she is staying home from work because she's afraid she is snapping at her boss and she is going to lose her job, you are not going to keep her out of work for three months before you help her," Hookman said.