GAITHERSBURG -- The Food and Drug Administration's (FDA) Psychopharmacologic Drugs Advisory Committee on Wednesday voted unanimously to recommend approval of Eli Lilly's Prozac (fluoxetine) for treatment of premenstrual dysphoric disorder (PMDD), defined as a severe form of premenstrual syndrome (PMS).
For this indication, the drug may be sold with different packaging and
under a different name than Prozac. Lilly has asked FDA to allow a new name, and
is waiting for an answer, according to the company.
If the FDA follows the panel's advice, Prozac would be the first drug ever
approved for PMDD, estimated to affect 3% to 5% of menstruating women. But
panelists said the drug should not be prescribed for premenstrual syndrome
(PMS), which affects 80% of menstruating women.
Lilly said its two pivotal trials, and a third supportive study, showed
that Prozac significantly reduced symptoms of depression and irritability around
the time of menstruation, and improved women's ability to interact socially.
The company said the drug also reduced physical symptoms such as bloating
and breast tenderness, but panelists were a bit skeptical of this claim.
Primary investigator Meir Steiner of McMaster University in Hamilton,
Ontario, said the drug was so effective that patients' husbands inundated his
clinic with flowers after completion of his study several years ago.
"Clinically, this was so impressive, it was almost unbelievable," Steiner said.
"Most of the patients got totally better."
Much of the panel discussion revolved around whether PMS and PMDD are
distinctive disorders, and how PMDD could be diagnosed.
The company said PMDD is distinctive from other psychological disorders,
and defined it as a more severe form of PMS. While panelists agreed that PMS and
PMDD are recognizable, they debated whether PMDD could be accurately diagnosed,
especially by general practitioners.
"In my practice, I don't see any distinction between PMDD and PMS," said
Susan Thys-Jacobs, a committee consultant from St. Luke's-Roosevelt Hospital
Center.
Lilly consultant Jean Endicott of Columbia University said PMDD is
dominated by mood disturbances such as extreme irritability, depression and
anxiety, and is present in the week before onset of menstruation. Symptoms,
which also include physical problems like breast tenderness, always resolve with
menstruation, but reappear with the next cycle, Endicott said.
PMDD is described as a disorder in the appendix of the Fourth edition of
the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), and certain
criteria have to be met to make the diagnosis. The FDA may include the criteria
in labeling of the drug, said Bob Temple, FDA director of medical policy.
Endicott argued that PMDD, in its worst form, has an impact on women's
lives equal to that of major depression. "It is quite impairing and occurs every
cycle," she said.
Committee members also debated whether it was safe to give Prozac
continuously -- as Lilly did in trials -- and not just for a week or two before
the start of a period. Most said that with no data to support intermittent use,
continuous dosing would have to be accepted. In an ongoing trial, Lilly is
studying giving the drug to women 14 days before the onset of menstruation.
