FDA Panel Recommends Fluoxetine for PMDD

Surveys indicate that from 3 percent to 8 percent of North American women in their reproductive years suffer from premenstrual dysphoric disorder (PMDD).

The Food and Drug Administration’s (FDA’s) Psychopharmacologic Drugs Advisory Committee has recommended that the FDA approve an indication for fluoxetine (Prozac) in the treatment of PMDD.

On November 3 Prozac-manufacturer Eli Lilly and Company announced the advisory panel’s unanimous recommendation. The FDA rarely rejects the advisory panel’s recommendations, and if approved, Prozac will be the first drug specifically indicated for PMDD.

The disorder afflicts from 3 percent to 8 percent of North American women in their reproductive years, according to an article published in the New England Journal of Medicine in June 1995. PMDD is characterized by dysphoria, tension, and irritability linked to the menstrual cycle. PMDD is in an appendix of the DSM-IV reserved for criteria needing further study, observed Judith Gold, M.D., former chair of APA’s Work Group on Late Luteal Phase Dysphoric Disorder, the name by which PMDD was formerly known.

"PMDD is still in the appendix and so is still a candidate for further research," she noted. But Gold added that "there has been quite a bit of research since DSM-IV came out showing that the SSRIs are quite effective" in treating PMDD.

The research includes studies on fluoxetine and sertraline (Zoloft) showing that "they are effective in controlling the mood disorder symptoms of PMDD in about 60 percent of patients who meet the PMDD criteria," said Gold. "There is a fairly sizable group, however, that don’t improve." That finding suggests that there may be varying etiologies for PMDD, she said.

Several studies conducted within the last few years have found that intermittent dosing with the SSRIs is effective in relieving the symptoms of PMDD, observed Gold. This suggests that women with PMDD "don’t have to take the medication constantly, but just in the premenstrual period," she said.

Another interesting finding is that the mood symptoms of PMDD are alleviated by lower doses of SSRIs than those normally used in treating depression, said Gold.

Diana Dell, M.D., who chairs the Women’s Caucus of the APA Assembly, is trained in obstetrics-gynecology and psychiatry. "It is likely that this will be the first of the SSRIs to be approved for this use," said Dell. "All of us in clinical practice have been using these drugs off-label this way for 10 years."

The agents used have included Prozac and the other SSRIs with "good results, whether used intermittently or continuously" and at lower doses than those used to treat depression, said Dell. "All of those drugs were developed during a time when including women and ethnic minorities in clinical trials had not been mandated," Dell added. "It doesn’t surprise me that lower doses are often effective in treating women."

The advisory panel’s recommendation is hoped to "presage greater attention to the development of diagnostic criteria and clinical treatments focused on gender-specific disorders," Dell commented. The terminology surrounding premenstrual dysphoria has changed over the years, she noted, but "the notion that PMDD is a more severe subset of PMS is far more palatable than that it is an entirely separate disorder."

"We are pleased with the [FDA] committee’s [recommendation] and look forward to continuing an ongoing dialogue with the FDA to obtain approval to market fluoxetine to treat PMDD," said Rajinder Judge, M.D., Lilly Research Laboratories’ director and global physician for fluoxetine.

In a press release on the advisory committee’s recommendation, Lilly said that although the etiology of PMDD is not clearly established, it "could be caused by an abnormal biochemical response to normal hormonal changes." Routine changes in estrogen and progesterone associated with menses may, in vulnerable women, induce a serotonin deficiency that could trigger the symptoms of PMDD.

The Lilly statement further notes that the course of PMDD differs from both major depression and premenstrual syndrome (PMS). "Major depression is episodic, and its symptoms can persist for weeks, months, or years." It is not linked to the menstrual cycle, the statement notes. PMDD is associated with more severe symptomatology and greater functional impairment than PMS, the statement notes.