April 2, 1999

Whether or not premenstrual dysphoric disorder, or PMDD, is a bona fide disorder is an ongoing controversy that will be resolved only by further research, according to Judith Gold, M.D.

Gold, who chaired the DSM-IV Work Group on PMDD, discussed the data surrounding PMDD at the annual meeting of the American College of Psychiatrists (ACP) in San Francisco in February.

PMDD is currently listed in the main text of DSM-IV as a differential diagnosis under "depressive disorder not otherwise specified." Differential diagnoses are those referred to when major diagnoses are not applicable, explained Gold. But it remains in the appendix of "criteria sets and axes provided for further study."

Putting PMDD in the appendix of DSM-IV "has been most effective," said Gold. "As a consequence, studies are now easier to interpret because the patients used in the studies have their diagnoses confirmed using PMDD criteria. Therefore the results can be understood and studies replicated. In the past, a group of people with poorly defined premenstrual syndrome (PMS) would be used. Since it was impossible to know what criteria had been used for the definition, the data were difficult to interpret and the studies difficult to replicate."

The PMDD controversy revolves around stigma and fears that according PMDD full status as a disorder would contribute to the denigration of women as cyclically impaired by their menstrual cycle, said Gold. Critics have been particularly concerned about a diagnosis limited to women, arguing that paternalistic male physicians already tend to minimize women's complaints and might more easily tend to classify women as emotionally disturbed given a specific female-only disorder.

These fears are best mitigated through further research elucidating women's symptoms and following established diagnostic definitions and guidelines, according to Gold. In a discussion of PMDD in the DSM-IV Sourcebook, Gold remarked that "leaving PMDD in the appendix emphasizes that further studies are essential to validate the disorder and that these studies should focus on defining the biochemical foundation of this depressive disorder."

Although PMDD, by definition, occurs only in women, "a similar cyclical disorder has not been looked for in men and thus could exist," Gold commented. Further research that validates a cyclical mood disorder, "whether affecting both women and men or either, will enable the development of effective treatment and stimulate more research on its etiology," she concluded.

Recent studies have shown response rates to selective serotonin reuptake inhibitors (SSRIs) of between 60 percent and 70 percent among women diagnosed as suffering from PMDD. Other clinical trials have confirmed that PMDD sufferers respond to lower doses of SSRIs than those normally used for depression and to intermittent dosing, Gold noted.

Also, the literature suggests that there is a subset of women who experience premenstrual magnification of both depressive and anxiety symptoms.

"The response to SSRIs and tryptophan indicate commonality with mood disorders," said Gold. In a study published in the February Biological Psychiatry researchers found that tryptophan, which appears to increase serotonin synthesis, had a beneficial effect on some patients with PMDD, Gold observed.

There is, however, "a sizable percentage of people who meet PMDD criteria who do not respond to SSRIs," said Gold, and this points to a "varying etiology of the disorder and suggests it would be useful to look at nonresponders."

Hormonal cycles only precipitate the syndrome in susceptible women; they do not cause it, Gold asserted. Although there are strong data supporting PMDD as a diagnosis, they did not meet "the level set for new diagnoses to be included in DSM-IV," Gold said.

There is no clear evidence of a common genetic link between PMDD and major depression, and one study has concluded that there is no link, according to Gold. The state of knowledge on the relationship between mood disorders and PMDD is "suggestive but tentative," said Gold. "Maybe what we have is a common pathway that manifests with mood-disorder-like symptoms, but the underlying pathology that begins the chain of events may be different from that of recognized mood disorders," Gold commented. "That's my personal speculation, having reviewed the literature."

Regardless of the political controversy and the need for further research, clinicians should be aware of the possibility that a woman presenting with cyclical depression may be suffering from PMDD and should inquire about the timing in relation to menses, said Gold. Clinicians need "to recognize that PMDD was included as a differential diagnosis for depression to alert physicians to the fact that a very small number of women do develop" significant depressive symptoms linked to the menstrual cycle that are not present in the follicular phase.

Only one survey, conducted in 1990 with a relatively small sample of college-aged women, has looked at PMDD incidence. That survey found about 4 percent of college-aged women met criteria for the disorder. But the methodology and lack of clarity of definitional criteria at the time call for a new prevalence study, said Gold.