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Treatment for PMDD may require some fine tuning. (High Response Seen to SSRIs).

Sertraline recently joined fluoxetine as an approved medication for premenstrual dysphoric disorder, both in intermittent and continuous dosing schedules.

The use of these drugs for this indication is associated with a good response in up to 90% of patients, said Dr. Ted Pearlstein, director of Women's Behavioral Health at the Women and Infants Hospital, Providence, R.I.

Premenstrual dysphoric disorder (PMDD) is defined rather strictly in DSMIV: five or more symptoms during the luteal phase (one of which must be depressed mood, anxiety or tension, affective lability, or anger or irritability) severe enough to markedly interfere with work, school, social activities, or personal relationships. But many clinicians consider a broader spectrum of women as candidates for treatment.

In a community survey of 519 women by Dr. Meir Steiner, director of the Women's Health Concerns Clinic at St. Joseph's Hospital, Hamilton, Ont., 5% of the women satisfied syndromal criteria. But in another 21% who "marginally missed" the criteria, the impact on ability to function was moderate to severe.

"In the past, we've been accused of medicalizing [premenstrual syndrome]," Dr. Steiner explained, with as many as 85% of women said to suffer from it. "The pendulum has swung to the other extreme. Women who are missing one criterion but are severely affected should be treated, and in real life they are."

Dr. Diana Dell, assistant professor of obstetrics and gynecology and psychiatry at Duke University, Durham, N.C., agreed. "If I see a patient with three symptoms [rather than five] and they are disruptive to her life and relationships, I'll treat her, even though it's off label," she said.

Premenstrual exacerbation of depression, anxiety, and other psychiatric or medical conditions is as least as prevalent as true PMDD, and the distinction should be made by tracking mood and other manifestations over two menstrual cycles, Dr. Dell said. Women who keep a record may be surprised to find the symptoms present, albeit at a more manageable level, during the follicular phase.

Charting with a simple, one-page form is highly acceptable to most women. "If a patient mightily objects to it, that's a red flag," said Ellen Freeman, Ph.D., research professor of obstetrics and gynecology and psychiatry at the University of Pennsylvania, Philadelphia. "These usually turn out to be difficult patients, with a lot of other psychiatric and medical problems."

When the diagnosis is PMDD, intermittent dosing is the regimen of first choice for Dr. Dell and Dr. Steiner: It makes physiologic sense and is less likely to cause troublesome side effects. But patient preference must be considered, Dr. Freeman said. "For every woman who just wants to take medication premen-strually, another can't be bothered to remember when to start and feels better if she takes it all the time," she added.

In intermittent dosing, Dr. Pearlstein adheres to the schedule used in clinical trials--the last 2 weeks of the cycle, ending when menstruation begins. "I don't believe that symptom-onset dosing is as effective."

But in Dr. Dell's experience, many women spontaneously individualize their schedule, taking the drug at the onset of symptoms and discontinuing it when experience has told them symptoms end. On the whole, they do well.

Just two selective serotonin reuptake inhibitors (SSRIs) have been approved for this indication, but response to the others seems comparable. In general, Dr. Steiner said, daily doses in the low end of the antidepressant range are adequate: 10-20 mg of fluoxetine, 25-50 mg of sertraline, 10-20 mg of paroxetine, or 1020 mg of citalopram. When symptoms are severe or respond just partially to the lower dose, an increase often helps. A switch to another SSRI also can help, he said.

Some women do better with a slightly higher dose for the last few days of the cycle, when symptoms are most severe, Dr. Pearlstein said. Low as-needed doses of an anxiolytic such as alprazolam or buspirone may similarly close the gap in tough cases.

Continuous dosing may help if the intermittent regimen is not working. Poor response to intermittent therapy may suggest the existence of a subsyndromal mood disorder throughout the menstrual cycle.

In general, a poor response to SSRI therapy should prompt a reconsideration of the diagnosis, including a thorough work-up for medical problems, Dr. Freeman said.

"Just about anything can be worse premenstrually," she said.

An underlying depression or anxiety disorder may be addressed with the same medications, but on a continuous schedule, Dr. Dell said. A woman already under treatment for one of these disorders might benefit from a slightly increased dosage during the luteal phase. Alternatively, if she is taking a nonserotonergic agent (such as bupropion), consider adding an SSRI.

PMDD is a chronic disorder that tends to worsen with age, so treatment is likely to be necessary until the menopause. Many women have substantial symptom exacerbations during the perimenopause.

The situation during perimenopause is likely to be complicated by irregular menses. A low-dose oral contraceptive (if not contraindicated) may in itself relieve symptoms, Dr. Steiner said. In any case, it will regulate the cycle, making a trial of intermittent SSRI treatment feasible.
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Author:Sherman, Carl
Publication:Internal Medicine News
Date:Dec 15, 2002
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