Luteal-phase antidepressant an option in recalcitrant PMS, PMDD



SAN FRANCISCO – Selective serotonin reuptake inhibitor antidepressants can alleviate symptoms of premenstrual syndrome or premenstrual dysphoric disorder, but are far from first-line therapies for either disorder, according to Dr. Ellen Haller.

The first steps in treating PMS and PMDD are basic wellness strategies such as a healthy diet, smoking cessation, exercise, adequate sleep, and stress management, Dr. Haller said at a conference on women’s health sponsored by the University of California, San Francisco.

Dr. Ellen Haller

Calcium supplementation also has been shown to reduce total emotional and physical symptom scores by 48% in women with PMS compared with a 30% reduction from placebo in a multicenter, randomized placebo-controlled study of 497 patients. That study used 600 mg, twice daily, of calcium carbonate or placebo for three menstrual cycles, said Dr. Haller, professor of clinical psychiatry at the university.

The results of that study (Am. J. Obstet.Gynecol. 1998;179:444-52) have not been replicated, she added.

If wellness treatments and calcium supplementation don’t work, the next step for treating women with PMS may be an SSRI. A Cochrane review of 31 randomized controlled trials found that SSRIs are more effective than placebo in treating PMS (Cochrane Database Syst. Rev. 2013;6:CD001396). Treatment should be an SSRI antidepressant, Dr. Haller emphasized. Bupropion, which is a norepinephrine dopamine reuptake inhibitor, is not effective for these women.

Low-dose SSRIs may be taken daily or can be effective against emotional and physical symptoms if taken only during the luteal phase of menstruation, starting on day 14 of the cycle and stopping on day 1, the first day of menses, Dr. Haller said. Patients with PMS tend to respond more quickly and at lower doses than patients with depression, and usually don’t get withdrawal symptoms when stopping the SSRI on the luteal-phase dosing regimen.

In women with PMDD, there is a preliminary suggestion that an SSRI may be more effective than calcium supplements. A pilot study of 39 women with PMDD found that the SSRI fluoxetine was more effective than calcium or placebo for PMDD, though scores were significantly better than calcium only on just two of five symptom scales. The study compared fluoxetine 10 mg b.i.d., calcium carbonate 600 mg b.i.d., and placebo (J. Clin. Psychopharmacol. 2013;33:614-20).

Dr. Haller also advised avoiding progesterone-only or other combination oral contraceptives, most of which can worsen PMDD symptoms. The oral contraceptive Yaz (drospirenone 3 mg plus ethinyl estradiol 20 mcg) is an evidence-based option that is approved to treat PMDD.

In a double-blind, randomized placebo-controlled trial, 450 women with rigorously diagnosed PMDD spent 24 days on Yaz or placebo and 4 days on an inert pill per cycle for three menstrual cycles. The Yaz group had a significant 47% decrease in total symptom scores compared with a 38% decrease in the placebo group. Side effects, most commonly nausea and intermenstrual bleeding, prompted 15% on Yaz and 4% on placebo to drop out of the study (Obstet. Gynecol. 2005;106:492-501).

Significant PMS symptoms affect approximately 30% of women, but PMDD affects perhaps 3%-8%. PMDD typically starts in a woman’s 3rd decade (in her 20s) and worsens over time, Dr. Haller said. PMDD is a formal diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). The illness reduces quality of life and level of functioning during the late luteal phase of the menstrual cycle, affecting relationships, work, or school.

"We miss this diagnosis a lot of the time," she said. Missed diagnosis rates for PMDD are estimated to be as high as 90%.

Conversely, approximately 40% of patients who think they have PMDD actually experience premenstrual exacerbations of bipolar disorder, major depression, anxiety, or other psychiatric disorders with symptoms that can get worse during the late luteal phase.

To diagnose PMDD, first rule out other psychiatric disorders and other medical disorders such as hypothyroidism, Dr. Haller advised. Then, have patients prospectively record their symptoms on a daily symptom diary to track associations with the menstrual cycle.

Dr. Haller reported having no relevant financial disclosures.

On Twitter @sherryboschert

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