Review options in treatment of PMDD

The woman sitting in front of you says for about 10 days of every month, she experiences depression, marked anxiety, sudden mood shifts, persistent irritability, and bloating. While the symptoms disappear with the onset of her menstrual cycle, when they are present they are severe enough to interfere with her relationships and work activities.

What is your diagnosis?

Look at premenstrual dysphoric disorder (PMDD). Both premenstrual syndrome (PMS) and premenstrual dysphoric disorder are marked by the cyclic nature of symptoms that begin in the late luteal phase of the menstrual cycle and remit shortly after the onset of menstruation. PMDD is distinguished from PMS by the severity of symptoms, predominance of mood symptoms, and role dysfunction, particularly in personal relationships and marital/family relationships.1

The Food and Drug Administration (FDA) has issued an approvable letter for Yaz, an oral contraceptive to be manufactured by Berlex Laboratories of Montville, NJ, for treatment of PMDD. Berlex filed for FDA approval of Yaz as an oral contraceptive and as a treatment for the symptoms of PMDD among women who desire contraception, says Kim Schillace, Berlex’s director of public relations. According to Berlex’s parent company, Berlin-based Schering AG, the company anticipates a decision on the drug in the first quarter of 2006.2 If final approval is received, it will represent the first oral contraceptive to carry a PMDD indication.

Yaz contains 20 mcg ethinyl estradiol and 3 mg drospirenone, with a dosing regimen of 24 days of active pills, followed by four days of inactive pills, Schillace reports. To assess its impact in PMDD treatment, researchers conducted a multicenter, double-blind, randomized clinical trial in which 450 women with PMDD symptoms were randomly assigned a placebo pill or the study drug.3 Women in the study were evaluated with interviews, the Daily Record of Severity of Problems (DRSP), and other survey instruments at baseline and through three menstrual cycles. Scientists defined response as a 50% or more decrease in DRSP score; such response occurred in 48% of the active-treatment group and 36% of the placebo group.3

Three drugs carry specific indications for treatment of PMDD: fluoxetine (Sarafem, Eli Lilly; Indianapolis), paroxetine controlled-release (Paxil CR, GlaxoSmithKline; Philadelphia) and sertraline (Zoloft, Pfizer, New York City). Sarafem received its FDA approval in 2000, with PMDD indications given to Zoloft in 2002 and Paxil CR in 2003. The agency gave further approval in 2004 for an intermittent dosing regimen for Paxil CR. The revised labeling allows the drug to be taken once daily during the two-week period prior to the onset of menstrual cycle rather than throughout the month. Research indicates such a dosing regimen is effective against PMDD symptoms.4

There are several reasons that effective treatments for PMDD are needed, says Jean Endicott, PhD, director of the premenstrual evaluation unit at Columbia Presbyterian Medical Center in New York City. Premenstrual symptoms can significantly affect health-related quality of life and may result in increased health care utilization and decreased occupational productivity.5

"First, the symptoms of PMDD are, by definition, severe enough to cause major problems in a woman’s functioning in her social relationships, her work, her parenting, and even taking care of her daily routine tasks," states Endicott. "Second, even though the symptoms are time-limited, occurring during the week to 10 days prior to the onset of menses, they recur over and over for many years and can greatly disrupt a woman’s life."

The consequences of untreated PMDD can be severe. Women are at high risk for developing a period of major depressive disorder if the condition is not addressed, says Endicott.

"Why should a woman be expected to continue to suffer from a condition that is treatable?" observes Endicott. "Women used to be told that nothing can be done, just live with it.’ Now there are a number of effective treatments, and if one does not work, another may."

References

  1. Steiner M, Pearlstein T, Cohen LS, et al. Expert guidelines for the treatment of severe PMS, PMDD, and comorbidities: The role of SSRIs. J Womens Health (Larchmt) 2006; 15:57-69.
  2. Schering AG. FDA clarifies status of YAZ™ PMDD application. Press release. Jan. 25, 2006.
  3. Yonkers KA, Brown C, Pearlstein TB, et al. Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstet Gynecol 2005; 106:492-501.
  4. Pearlstein TB, Bellew KM, Endicott J, et al. Paroxetine controlled release for premenstrual dysphoric disorder: Remission analysis following a randomized, double-blind, placebo-controlled trial. Prim Care Companion J Clin Psychiatry 2005; 7:53-60.
  5. Borenstein JE, Dean BB, Endicott J, et al. Health and economic impact of the premenstrual syndrome. J Reprod Med 2003; 48:515-524.