Management strategies for PMS/PMDD

Journal of Family Practice, Sept, 2004 by Kimberly A. Yonkers

Current guidelines for the diagnosis of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) present challenges for clinicians. The criteria for PMS vary widely. According to the tenth edition of the International Statistical Classification of Diseases and Related Health Problems, for example, criteria include the following heterogeneous symptoms: psychologic discomfort, bloating and weight gain, breast tenderness, foot/hand swelling, aches and pains, poor concentration, sleep disturbance, and change in appetite. Only 1 criterion is necessary for diagnosis. (1) Symptoms do not have to occur during the luteal phase and do not have to be associated with functional impairment. In contrast, the American College of Obstetricians and Gynecologists criteria stipulate that symptoms should occur during the luteal phase and lead to some disturbance in functioning. (2)

As defined by The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), (3) PMDD requires a minimum of 5 symptoms, including at least 1 mood symptom, such as low mood tension, mood swings, or irritability. Symptoms must be confirmed prospectively through daily rating over 2 menstrual cycles and must occur principally during the luteal phase. The symptoms should be evaluated prospectively because data suggest that retrospective reporting is inaccurate. Symptoms also must be present for most cycles and result in some degree of functional impairment in daily life.

Women whose symptoms occur at times other than during their luteal phase are likely to have another disorder such as major depression, dysthymic disorder, or anxiety disorder. These disorders must be distinguished from menstruation-related mood disorders and treated appropriately.

PREVALENCE

Premenstrual conditions can be grouped into 3 broad categories:

* Severe PMDD affects about 2% to 9%, of women.

* Moderate-to-severe PMS affects about 20% to 40% of women. Women with moderate-to-severe PMS have fewer than 5 symptoms but at least 2, and they experience distress associated with the condition. (4)

* Mild PMS may affect up to 80% of women but does not result in functional impairment. (5-8)

TREATMENT STRATEGIES

The onset and duration of symptoms suggest that intermittent, or half-cycle, administration of a selective serotonin reuptake inhibitor may be effective treatment for PMS or PMDD. (9)

Effectiveness of serotonin reuptake inhibitors

The current gold standard, according to evidence-based medicine, for treatment of PMDD is a serotonin reuptake inhibitor (SRI). The SRIs are antidepressant and anxiolytic, and share the property of blocking the serotonin transporter. They may be administered either daily throughout the menstrual cycle or during the second half of the menstrual cycle.

When a woman is treated with an antidepressant agent that is not a SRI, beneficial effects are no greater than what is seen with placebo. With respect to treatment of PMDD, the efficacy of SRIs may be a result of their action in blocking the serotonin transporter, or it might lie in a novel mechanism such as the alteration of progesterone metabolism. The latter is also a characteristic of many medications in this class. (10) A study compared both sertraline (an SRI) and desipramine, a tricyclic antidepressant that does not block the serotonin transporter, with placebo over 3 cycles. Although symptoms were reduced with SRI administration, the improvement shown with desipramine was virtually identical to the placebo response. (11)

In the first systematic, placebo-controlled trial to evaluate SRIs in the treatment of PMDD, 405 women were enrolled in the placebo washout period, with 313 subsequently entering the randomized phase of the study, which lasted 6 menstrual cycles. Of those 313 women, 180 completed the study (FIGURE 1). Participants were randomized to fluoxetine, 20 mg/d or 60 mg/d. After 6 menstrual cycles, women in the active-treatment arm demonstrated a 3- to 4-fold improvement. (12) Subsequent studies confirmed the efficacy of SRIs in treating PMDD, as shown in a meta-analysis of randomized clinical trials (FIGURE 2). (13) (It is important to note here that both selective and nonselective SRIs--eg, clomimpramine--are effective.) Remarkably, the only negative result was reported in a single small trial that did not include daily ratings and had other methodologic problems. (14)

[FIGURES 1-2 OMITTED]

Clearly, SRIs are more effective than placebo, but in clinical trials as many as 35% to 40% of patients feel better on placebo, although this response may be transient. The SRIs also offer a side-effect profile better than that associated with older antidepressants. However, there are some potential side effects that must be managed. The most common complaints include sexual dysfunction, sleep disturbances, and appetite suppression or, alternatively, weight gain. An additional problem is that patients are often reluctant to take psychotropic agents because of the perceived stigma associated with medicine in this class. Such apprehension, as well as side effects, can lead to treatment discontinuation.