Premenstrual symptoms are common among reproductive-aged women. Mild to moderate symptoms are reported in up to 75% of women with severe symptoms and functional impairment (PMDD) affecting 3-8%. A comprehensive assessment of symptoms, including prospective daily symptom ratings for at least two consecutive menstrual cycles is needed to make the diagnosis of premenstrual dysphoric disorder. While patients are recording or “charting” their symptoms across the menstrual cycle, clinicians may encourage patients to engage in healthy lifestyle interventions (diet and exercise) as well as undergo trials of calcium supplementation (1200 mg daily) and/or use of vitamin Bs 50-100 mg daily. While patients may express interest in herbal medications, it is important to keep in mind that the majority of positive studies have been open trials. Moreover, most alternative and complementary treatments, such as St. John’s Wort, relaxation, massage therapy and magnesium, do not have demonstrated efficacy for treatment of premenstrual dysphoric disorder.

If the patient does not respond to the initial interventions and a diagnosis of severe premenstrual syndrome or premenstrual dysphoric disorder is confirmed with the prospective ratings, a trial of an SSRI should be initiated. The most appropriate dosing method (intermittent or luteal phase vs. continuous administration) remains uncertain. However, recent data and clinical experience suggest that the initial antidepressant trial should be one utilizing a luteal phase or intermittent dosing strategy (Table Intermittent (Luteal) SSRI/SNRI dosing strategies for premenstrual dysphoric disorder). Because ovulation testing may be too burdensome and costly, it is reasonable for patients to begin taking the prescribed SSRI two weeks prior to the expected onset of menses, which should approximate onset of the luteal phase. Patients should complete a course of at least three cycles on this medication prior to considering an alternate treatment strategy. Typically, patients will begin to notice a reduction in symptoms within three to five days of medication therapy with luteal phase dosing. However, some patients may require several cycles before noticing any significant change. There are no current data to support switching to a different SSRI if the initial one fails or moving from luteal phase to continuous dosing strategies. Nevertheless, clinical experience suggests that these two strategies may be utilized in the event of an initial treatment failure. Therefore, if the patient does not demonstrate any improvement in her symptoms after several luteal phase treatment cycles, it is reasonable to begin a trial of an alternate SSRI for three cycles with luteal phase dosing if the patient has been compliant with this regimen. Alternatively, the patient may be tried on the same or a different SSRI with continuous dosing.

Table Intermittent (Luteal) SSRI/SNRI dosing strategies for premenstrual dysphoric disorder

SSRI/SNRI Starting Dose (mg) Therapeutic Dose (mg) Discontinuation Effects1
Fluoxetine 10 202 Same as placebo
Sertraline3 50 50-100 Headache, nausea, dry mouth, sexual dysfunction
Paroxetine CR 12.5 12.5-25 Nausea, asthenia, dizziness reduced libido, diarrhea, sweating, tremor4
Venlafaxine 75 75-112.5 Headaches, vivid dreams, sweating, muscle cramps, insomnia

1) Luteal phase administration of SRI/SNRIs have not demonstrated significant side effects with initiation or discontinuation with each cycle. Agents with shorter T1/2 may be more likely to produce mild to moderate discontinuation effects. The controlled trials of these agents did not demonstrate increased drop-out rates for active medication compared to placebo. 2) Fluoxetine 20 mg was more effective than 1 0 mg for the management of premenstrual physical symptoms. 3) Intermittent sertraline did not demonstrate significant improvement compared to placebo for physical symptoms. 4) Side effects were seen more often in patients on paroxetine CR 25 mg compared to 12.5 mg.

The most appropriate duration of pharmacological treatment for premenstrual dysphoric disorder has not been determined. Studies have demonstrated a return of symptoms after discontinuation of treatment with a faster return of symptoms in patients with brief treatment duration. Therefore, following the demonstration of a positive response to treatment, it is currently recommended for the patient to remain on the effective dose for at least 12 months.

With better identification of patients with premenstrual dysphoric disorder and appropriate diagnostic verification, clinicians will improve the quality of life for women with severe premenstrual symptoms. Enhanced physician, patient and public education about premenstrual dysphoric disorder may foster more research in the area, which should lead to improved understanding of premenstrual dysphoric disorder and to the development of more specific therapies.

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