There are no studies that examine maintenance treatment in women with PMDD and a comorbid psychiatric illness. PMDD is a chronic, recurrent disorder, so it can be assumed that long-term treatment is indicated. Further studies are warranted.
Alprazolam, a benzodiazepine, and buspirone, a 5-HT1A agonist, have shown modest efficacy in some, but not all, PMS studies. Berger and Presser29 found a poorer response to alprazolam in women with follicular phase anxiety and depression than in those with only luteal phase symptoms. Women took the medication regularly during the luteal phase and on an as needed basis during the follicular phase.
If a woman continues to experience significant premenstrual anxiety, despite treatment with an SSRI, luteal phase treatment with an anxiolytic can be considered.
Estradiol affects 5-HT synthesis and reuptake. Pharmacological suppression of ovulation has been shown to decrease symptoms in women with PMS. Young and colleagues30 reported in the analysis of the STAR*D that 1238 women with depression who took a combined oral hormonal contraception (OCP) report less severe depression. Yet, many women reported increased mood and anxiety symptoms while taking synthetic progestins; this needs to be carefully considered in women with comorbid Axis I disorders. OCPs in general do not improve PMS symptoms, although there may be benefit to the FDA-approved use of the OCP that contains drosperinone 3 mg and ethinyl estradiol 20 µg (DRSP/EE) or extended-cycle dosing (fewer hormone-free intervals). In an open-label trial, Joffe and associates31 found that an OCP that contains DRSP/EE given to women with prospectively diagnosed PME of depression was effective. Again, the possible effects of OCPs on women with an underlying mood disorder need to be considered.
Among the most effective hormonal treatments for PMS suppression is the gonadotropin-releasing hormone (GnRH) agonist leuprolide, which is administered by monthly injection in depot form, and intranasal buserelin. GnRH agonists decrease pituitary release of follicle-stimulating hormone and luteinizing hormone, thereby suppressing ovulation. One key note about the treatment of comorbid depression and PMDD is that the GnRH agonists are less effective when there is an underlying depressive disorder.32 In addition, GnRH agonists can be difficult for patients because of the resulting hypoestrogenism. Adverse effects of GnRH treatment include hot flashes, headaches, and osteoporosis.
Grigorova and colleagues33 reported a significant increase in Beck Depression Inventory scores in 26 previously asymptomatic women after 4 weeks of treatment with leuprolide. The mood-related adverse effects of a GnRH agonist should be monitored closely in all women; this is especially important in women who are predisposed to mood disorders.
Calcium carbonate reduces premenstrual depression, fatigue, edema, and pain significantly more than placebo in women with PMS.34 Although there are no data in women with Axis I comorbidity and PMDD, calcium is a reasonable first-line choice for women with mild PMS symptoms or as an adjunct for women with moderate to severe PMS. Calcium should be used carefully in patients with constipation or renal stones.
Table 2 describes the steps to diagnose PMDD or PME in the context of another psychiatric disorder.
In patients with PMDD there is a 30% to 70% and a 14% to 16% lifetime risk of major depression and anxiety, respectively. Patients with PMDD need to be screened for depression and anxiety and vice versa. There are few data to guide treatment in these patients, but the use of SSRIs should be considered first-line with various dosing strategies to increase effectiveness.
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