What treatments work for PMDD?

Premenstrual dysphoric disorder (PMDD) is a cyclic mood disorder affecting a subset of women in the late luteal phase, marked by severe affective and physical symptoms that resolve with menses. It is distinguished from milder premenstrual syndrome (PMS) by symptom severity and functional impairment. PMDD causes substantial distress: women with PMDD have functional impairments comparable to other depressive disorders and increased work absences, and PMDD is associated with higher rates of suicidal ideation and attempts. First-line pharmacotherapy consists of selective serotonin reuptake inhibitors (SSRIs) and hormone-based treatments. SSRIs (e.g. sertraline, fluoxetine, paroxetine, escitalopram) are effective when dosed continuously or in the luteal phase, often producing rapid symptom relief at low doses. Hormonal therapies (e.g. combined oral contraceptives with drospirenone/ethinyl estradiol, GnRH agonists with add-back) can mitigate symptoms by suppressing cyclic ovarian hormone fluctuations. Emerging treatments target PMDD’s neuroendocrine underpinnings: for example, sepranolone (an allopregnanolone antagonist) has shown promising early results. Novel approaches under investigation include neurosteroid modulators, anti-inflammatory strategies, and personalized interventions (genetic or biomarker-driven therapy). This review summarizes current evidence-based pharmacotherapies for PMDD and discusses emerging treatment avenues based on advances in PMDD neurobiology and psychoneuroendocrinology.

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