premenstrual dysphoric disorder

**Definition/DSM-5 criteria:** In most menstrual cycles during the past year, ≥5 symptoms occur in the final week before menses, begin to improve within a few days after menses onset, and are minimal or absent in the week post-menses. At least 1 symptom must be from each of these groups, as follows. (1) Core affective symptoms (≥1): marked affective lability, marked irritability/anger, markedly depressed mood/hopelessness, or marked anxiety/tension. (2) Additional symptoms (to reach 5 total): decreased interest in usual activities, difficulty concentrating, lethargy/fatigue, appetite change/food cravings/overeating, hypersomnia or insomnia, feeling overwhelmed/out of control, and physical symptoms (breast tenderness or swelling, joint/muscle pain, bloating, weight gain). Symptoms must cause clinically significant distress or functional impairment. They must not be an exacerbation of another disorder (e.g., MDD, persistent depressive disorder, panic disorder) and are not attributable to a substance or medical condition. Diagnosis requires confirmation by **prospective daily symptom ratings for at least 2 symptomatic cycles** (provisional diagnosis may be made before confirmation).

**Pathophysiology:** The cause is not fully understood. The leading hypothesis is an abnormal central sensitivity to normal cyclical fluctuations of ovarian hormones (estradiol and progesterone), not abnormal hormone levels. Hormone levels in affected women are generally normal. A key mediator is allopregnanolone (a progesterone metabolite and positive allosteric modulator of GABA-A receptors), with altered GABA-A receptor response. Serotonergic dysregulation is also implicated, which explains the rapid response to SSRIs. Symptoms occur only in ovulatory cycles and resolve with ovulation suppression, pregnancy, and menopause.

**PMS vs PMDD:** PMS is common (~20–30% of women with bothersome symptoms) and has mild to moderate symptoms without major functional impairment. PMDD affects ~3–8% of reproductive-age women and has severe symptoms with marked impairment. Both are limited to the luteal phase. Mood symptoms must be prominent in PMDD.

**Differential:** MDD or dysthymia with premenstrual exacerbation (symptoms persist throughout the cycle, so check for symptom-free follicular weeks), bipolar disorder, anxiety/panic disorder, thyroid disease, perimenopause, anemia, and substance use. Prospective charting separates PMDD from these because PMDD has a symptom-free interval after menses.

**Management:** - **First line:** SSRIs (fluoxetine, sertraline, paroxetine, citalopram). They act within days, unlike the weeks required in MDD, and can be given continuously or only during the luteal phase (from ovulation to menses onset). - **Also used:** Combined OCPs containing drospirenone (a spironolactone analog with anti-mineralocorticoid/antiandrogenic activity; FDA-approved for PMDD with ethinyl estradiol, in the 24/4 regimen), especially if contraception is also desired. - **Refractory cases:** GnRH agonists (e.g., leuprolide) with add-back therapy. Bilateral oophorectomy is a last resort. - **Adjuncts:** CBT, exercise, calcium supplementation (and possibly vitamin B6), and a diet low in caffeine, alcohol, and salt. Spironolactone may help with bloating.

**Board pearls:** PMDD is under "Depressive Disorders" in DSM-5. The timing is a luteal-phase onset that remits within days of menses onset. Diagnosis requires prospective daily symptom charting for 2 cycles. First-line therapy is SSRIs, which work quickly and can be dosed intermittently. Drospirenone-containing OCPs are an alternative. Suicidality risk is elevated in severe PMDD, so screen for it.