How are Premenstrual Dysphoric Disorder (PMDD) symptoms managed?

Management of Premenstrual Dysphoric Disorder (PMDD) Symptoms

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PMDD, with sertraline 50-150 mg/day, fluoxetine 10-20 mg/day, escitalopram 10-20 mg/day, or paroxetine 12.5-25 mg/day being the most effective options. 1, 2

Core Symptom Profile

PMDD is characterized by a pattern of mood symptoms (depressed mood, anxiety, affective lability, persistent anger), somatic symptoms (breast tenderness, headache, joint/muscle pain, bloating, weight gain), and cognitive symptoms (forgetfulness, difficulty concentrating, lack of energy) that begin several days before menses, improve within a few days after menses onset, and become minimal or absent within 1 week following menses onset. 3 The disorder affects 3-8% of menstruating women and represents the severe, disabling end of the premenstrual disorder spectrum. 4

First-Line Pharmacologic Treatment: SSRIs

SSRIs are established as the gold standard for PMDD management based on their ability to reduce emotional, cognitive-behavioral, and physical symptoms while improving psychosocial functioning. 5, 6

Dosing Strategies

• Luteal phase dosing (administering medication only during the 2 weeks prior to menses onset) is as effective as continuous daily dosing for PMDD, unlike depression treatment where daily administration is required. 1, 4, 5
• Sertraline administered in the late luteal phase at 50-100 mg/day (with patients titrated to 100 mg/day receiving 50 mg/day for the first 3 days, then 100 mg/day for the remainder of the cycle) demonstrated significant superiority over placebo on symptom reduction. 1
• Continuous daily dosing throughout the menstrual cycle (sertraline 50-150 mg/day) is also effective and may be preferred for patients with more severe symptoms. 1

Specific SSRI Options

• Sertraline: 50-150 mg/day (mean effective dose 102-146 mg/day for completers in clinical trials). 1, 2
• Fluoxetine: 10-20 mg/day. 2
• Escitalopram: 10-20 mg/day. 2
• Paroxetine: 12.5-25 mg/day. 2
• Citalopram: Effective when used intermittently during the luteal phase. 5

Treatment Duration

The effectiveness of sertraline for PMDD beyond 3 menstrual cycles has not been systematically evaluated in controlled trials; however, since symptoms commonly worsen with age until menopause, continuation of treatment in responding patients is reasonable. 1 Dosage adjustments between regimens (daily throughout cycle versus luteal phase only) may be needed to maintain patients on the lowest effective dose. 1

Second-Line Pharmacologic Options

Combined Oral Contraceptives

Drospirenone-containing oral contraceptives (ethinyl estradiol 3 mg and drospirenone 20 mg/day for 24 days of hormonal pills, 4 days inactive) are effective as first or second-line treatment depending on patient preference and contraceptive needs. 2

Other Psychiatric Medications

If SSRIs fail, consider:

• Venlafaxine (SNRI): Demonstrated efficacy for PMDD. 6
• Duloxetine (SNRI): Useful alternative. 6
• Alprazolam (low-dose, luteal phase only): Second-line option, but limited to short-term use due to dependence risk. 5, 6
• Buspirone: Alternative anxiolytic option. 6

Refractory Cases

For patients who fail multiple SSRI trials and oral contraceptives:

• GnRH agonists: Effective but limited by cost and serious side effects; restrict to short treatment periods. 5, 7
• Danazol: May be considered but carries significant side effect burden. 5
• Surgical intervention (bilateral oophorectomy): Reserved for severe, treatment-refractory cases. 7

Non-Pharmacologic Treatments

Cognitive Behavioral Therapy (CBT)

CBT demonstrates positive results in reducing functional impairment, depressed mood, hopelessness, anxiety, mood swings, irritability, insomnia, interpersonal conflict, and symptom handicap. 2 CBT effectively reduces the functional impact of PMDD and may become first-line treatment as more evidence accumulates. 2

Nutritional Supplementation

• Calcium supplementation: The only supplement with consistent demonstrated therapeutic benefit for PMDD. 6
• Omega-3 fatty acids: May be considered as complementary option but lacks strong evidence specifically for PMDD and is not recommended as standalone treatment. 8

Other Complementary Approaches

• Chasteberry (Agnus castus): May be useful adjunct but evidence is limited. 4
• St. John's wort (Hypericum perforatum): Potential adjunct with limited substantiation. 4
• Acupuncture and yoga: Some evidence of efficacy but variability in study quality limits definitive recommendations. 7

Treatment Algorithm

1. Initiate SSRI therapy (sertraline 50 mg/day as starting dose, titrate to 50-150 mg/day based on response). 1, 2
2. Choose dosing strategy: Luteal phase dosing (cost-effective, reduces long-term side effects and discontinuation syndrome risk) versus continuous daily dosing (may be better for severe symptoms). 5
3. If first SSRI fails after 2-3 cycles: Switch to another SSRI from the list above. 5
4. If multiple SSRIs fail: Consider drospirenone-containing oral contraceptive or alternative psychiatric medications (venlafaxine, duloxetine, low-dose luteal phase alprazolam). 6, 2
5. Add CBT at any stage to enhance treatment response and address functional impairment. 2
6. For refractory cases: Trial of GnRH agonist or referral for surgical consultation. 5, 7

Critical Considerations

• Distinguish PMDD from premenstrual syndrome (PMS): PMDD requires marked functional impairment and specific DSM-5 criteria; PMS involves milder symptoms. 2
• Rule out premenstrual exacerbation of underlying mood disorders: Ensure symptoms remit with menses rather than persisting throughout the cycle. 1, 4
• Monitor for serotonin syndrome: When combining SSRIs with other serotonergic agents or MAOIs, allow appropriate washout periods (at least 14 days). 1
• Luteal phase dosing advantages: Reduces medication cost, minimizes long-term side effects, and decreases risk of SSRI discontinuation syndrome compared to continuous dosing. 5
• Calcium supplementation: Can be recommended as adjunct therapy given consistent evidence and minimal risk. 6