What is the recommended treatment for Premenstrual Dysphoric Disorder (PMDD)?

Treatment of Premenstrual Dysphoric Disorder (PMDD)

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacologic treatment for PMDD, with drospirenone-containing oral contraceptives as an FDA-approved alternative specifically for women who also desire contraception. 1

First-Line Treatment Approach

SSRIs as Primary Pharmacotherapy

• SSRIs are established as first-line treatment with proven efficacy for PMDD symptoms 2, 3, 4
• FDA-approved SSRIs include:
  • Sertraline 50-150 mg/day 5, 6
  • Fluoxetine 10-20 mg/day 5, 3
  • Paroxetine (controlled-release) 12.5-25 mg/day 5, 3
  • Escitalopram 10-20 mg/day 5

Dosing Strategies for SSRIs

• Continuous daily dosing, luteal phase dosing, or symptom-onset dosing are all effective options 2, 4
• Symptom-onset dosing (starting at symptom onset through first few days of menses) demonstrated efficacy with sertraline, showing significant improvement on depressive symptoms (5.14-point difference on IDS-C, P=.02) and anger/irritability subscales 6
• Luteal phase dosing (half of menstrual cycle) is effective and may reduce side effects compared to continuous dosing 4
• Abrupt cessation with symptom-onset dosing was not associated with discontinuation symptoms 6

Hormonal Treatment: Drospirenone/Ethinyl Estradiol

• FDA-approved specifically for PMDD treatment when the patient has already decided to use oral contraceptives for birth control 1
• Dosing: drospirenone 3 mg + ethinyl estradiol 20 mcg daily for 24 days, followed by 4 inactive days 5
• Should NOT be initiated solely for PMDD treatment if the patient does not desire contraception, as other therapies exist without the cardiovascular risks of combined hormonal contraceptives 1
• Critical contraindications: kidney, liver, or adrenal disease due to potassium-sparing effects that could cause serious cardiac complications 1
• Requires potassium monitoring during first month if patient takes NSAIDs long-term, potassium-sparing diuretics, ACE inhibitors, angiotensin-II receptor antagonists, or aldosterone antagonists 1

Second-Line and Adjunctive Treatments

Alternative Psychotropic Medications

• Venlafaxine and duloxetine (SNRIs) have demonstrated efficacy for PMDD 2
• Alprazolam (benzodiazepine) is recommended by the American College of Physicians but must be used cautiously due to dependence risk 7, 2
• Buspirone has shown benefit for PMDD symptoms 2

Symptomatic Relief

• NSAIDs are recommended by the American Academy of Family Physicians specifically for physical pain symptoms in PMDD 7, 3
• Spironolactone can be used as supportive care for bloating and fluid retention 3

Non-Pharmacologic Interventions

• Regular aerobic exercise is recommended by the American College of Sports Medicine as a first-line treatment option for mild-to-moderate PMDD symptoms 7
• Cognitive behavioral therapy (CBT) showed positive results in reducing functional impairment, depressed mood, anxiety, mood swings, irritability, and conflict with others 5
• CBT may reduce: feelings of hopelessness, sensitivity, insomnia, impact on daily life, and symptom intensity 5

Supplementation

• Calcium supplementation has demonstrated consistent therapeutic benefit across studies 2, 3
• Other supplements (chasteberry/agnus castus, St. John's wort) have unclear or conflicting evidence and require more rigorous study 3, 4

Treatment Algorithm

1. For all patients: Recommend lifestyle modifications and regular aerobic exercise as baseline interventions 7

2. For mild-to-moderate symptoms:

   • Start with exercise and lifestyle modifications 7
   • Consider calcium supplementation 2
   • Consider CBT if available 5

3. For moderate-to-severe symptoms requiring pharmacotherapy:

   • If patient desires contraception: Drospirenone/ethinyl estradiol (after screening for contraindications and ensuring potassium monitoring) 1
   • If patient does not desire contraception or has contraindications to hormonal therapy: SSRI as first-line (sertraline, fluoxetine, paroxetine, or escitalopram) 5, 3
   • Choose between continuous, luteal phase, or symptom-onset dosing based on patient preference and symptom pattern 4, 6

4. If inadequate response to first SSRI: Switch to alternative SSRI or consider SNRI (venlafaxine, duloxetine) 2

5. Adjunctive treatments:

   • NSAIDs for physical pain symptoms 7
   • Anxiolytics (alprazolam, buspirone) if anxiety predominates, with caution regarding dependence 7, 2

Critical Safety Considerations

• Monitor for treatment-emergent suicidality when initiating SSRIs, particularly in adolescents and young adults, as SSRIs carry black box warnings 7
• Screen for cardiovascular risk factors before prescribing drospirenone/ethinyl estradiol, especially smoking status in women over 35 (absolute contraindication) 1
• Verify renal, hepatic, and adrenal function before initiating drospirenone due to potassium-sparing effects 1
• Assess for drug interactions that increase potassium when considering drospirenone 1

Common Pitfalls to Avoid

• Do not confuse PMDD with premenstrual syndrome (PMS); PMDD requires more severe symptoms causing significant functional impairment 1, 5
• Do not prescribe drospirenone/ethinyl estradiol solely for PMDD treatment without contraceptive intent, as safer alternatives exist 1
• Do not assume all antidepressants require continuous daily dosing; intermittent dosing strategies are effective for PMDD unlike major depressive disorder 4, 6
• Do not overlook the efficacy of non-pharmacologic interventions, particularly exercise and CBT, which may be sufficient for mild-to-moderate cases 7, 5