What medications are used to treat Premenstrual Dysphoric Disorder (PMDD)?

Medications for Premenstrual Dysphoric Disorder (PMDD)

Selective Serotonin Reuptake Inhibitors (SSRIs) are the first-line treatment for PMDD, with sertraline being the most strongly recommended option due to its favorable efficacy and side effect profile. 1, 2

First-Line Treatments

SSRIs

SSRIs have the strongest evidence for treating PMDD and should be considered the gold standard treatment. They work rapidly for PMDD symptoms, unlike their delayed effect in depression.

• Sertraline: 50-200mg daily (starting at 25-50mg) 1
• Fluoxetine: 10-20mg daily 3
• Escitalopram: 10-20mg daily 3
• Paroxetine: 12.5-25mg daily 3

SSRIs can be administered in three different ways:

1. Continuous daily dosing (every day of the menstrual cycle) - most effective approach 2
2. Luteal phase dosing (from ovulation to menses) - less effective but still beneficial 2
3. Symptom-onset dosing - requires further research 4

A 2024 Cochrane review found that continuous administration is probably more effective than luteal phase dosing (P = 0.03 for subgroup difference) 2.

Second-Line Treatments

Oral Contraceptives with Drospirenone

• Drospirenone/Ethinyl Estradiol: 3mg DRSP/20μg EE for 24 days, followed by 4 days of inactive pills 5, 3

Drospirenone-containing oral contraceptives have demonstrated efficacy for PMDD in clinical trials. The FDA has approved this combination for PMDD treatment in women who choose to use an oral contraceptive for birth control 5.

Other Antidepressants

If SSRIs are ineffective or not tolerated:

• Venlafaxine (SNRI) 1, 6
• Duloxetine (SNRI) 6

Common Side Effects to Monitor

SSRI treatment increases the risk of adverse events, with the most common being:

• Nausea (NNTH: approximately 7 patients) 2
• Insomnia 2
• Sexual dysfunction 2
• Fatigue 2
• Dizziness 2

For drospirenone-containing contraceptives, monitor potassium levels in patients with risk factors for hyperkalemia 5.

Treatment Algorithm

1. Initial Assessment:

   • Confirm PMDD diagnosis using DSM-5 criteria
   • Rule out other mood disorders or medical conditions

2. First-Line Treatment:

   • Start with sertraline 25-50mg daily, preferably using continuous dosing
   • Titrate up to 50-200mg based on response and tolerability

3. If Inadequate Response After 2-3 Cycles:

   • Switch to another SSRI (fluoxetine, escitalopram, or paroxetine)
   • Consider changing from luteal phase to continuous dosing if using intermittent dosing

4. If Still Inadequate Response:

   • Consider drospirenone/ethinyl estradiol if contraception is also desired
   • Or try an SNRI like venlafaxine

Important Considerations

• PMDD significantly interferes with work, school, and relationships, causing marked mood disturbances including depression, anxiety, mood swings, and irritability 5
• Physical symptoms may include breast tenderness, headache, joint/muscle pain, bloating, and weight gain 5
• Treatment should be continued for at least 2-3 menstrual cycles to properly assess efficacy
• Unlike PMS, PMDD requires proper diagnosis by healthcare providers due to its severity 5

Common Pitfalls to Avoid

• Misdiagnosis: Ensure proper differentiation between PMDD and PMS (less severe) or other mood disorders
• Inadequate treatment duration: Allow sufficient time (2-3 cycles) to assess treatment efficacy
• Inappropriate dosing: Using depression dosing schedules rather than PMDD-specific protocols
• Overlooking contraindications: Particularly for drospirenone in patients with kidney, liver, or adrenal disease 5
• Premature discontinuation: Patients may need long-term treatment to maintain symptom control

The goal of treatment should be complete remission of symptoms, not just partial improvement, to restore quality of life and functioning 1.