PMDD Medication Options
Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacologic treatment for premenstrual dysphoric disorder, with sertraline 50-150 mg/day being FDA-approved and demonstrating superior efficacy over placebo in reducing mood, behavioral, and physical symptoms. 1
First-Line Treatment: SSRIs
SSRIs have established efficacy as first-line agents for PMDD, with multiple agents showing benefit 2, 3, 4:
- Sertraline: FDA-approved at 50-150 mg/day, can be dosed either continuously throughout the menstrual cycle or limited to luteal phase dosing (last 2 weeks before menses) 1
- Fluoxetine: 10-20 mg/day, FDA-approved for PMDD 5, 2
- Paroxetine: 12.5-25 mg/day (controlled-release formulation), FDA-approved for PMDD 5, 2
- Escitalopram: 10-20 mg/day 2
- Citalopram: Effective in clinical trials 6
Dosing Strategies
Two evidence-based dosing approaches exist 1, 6:
Continuous daily dosing: Start at 50 mg/day sertraline throughout the entire menstrual cycle, with dose adjustments up to 150 mg/day based on response 1
Luteal phase dosing: Initiate treatment 2 weeks before expected menses at 50 mg/day, discontinue at menses onset; can increase to 100 mg/day in subsequent cycles if needed (with 3-day titration at 50 mg/day) 1, 7
Intermittent luteal phase dosing offers advantages including reduced long-term side effects, lower cost, and decreased risk of discontinuation syndrome while maintaining 75% response rates 6, 7. However, continuous dosing may be preferred for patients with more severe symptoms 3.
Second-Line Pharmacologic Options
If SSRIs fail or are not tolerated, consider 2, 3:
- Venlafaxine (SNRI): Demonstrated efficacy in depressive disorders with anxiety features 5
- Duloxetine (SNRI): Effective for mood disorders 5
- Alprazolam: Low-dose intermittent luteal phase administration as second-line option 3, 6
- Buspirone: Alternative anxiolytic option 3
Hormonal Interventions
Drospirenone-containing oral contraceptives (ethinyl estradiol 20 mcg + drospirenone 3 mg, 24 days active/4 days inactive) represent a first or second-line option depending on patient preference and contraceptive needs 2. Ovulation suppression eliminates premenstrual symptoms but requires careful benefit-risk assessment 4.
GnRH agonists and danazol may be considered when other treatments fail, but serious side effects and cost limit use to short periods 6.
Non-Pharmacologic Adjuncts
Calcium supplementation (1200 mg/day) has demonstrated consistent therapeutic benefit and should be recommended 3.
Cognitive behavioral therapy (CBT) shows effectiveness in reducing functional impairment, depressed mood, anxiety, mood swings, irritability, and symptom severity 2. CBT can be used as monotherapy for milder cases or combined with SSRIs for more severe presentations 2, 3.
Treatment Algorithm
Start with SSRI monotherapy (sertraline 50 mg/day, either continuous or luteal phase dosing based on symptom severity and patient preference) 1, 2. Add calcium supplementation 1200 mg/day 3.
If inadequate response after 2-3 menstrual cycles: Increase SSRI dose (sertraline up to 150 mg/day for continuous dosing or 100 mg/day for luteal phase) 1.
If still inadequate response: Switch to alternative SSRI (fluoxetine, paroxetine, escitalopram) 3, 6.
If SSRIs fail or not tolerated: Consider SNRI (venlafaxine, duloxetine) or drospirenone-containing oral contraceptive 2, 3.
Refractory cases: Trial of alprazolam (luteal phase), buspirone, or referral for GnRH agonist consideration 3, 6.
Critical Considerations
Distinguish PMDD from premenstrual syndrome (PMS) and premenstrual exacerbation of underlying psychiatric disorders through prospective daily symptom charting for at least 2 menstrual cycles 4, 6. PMDD requires marked functional impairment and symptom-free intervals in the follicular phase 1.
Monitor for treatment-emergent suicidality, particularly in adolescents and young adults, as black box warnings exist for SSRIs 5.
Dose adjustments should not occur more frequently than weekly given sertraline's 24-hour elimination half-life 1.
For luteal phase dosing at 100 mg/day, always use a 3-day titration period at 50 mg/day at the beginning of each dosing cycle to minimize side effects 1.