In an adult woman of reproductive age with premenstrual dysphoric disorder and no contraindications to SSRIs, which is the better first‑line option: sertraline or escitalopram?

Sertraline or Escitalopram for PMDD

For premenstrual dysphoric disorder, sertraline is the preferred first-line SSRI because it has FDA approval specifically for PMDD (including luteal-phase dosing), robust evidence demonstrating efficacy in this population, and proven tolerability with intermittent administration. 1, 2

Evidence-Based Rationale

FDA Approval Status

• Sertraline holds FDA approval for PMDD treatment in both continuous and luteal-phase administration regimens, making it the regulatory standard for this indication 1
• Escitalopram lacks FDA approval for PMDD, though it has been studied in preliminary trials 3

Clinical Efficacy in PMDD

Sertraline:

• Demonstrated 50% responder rate versus 26% placebo in luteal-phase dosing (P <.001) by the first treatment cycle 2
• Effective at flexible doses of 50-100 mg/day during the luteal phase (last 2 weeks of menstrual cycle) 2
• Produces significant improvement in Daily Record of Severity of Problems scores (27.6 vs 17.6 placebo, P <.002) 2
• Well-tolerated with only 8% discontinuation due to adverse events, and no discontinuation symptoms reported with intermittent administration 1, 2

Escitalopram:

• Only preliminary evidence exists from a small study (N=27) showing 57% improvement with luteal-phase dosing and 51% with symptom-onset dosing 3
• Doses of 10-20 mg/day were used, but this represents limited evidence compared to sertraline 3
• Women with more severe PMDD symptoms responded better to luteal-phase dosing than symptom-onset dosing 3

Practical Dosing Advantages

Sertraline offers flexible administration options:

• Luteal-phase dosing (50-100 mg/day for 14 days before menses) reduces medication exposure and treatment costs compared to continuous administration 1, 2
• Can also be given continuously at 50-150 mg/day if luteal-phase dosing proves insufficient 4
• Sertraline may require twice-daily dosing at low doses in some patients, though typically once-daily administration suffices 5

Escitalopram considerations:

• Maintains consistent once-daily dosing at all doses 5
• Has the lowest propensity for drug-drug interactions among SSRIs due to minimal CYP450 effects 5, 6

Clinical Algorithm for PMDD Treatment

First-Line Approach

1. Start sertraline 50 mg daily during luteal phase only (days 14-28 of cycle, or from ovulation to menses onset) 1, 2
2. Titrate to 100 mg if inadequate response after 1-2 cycles 2
3. Expect response by first treatment cycle in 50% of patients 2

When to Consider Escitalopram Instead

• Patient taking multiple medications with significant CYP2D6 interactions (sertraline has moderate CYP2D6 inhibition) 5, 6
• Elderly patients requiring polypharmacy where drug interaction risk is paramount 6
• Previous intolerance to sertraline specifically 4

If Luteal-Phase Dosing Fails

• Switch to continuous daily dosing of sertraline 50-150 mg/day 4
• Consider escitalopram 10-20 mg/day as second-line SSRI option 4

Important Caveats

Monitoring Requirements

• Close monitoring for suicidal ideation is essential in the first 1-2 months and after dose changes, particularly in women under age 24 (boxed warning applies) 5
• Assess response within 1-2 treatment cycles; modify treatment if inadequate response 3

Common Pitfalls to Avoid

• Do not abruptly discontinue sertraline even with intermittent dosing, as it carries moderate risk for discontinuation syndrome (dizziness, fatigue, nausea, sensory disturbances) 5
• Avoid assuming all SSRIs are equivalent for PMDD—FDA approval and specific evidence matter for this indication 1
• Do not use escitalopram as first-line when sertraline is available and tolerated, given the regulatory and evidence advantage 1, 2

Shared SSRI Side Effects

Both medications cause similar adverse effects including nausea, dry mouth, diarrhea, headache, somnolence, insomnia, sexual dysfunction, and behavioral activation 5, 6