Hormone-Free Treatment for PMDD
SSRIs are the first-line hormone-free treatment for PMDD, with sertraline (50-150 mg/day) being FDA-approved and demonstrating significant efficacy in reducing both emotional and physical symptoms. 1
Primary Pharmacologic Treatment: SSRIs
Selective serotonin reuptake inhibitors (SSRIs) are established as first-line therapy for PMDD and can be administered using flexible dosing strategies 2, 3:
FDA-Approved SSRI Dosing Options
Sertraline is FDA-approved for PMDD with two validated regimens 1:
- Continuous daily dosing: 50-150 mg/day throughout the entire menstrual cycle (mean effective dose: 102 mg/day)
- Luteal phase dosing: 50-100 mg/day for the 2 weeks prior to menses onset, then discontinued
Both dosing strategies demonstrated significant superiority over placebo on validated outcome measures including the Daily Record of Severity of Problems (DRSP), Hamilton Depression Rating Scale, and Clinical Global Impression scores 1
Alternative SSRI Options
Other SSRIs with demonstrated efficacy for PMDD include 2, 3:
- Fluoxetine: 10-20 mg/day (effective in both continuous and luteal phase dosing) 4
- Escitalopram: 10-20 mg/day
- Paroxetine: 12.5-25 mg/day
A critical advantage of SSRIs for PMDD is that they work rapidly—often within days—unlike their use in depression, and can be effective with intermittent (luteal phase only) dosing without discontinuation effects 5, 4.
Other Pharmacologic Options
SNRI Antidepressants
- Venlafaxine and duloxetine have demonstrated efficacy for PMDD as alternative serotonergic agents 2
- These may be considered if SSRIs are not tolerated or ineffective
Anxiolytics
- Alprazolam and buspirone have shown benefit for PMDD symptoms 2
- These are typically reserved for patients who fail SSRI therapy
Non-Pharmacologic Approaches
Cognitive Behavioral Therapy (CBT)
CBT demonstrates clear effectiveness in reducing functional impairment, depressed mood, anxiety, mood swings, irritability, and conflict associated with PMDD 3:
- Reduces the impact of premenstrual symptoms on daily life
- Decreases symptom severity and handicap
- May be considered first-line treatment alongside SSRIs, though more comparative research is needed 3
Calcium Supplementation
Calcium supplementation is the only supplement with consistent therapeutic benefit for PMDD 2, 5:
- This represents the most evidence-based over-the-counter option
- Dosing typically involves 1200 mg daily of elemental calcium
Other Complementary Options
- Omega-3 fatty acids may be considered as complementary therapy, though evidence specifically for PMDD is limited 6
- Agnus castus (chasteberry) and Hypericum perforatum (St. John's wort) have some supporting data but less robust evidence 5
- These should be considered adjunctive rather than primary treatments
Treatment Algorithm
Start with an SSRI (sertraline 50-150 mg/day is FDA-approved) using either continuous or luteal phase dosing based on patient preference 1, 2
Add or combine with CBT for comprehensive symptom management, particularly for functional impairment 3
Consider calcium supplementation (1200 mg/day) as an adjunct or for patients preferring non-prescription options 2, 5
If SSRI fails: Switch to alternative SSRI, try SNRI (venlafaxine/duloxetine), or consider anxiolytics 2
Critical Caveats
Approximately 40% of women with PMDD do not respond adequately to SSRIs even after accounting for placebo effects 7. This substantial non-response rate underscores the importance of:
- Setting realistic expectations with patients
- Having alternative treatment strategies ready
- Considering combination approaches early rather than waiting for monotherapy failure
- Recognizing that luteal phase dosing may improve tolerability while maintaining efficacy 1, 4
The rapid onset of action with SSRIs in PMDD (days rather than weeks) differs markedly from depression treatment, making symptom-onset dosing a viable strategy 5.