What are the treatment options for premenstrual dysphoria?

Treatment of Premenstrual Dysphoric Disorder (PMDD)

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacologic treatment for PMDD, with sertraline, fluoxetine, and controlled-release paroxetine being FDA-approved for this indication and demonstrably effective in reducing both mood and physical symptoms. 1

First-Line Pharmacologic Treatment: SSRIs

Dosing Strategies

• Sertraline should be initiated at 50 mg daily for PMDD, administered either continuously throughout the menstrual cycle or limited to the luteal phase (last 2 weeks before menses), depending on symptom severity and patient preference 1

• For patients not responding to 50 mg daily, increase the dose in 50 mg increments up to a maximum of 150 mg/day for continuous dosing or 100 mg/day for luteal-phase dosing 1

• When using luteal-phase dosing at 100 mg/day, begin with a 50 mg/day titration step for the first 3 days of each luteal phase to minimize side effects 1

• Dose adjustments should not occur more frequently than once weekly due to sertraline's 24-hour elimination half-life 1

Evidence for Efficacy

• SSRIs demonstrated significant superiority over placebo in reducing PMDD symptoms as measured by the Daily Record of Severity of Problems (DRSP), Hamilton Depression Rating Scale, and Clinical Global Impressions scores in multiple controlled trials 1, 2, 3

• Unlike treatment of major depression, SSRIs for PMDD can be effective when used only during the luteal phase or even limited to symptom duration, not requiring continuous daily administration 2, 3

• The mean effective dose in clinical trials was approximately 100-150 mg/day for sertraline 1

Alternative SSRI Options

• Fluoxetine and controlled-release paroxetine are also FDA-approved for PMDD and represent equivalent first-line options if sertraline is not tolerated 3, 4

• All three FDA-approved SSRIs have demonstrated efficacy for both affective symptoms (depression, anxiety, irritability) and physical symptoms (bloating, breast tenderness, pain) 2, 5

Second-Line Pharmacologic Treatments

Other Antidepressants

• Venlafaxine (SNRI) is an effective alternative for patients who fail SSRI therapy or cannot tolerate SSRIs 3

• Duloxetine has also demonstrated benefit in PMDD treatment 3

Anxiolytics

• Alprazolam and buspirone can be used as second-line agents, particularly for patients with prominent anxiety symptoms 3, 4

• These should be reserved for patients who have not responded adequately to SSRIs 3

Hormonal/Anovulatory Treatments

Indications

• Ovulation suppression is an alternative approach when SSRIs and second-line psychotropic agents are ineffective 4

• Hormonal therapies primarily improve physical symptoms rather than mood symptoms, unlike SSRIs which address both 5

Considerations

• Combined oral contraceptives can be effective but primarily target physical symptoms (bloating, breast tenderness, pain) rather than affective symptoms 5, 4

• Side effects of hormonal therapies may limit their use compared to SSRIs 4

• Hormonal treatments should be considered second-line after SSRI failure due to the superior evidence base and tolerability profile of SSRIs 3, 4

Supportive and Adjunctive Treatments

Symptom-Specific Medications

• Spironolactone can be used for bloating and fluid retention symptoms 4

• NSAIDs are appropriate for pain-related symptoms (headache, joint/muscle pain, cramping) 4

Calcium Supplementation

• Calcium supplementation is the only supplement with consistent evidence of therapeutic benefit for PMDD 3

• This represents a reasonable adjunct to pharmacologic treatment 3

Lifestyle Modifications

• Exercise, stress reduction, and dietary modifications (reducing caffeine, alcohol, salt, and refined sugars) should be recommended for all patients as first-line non-pharmacologic interventions 6, 4

• These modifications may be sufficient for mild-to-moderate symptoms and should be implemented before or alongside pharmacotherapy 4

Cognitive Behavioral Therapy

• CBT can be effective as an adjunct to pharmacotherapy for improving coping strategies and reducing symptom severity 6, 4

• A holistic approach combining lifestyle modifications, pharmacotherapy, and CBT produces optimal outcomes for symptom reduction and quality of life improvement 6

Herbal and Alternative Treatments

• Chasteberry (Vitex agnus castus) and St. John's Wort (Hypericum perforatum) have some evidence supporting their use but results are inconsistent 2, 5

• These may serve as adjuncts but should not replace evidence-based pharmacotherapy for moderate-to-severe PMDD 2

• More controlled trials are needed before these can be routinely recommended, and potential drug interactions must be considered 4

Treatment Algorithm

1. Start with lifestyle modifications and exercise for all patients regardless of severity 6, 4

2. For mild symptoms: Continue lifestyle modifications, consider calcium supplementation and CBT 3, 6

3. For moderate-to-severe symptoms: Initiate SSRI therapy (sertraline 50 mg daily, either continuous or luteal-phase dosing) 1, 3

4. If inadequate response after 2-3 menstrual cycles: Increase SSRI dose up to maximum (150 mg/day continuous or 100 mg/day luteal-phase) 1

5. If SSRI failure or intolerance: Switch to alternative SSRI (fluoxetine or paroxetine CR) or try venlafaxine/duloxetine 3

6. If multiple antidepressant failures: Consider hormonal/anovulatory therapy (combined oral contraceptives) 4

7. Add symptom-specific treatments as needed: Spironolactone for bloating, NSAIDs for pain, anxiolytics for severe anxiety 4

Duration of Treatment

• The effectiveness of sertraline beyond 3 menstrual cycles has not been systematically evaluated in controlled trials 1

• Physicians should periodically re-evaluate the long-term need for continued treatment on an individual basis 1

• Many patients may require ongoing treatment given the chronic, recurrent nature of PMDD 2

Common Pitfalls to Avoid

• Do not assume amenorrhea equals infertility in patients with cycle irregularities; contraception counseling may still be needed 7

• Do not delay SSRI initiation in favor of prolonged trials of unproven supplements or herbal remedies for moderate-to-severe symptoms 3

• Do not use hormonal contraceptives as first-line treatment when mood symptoms predominate, as SSRIs have superior evidence for affective symptoms 5

• Do not increase SSRI doses more frequently than weekly intervals due to the drug's pharmacokinetics 1