What is the recommended treatment for premenstrual dysphoric disorder (PMDD)?

Treatment of Premenstrual Dysphoric Disorder (PMDD)

Selective serotonin reuptake inhibitors (SSRIs) are the established first-line treatment for PMDD, with the unique advantage that they can be dosed either continuously throughout the menstrual cycle or intermittently during the luteal phase only. 1, 2, 3

First-Line Pharmacologic Treatment: SSRIs

SSRIs have been proven safe and effective for PMDD treatment and are FDA-approved for this indication 4, 5. The following agents and dosing regimens are recommended:

FDA-Approved SSRIs for PMDD:

• Fluoxetine: 10-20 mg/day 2, 6
• Sertraline: 50-150 mg/day 2, 5
• Paroxetine (controlled-release): 12.5-25 mg/day 2, 5
• Escitalopram: 10-20 mg/day 2

Dosing Strategies

Intermittent (luteal phase) dosing is as effective as continuous daily dosing for PMDD, unlike treatment of major depressive disorder. 3, 6 This represents a critical distinction in PMDD management:

• Luteal phase dosing: Start at ovulation (approximately day 14) and continue until menses 3, 6
• Symptom-onset dosing: Begin when symptoms appear and continue through menses 1
• Continuous daily dosing: Throughout the entire menstrual cycle 6, 5

Fluoxetine has demonstrated efficacy even with dosing limited to 2 and 1 week prior to menses at 90 mg 6. Discontinuation effects have not been reported with intermittent dosing regimens 6.

Second-Line Pharmacologic Options

Hormonal Suppression of Ovulation

Drospirenone-containing oral contraceptives (3 mg drospirenone + 20 mcg ethinyl estradiol, 24 days active/4 days inactive) are effective for PMDD and can be considered first or second-line treatment. 2 This approach targets ovulation suppression, addressing the hormonal fluctuations that trigger PMDD symptoms 3.

Other Psychotropic Medications

When SSRIs are ineffective or not tolerated, consider 1:

• Venlafaxine (SNRI)
• Duloxetine (SNRI)
• Alprazolam (benzodiazepine - use cautiously due to dependence risk)
• Buspirone (anxiolytic)

Supportive Symptomatic Treatments

For targeted symptom relief 5:

• Spironolactone: For bloating and fluid retention
• NSAIDs: For physical pain symptoms
• Anxiolytics: For acute anxiety symptoms (short-term use)

Non-Pharmacologic Interventions

Cognitive Behavioral Therapy (CBT)

CBT demonstrates clear effectiveness in reducing functional impairment, depressed mood, anxiety, mood swings, irritability, and conflict associated with PMDD. 2 CBT specifically reduces:

• Functional impairment in daily life 2
• Depressed mood and hopelessness 2
• Anxiety and mood swings 2
• Sensitivity and irritability 2
• Insomnia 2
• Interpersonal conflict 2

CBT may become a first-line treatment option as more evidence accumulates 2.

Lifestyle Modifications

Despite limited specific evidence, lifestyle modifications are recommended as first-line for all women with PMDD and may suffice for mild-to-moderate symptoms 5:

• Regular aerobic exercise 5
• Stress reduction techniques 5
• Sleep hygiene optimization 5

Supplements with Evidence

Calcium supplementation (1200 mg/day) is the only supplement with consistent demonstrated therapeutic benefit for PMDD. 1, 5

Other supplements with limited or conflicting evidence 1, 5:

• Vitex agnus castus (chasteberry) - may be useful adjunct 3
• Hypericum perforatum (St. John's wort) - may be useful adjunct 3
• Omega-3 fatty acids - unclear efficacy 5
• Vitamin supplementation - unclear or conflicting results 5

Treatment Algorithm

1. Confirm diagnosis: Use prospective daily symptom charting for at least 2 menstrual cycles to document luteal phase symptoms with follicular phase remission 1, 3

2. Mild-to-moderate symptoms: Begin with lifestyle modifications, exercise, and calcium supplementation 5

3. Moderate-to-severe symptoms requiring pharmacotherapy:

   • First choice: SSRI (fluoxetine 10-20 mg, sertraline 50-150 mg, escitalopram 10-20 mg, or paroxetine CR 12.5-25 mg) 2
   • Dosing option: Start with luteal phase dosing for convenience and reduced side effects; switch to continuous if inadequate response 3, 6

4. If SSRI inadequate or not tolerated:

   • Switch to alternative SSRI or SNRI (venlafaxine, duloxetine) 1
   • Consider drospirenone-containing oral contraceptive if contraception also desired 2

5. Adjunctive treatments: Add CBT, symptomatic treatments (NSAIDs, spironolactone), or calcium supplementation as needed 2, 5

6. Refractory cases: Consider combination therapy with SSRI plus hormonal suppression, or referral to specialist 1, 3

Critical Pitfalls to Avoid

• Do not confuse PMDD with premenstrual syndrome (PMS): PMDD requires marked functional impairment and specific DSM-5 criteria 1, 3
• Do not assume daily dosing is necessary: Luteal phase SSRI dosing is equally effective and may improve tolerability 3, 6
• Monitor for treatment-emergent suicidality: SSRIs carry black box warnings for suicidality in adolescents and young adults 4
• Distinguish PMDD from premenstrual exacerbation of underlying mood disorder: The latter requires different treatment approach 3
• Avoid herbal supplements with unclear drug interactions: Many have conflicting evidence and potential for interactions 5