What are the treatment options for a patient with premenstrual dysphoric disorder (PMDD)?

Treatment for Premenstrual Dysphoric Disorder (PMDD)

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacologic treatment for PMDD, with intermittent (luteal phase or symptom-onset) dosing being as effective as continuous daily dosing while minimizing medication exposure. 1, 2

First-Line Pharmacologic Treatment: SSRIs

SSRIs have been established as the primary treatment for PMDD based on their efficacy in reducing both psychological and physical symptoms 1, 2. The following SSRIs are recommended with specific dosing:

• Sertraline: 50-150 mg/day 3
• Fluoxetine: 10-20 mg/day 3
• Escitalopram: 10-20 mg/day 3
• Paroxetine: 12.5-25 mg/day 3

Dosing Strategies

Intermittent dosing should be prioritized over continuous daily dosing as it allows treatment for only 14 days per month and reduces overall medication exposure 2. Three intermittent approaches are effective:

• Luteal phase dosing: Start approximately 14 days before expected menses and continue through the first few days of menstruation 1, 2
• Symptom-onset dosing: Begin at symptom onset and continue until menses begins 4
• Continuous dosing: Daily administration throughout the menstrual cycle 1

Evidence shows that symptom-onset dosing with sertraline significantly improved depressive symptoms (IDS-C scores) and anger/irritability, with 67% of patients responding to treatment versus 52% with placebo 4. Importantly, abrupt cessation of intermittent SSRI treatment was not associated with discontinuation symptoms 4.

Second-Line Pharmacologic Options

Other Psychiatric Medications

When SSRIs are ineffective or not tolerated, consider:

• Venlafaxine (SNRI): Demonstrated efficacy for PMDD 1
• Duloxetine (SNRI): Shown to be effective 1
• Alprazolam (benzodiazepine): Recommended by the American College of Physicians, but use cautiously due to dependence risk 5, 1
• Buspirone: Has demonstrated utility for PMDD 1

Hormonal/Anovulatory Treatments

Drospirenone-containing oral contraceptives (3 mg drospirenone with 20 mcg ethinyl estradiol for 24 days, followed by 4 inactive days) are FDA-approved specifically for PMDD treatment in women who choose oral contraception 6, 3. This can be considered first-line or second-line treatment depending on patient preference for contraception 3.

Important contraindications for drospirenone include: renal impairment, adrenal insufficiency, high risk of thrombotic disease, undiagnosed abnormal uterine bleeding, breast cancer, and liver disease 6. Monitor serum potassium during the first treatment cycle in women on medications that may increase potassium levels, as drospirenone has anti-mineralocorticoid activity 6.

Non-Pharmacologic Interventions

First-Line Non-Pharmacologic Treatment

Regular aerobic exercise is recommended by the American College of Sports Medicine as a first-line treatment option for mild-to-moderate PMDD symptoms 5.

Cognitive Behavioral Therapy (CBT)

CBT demonstrates effectiveness in reducing functional impairment and multiple PMDD symptoms including depressed mood, hopelessness, anxiety, mood swings, irritability, insomnia, and interpersonal conflict 3. CBT can reduce the functional impact of PMDD and may become a first-line treatment as more evidence accumulates 3.

Adjunctive Treatments

Supplements with Evidence

• Calcium supplementation: The only supplement with consistent demonstrated therapeutic benefit for PMDD 1

Symptomatic Management

• NSAIDs: Recommended by the American Academy of Family Physicians for physical pain symptoms in PMDD 5

Treatment Algorithm

1. Initial assessment: Confirm PMDD diagnosis using DSM-5 criteria with prospective daily symptom charting for at least two menstrual cycles
2. Mild-to-moderate symptoms: Start with aerobic exercise and calcium supplementation 5, 1
3. Moderate-to-severe symptoms or inadequate response:
   • Initiate SSRI with intermittent (luteal phase or symptom-onset) dosing 1, 2, 4
   • If patient desires contraception, consider drospirenone-containing oral contraceptive 6, 3
4. Inadequate SSRI response: Switch to alternative SSRI or try continuous daily dosing 1
5. SSRI failure or intolerance: Consider venlafaxine, duloxetine, or buspirone 1
6. Adjunctive therapy at any stage: Add CBT to pharmacologic treatment 3

Critical Safety Considerations

Monitor for treatment-emergent suicidality, particularly in adolescents and young adults, as SSRIs carry black box warnings for this population 5.

Screen for contraindications before prescribing drospirenone, including checking renal function and assessing thrombotic risk factors 6. Women over 35 who smoke should not use drospirenone-containing contraceptives 6.

Avoid long-term benzodiazepine use due to dependence risk, despite alprazolam's demonstrated efficacy 5, 1.