What are the best treatment options for premenstrual dysphoric disorder (PMDD)?

Best Treatment Options for Premenstrual Dysphoric Disorder (PMDD)

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacologic treatment for PMDD, with FDA-approved options including fluoxetine, controlled-release paroxetine, and sertraline. 1, 2, 3, 4, 5

First-Line Pharmacologic Treatment: SSRIs

SSRIs demonstrate superior efficacy in reducing emotional, cognitive-behavioral, and physical symptoms of PMDD while improving psychosocial functioning. 3, 4, 5

Dosing Strategies for SSRIs

• Luteal phase dosing (starting 14 days before expected menses) is as effective as continuous daily dosing and may reduce costs, long-term side effects, and discontinuation syndrome risk. 4, 5
• Continuous daily dosing remains an alternative if luteal phase dosing proves inadequate. 5
• Symptom-onset dosing can be considered, though more research is needed to compare efficacy across dosing strategies. 5

FDA-Approved SSRIs for PMDD

• Fluoxetine 3, 4
• Controlled-release paroxetine 3
• Sertraline 3, 4

Second-Line Pharmacologic Options

If initial SSRI therapy fails:

• Switch to a different SSRI before abandoning this drug class entirely. 4
• Venlafaxine or duloxetine (serotonin-norepinephrine reuptake inhibitors) have demonstrated efficacy. 5
• Low-dose alprazolam administered intermittently during the luteal phase can be considered as second-line treatment. 4, 5
• Buspirone has shown benefit in some patients. 5

Hormonal Therapies

Oral Contraceptives

• Drospirenone-containing oral contraceptives (drospirenone 3 mg/ethinyl estradiol 0.02 mg) are FDA-approved for PMDD treatment, with proven efficacy in reducing PMDD symptoms compared to placebo. 1, 6
• Traditional oral contraceptives containing 19-nortestosterone-derived progestins have limited evidence and may paradoxically worsen PMS-like symptoms due to water retention and irritability. 6

Other Hormonal Options (Third-Line)

• GnRH agonists with add-back hormonal therapy are effective but reserved for refractory cases due to cost and serious side effect risks. 4, 6
• Danazol has demonstrated efficacy but is limited to short-term use due to adverse effects. 4, 6
• Estradiol patches/implants with progestin for endometrial protection show clinical evidence of benefit. 6

Non-Pharmacologic Interventions

First-Line for All Patients

• Lifestyle modifications and aerobic exercise are recommended as initial interventions for all women with PMDD, particularly those with mild-to-moderate symptoms. 2, 3, 6
• Cognitive behavioral therapy (CBT) and relaxation therapy have evidence supporting efficacy. 2, 6

Dietary Supplements with Evidence

• Calcium supplementation has demonstrated consistent therapeutic benefit and should be considered. 5, 6
• Magnesium and vitamin B6 have some supporting evidence. 6
• Omega-3 fatty acids may be considered as complementary therapy but lack strong PMDD-specific evidence and are not recommended as standalone treatment. 7

Limited or Unclear Evidence

• Complex carbohydrate drinks and L-tryptophan have preliminary evidence. 6
• Herbal supplements have produced unclear or conflicting results, requiring more controlled trials to establish safety, efficacy, and drug interaction potential. 3

Symptomatic Adjunctive Treatments

• Spironolactone (potassium-sparing diuretic) for bloating and water retention, though evidence is mixed. 3, 6
• NSAIDs for physical pain symptoms. 3

Treatment Algorithm

1. Start with lifestyle modifications, exercise, and calcium supplementation for all patients regardless of severity. 3, 5, 6
2. For moderate-to-severe PMDD requiring pharmacotherapy: Initiate an SSRI (fluoxetine, sertraline, or controlled-release paroxetine) using luteal phase dosing first. 3, 4, 5
3. If inadequate response: Switch to continuous SSRI dosing or try a different SSRI. 4, 5
4. If SSRIs fail or are contraindicated: Consider drospirenone-containing oral contraceptives, particularly if contraception is also desired. 1, 6
5. For refractory cases: Trial venlafaxine, duloxetine, or low-dose luteal phase alprazolam. 4, 5
6. Last resort for severe refractory PMDD: Short-term GnRH agonist therapy with add-back hormones. 4, 6

Critical Caveats

• Diagnosis requires prospective documentation of symptoms for at least two menstrual cycles using daily rating scales, with symptoms present 1-2 weeks premenstrually and relief by day 4 of menses. 6
• Functional impairment must be documented as part of diagnostic criteria. 2, 6
• Avoid traditional oral contraceptives with 19-nortestosterone-derived progestins as they may worsen symptoms. 6

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