What are the treatment options for Premenstrual Syndrome (PMS)?

Treatment of Premenstrual Syndrome (PMS)

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacologic treatment for PMS and premenstrual dysphoric disorder (PMDD), with fluoxetine, sertraline, and controlled-release paroxetine being FDA-approved for this indication. 1, 2, 3

Initial Management Approach

Non-Pharmacologic Interventions (First-Line for All Patients)

• Lifestyle modifications should be implemented first for all women with PMS, particularly those with mild-to-moderate symptoms, as these may be sufficient without medication. 4
• Aerobic exercise has demonstrated efficacy in randomized controlled trials and should be recommended. 5
• Calcium supplementation is the only supplement with consistent therapeutic benefit across studies and should be considered. 2
• Cognitive behavioral therapy and stress management techniques have shown effectiveness in controlled trials. 6, 5

When to Initiate Pharmacologic Treatment

• Moderate-to-severe symptoms causing functional impairment in personal relationships or occupational activities warrant pharmacologic intervention. 3
• Symptoms must be documented prospectively for at least two cycles using a daily rating form (Daily Record of Severity of Problems) before initiating treatment. 3, 5

Pharmacologic Treatment Algorithm

First-Line: SSRIs

SSRIs are proven safe and effective for both physical and mood symptoms of PMS/PMDD. 2, 3, 4

FDA-approved SSRIs for PMDD:

• Fluoxetine (Prozac/Sarafem): 20 mg daily or 5-20 mg/day 1, 2
• Sertraline (Zoloft): 25-200 mg daily 2
• Controlled-release paroxetine (Paxil): 10-40 mg daily 2, 4

Dosing strategies (both effective, choice based on patient preference):

• Continuous daily dosing throughout the menstrual cycle 2, 4
• Luteal phase dosing (starting 14 days before expected menses) 2, 4
• Symptom-onset dosing is also an option, though more research is needed comparing efficacy between regimens 2

Second-Line: Other Psychotropic Medications

If SSRIs are ineffective or not tolerated:

• Venlafaxine (serotonin-norepinephrine reuptake inhibitor) has demonstrated efficacy 2
• Duloxetine has shown benefit 2
• Alprazolam (anxiolytic) used premenstrually can be effective, particularly for anxiety symptoms 2, 6
• Buspirone has demonstrated utility 2

Third-Line: Hormonal Suppression of Ovulation

Consider hormonal therapy when SSRIs and second-line psychotropic agents fail. 2, 4

• Combined oral contraceptives (COCs) primarily improve physical symptoms rather than mood symptoms 3, 5
• Traditional COCs containing 19-nortestosterone-derived progestins have limited evidence for efficacy and may worsen PMS-like symptoms 5
• Drospirenone-containing oral contraceptives (a spironolactone analog) show preliminary evidence for reducing water retention and other symptoms 5
• GnRH analogs with add-back hormonal therapy have good clinical evidence but are limited by cost and side effects 5
• Estradiol patches/implants with progestin for endometrial protection demonstrate efficacy 5

Adjunctive Symptomatic Treatment

• Spironolactone (potassium-sparing diuretic) for bloating and water retention 4, 5
• NSAIDs for pain symptoms 4
• Magnesium and vitamin B6 supplementation have some supporting evidence 5

Important Clinical Considerations

Common Pitfalls to Avoid

• Do not use progesterone therapy—it has been proven ineffective in controlled trials. 6
• Avoid relying solely on patient recall; require prospective symptom documentation for at least two cycles before diagnosis and treatment. 3, 5
• Traditional COCs may worsen symptoms in some patients due to progestin effects; monitor closely. 5

Treatment Selection Strategy

1. For predominantly mood symptoms: Start with SSRIs (continuous or luteal phase dosing) 2, 3
2. For predominantly physical symptoms: Consider COCs (particularly drospirenone-containing) or symptomatic treatment with spironolactone/NSAIDs 3, 4
3. For patients requiring contraception: Drospirenone-containing COCs may address both needs 5
4. For patients with contraindications to SSRIs: Consider anxiolytics (alprazolam) or other psychotropic agents 2, 6

Monitoring and Adjustment

• Reassess symptom severity using prospective daily ratings after 2-3 menstrual cycles of treatment. 3, 5
• If inadequate response to first SSRI, trial a different SSRI before moving to second-line agents. 2, 4
• Consider switching from continuous to luteal-phase dosing (or vice versa) if partial response occurs. 2