What is the treatment for premenstrual syndrome?

Treatment of Premenstrual Syndrome

For premenstrual syndrome (PMS), first-line treatment consists of lifestyle modifications combined with calcium carbonate 1200 mg daily, with selective serotonin reuptake inhibitors (SSRIs) reserved for moderate-to-severe symptoms or when calcium fails. 1

Initial Non-Pharmacological Management

All women with PMS should begin with lifestyle modifications regardless of symptom severity, as these interventions carry no risk and provide overall health benefits even though evidence quality is limited. 2, 1

• Dietary modifications: Increase complex carbohydrates, reduce caffeine and alcohol intake, and maintain regular meal timing to stabilize blood glucose 3, 2
• Regular aerobic exercise: 30 minutes most days of the week, though evidence is inconclusive, the risk-benefit ratio strongly favors this intervention 2, 1
• Stress reduction techniques: Cognitive behavioral therapy, relaxation exercises, and adequate sleep (7-9 hours nightly) 3, 2

First-Line Pharmacological Treatment

Calcium Supplementation

Calcium carbonate 1200 mg daily should be recommended as first-line pharmacological therapy for mild-to-moderate PMS, based on level I evidence demonstrating significant symptom reduction. 1 This represents the strongest evidence for any non-SSRI intervention and should be initiated before considering other pharmacological options.

SSRIs for Moderate-to-Severe Symptoms

SSRIs are the most effective pharmacological treatment for PMS and PMDD and should be considered first-line therapy for women with severe affective symptoms or those who fail calcium supplementation. 2, 1, 4

FDA-approved SSRIs for PMDD include:

• Fluoxetine (20-60 mg daily) 2, 4
• Sertraline (50-150 mg daily) 2, 4
• Paroxetine controlled-release (12.5-25 mg daily) 2, 4

Dosing strategies:

• Continuous daily dosing is more effective than luteal-phase-only administration (SMD -0.69 vs -0.39, P=0.03 for subgroup difference) 4
• Luteal phase dosing (starting 14 days before expected menses) can be used if patients prefer intermittent treatment or to minimize side effects 2, 4
• Symptom-onset dosing (starting when symptoms appear) may be effective but requires additional research 5

Second-Line Pharmacological Options

If SSRIs are ineffective or not tolerated after 2-3 menstrual cycles:

Alternative antidepressants:

• Venlafaxine 50-200 mg daily (serotonin-norepinephrine reuptake inhibitor) 5
• Duloxetine 60-120 mg daily 5

Anxiolytics for predominant anxiety symptoms:

• Alprazolam 0.25 mg three times daily during luteal phase only (avoid continuous use due to dependence risk) 2, 5
• Buspirone 10 mg twice daily 5

Hormonal suppression of ovulation (when SSRIs and other psychotropic agents fail):

• Combined oral contraceptives containing drospirenone (which has anti-mineralocorticoid properties) 2, 5
• GnRH agonists with add-back estrogen-progestin therapy (reserved for refractory cases due to side effects and cost) 5

Symptom-Specific Adjunctive Treatments

For breast tenderness and bloating:

• Spironolactone 25-100 mg daily during luteal phase (days 12-28 of cycle) 2, 1

For physical pain symptoms (cramping, headache, body aches):

• NSAIDs (ibuprofen 400-800 mg every 6-8 hours or naproxen 220-550 mg every 12 hours) taken during symptomatic days 2, 1

Treatments with Insufficient Evidence

The following commonly used therapies lack conclusive evidence and should not be recommended as primary treatment:

• Vitamin B6 (pyridoxine): conflicting results, no consistent benefit demonstrated 2, 1
• Evening primrose oil: inconclusive evidence 1
• Magnesium supplementation: inconclusive evidence 1
• Herbal supplements (chasteberry, St. John's wort): unclear or conflicting results with potential drug interactions 2

Progesterone and bromocriptine are ineffective and should not be used despite historical popularity. 1

Common Adverse Effects of SSRIs

Patients must be counseled about expected side effects before initiating SSRI therapy:

• Nausea (most common, OR 3.30): occurs in approximately 15-20% vs 5% with placebo 4
• Sexual dysfunction or decreased libido (OR 2.32) 4
• Insomnia (OR 1.99) 4
• Fatigue or sedation (OR 1.52) 4
• Somnolence and decreased concentration (OR 3.26) 4
• Dizziness (OR 1.96) 4
• Dry mouth (OR 2.70) 4
• Diarrhea (OR 2.06) 4

Most side effects are mild-to-moderate and often improve after 2-3 weeks of treatment. 2, 4

Treatment Algorithm

1. All patients: Lifestyle modifications + calcium carbonate 1200 mg daily 1
2. If inadequate response after 2-3 cycles: Add SSRI (fluoxetine, sertraline, or paroxetine CR) using continuous dosing 2, 1, 4
3. If SSRI ineffective or not tolerated: Switch to alternative SSRI or try venlafaxine/duloxetine 5
4. If antidepressants fail: Consider hormonal suppression with drospirenone-containing oral contraceptives 2, 5
5. Add symptom-specific agents as needed: Spironolactone for bloating, NSAIDs for pain 2, 1

Critical Diagnostic Requirement

Diagnosis must be confirmed with prospective daily symptom charting for at least two consecutive menstrual cycles, documenting symptoms during the luteal phase (14 days before menses) with a symptom-free interval of at least 7 days in the follicular phase. 3, 2 Treatment should not be initiated based on retrospective recall alone, as this leads to overdiagnosis.

Important Caveats

• 68% of SSRI trials were pharmaceutical-industry funded, which may introduce bias toward positive results; interpret efficacy data cautiously 4
• Approximately 18% of women do not respond to SSRIs, requiring alternative approaches 6
• Treatment selection should account for: desire for contraception (favoring hormonal methods), predominant symptom type (affective vs physical), and patient preference for continuous vs intermittent therapy 2
• Avoid prescribing treatment without confirmed prospective diagnosis, as many conditions mimic PMS (depression, anxiety disorders, thyroid dysfunction) 3, 2