What are the treatment options for premenstrual syndrome (PMS)?

Treatment of Premenstrual Syndrome

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for premenstrual syndrome, particularly for moderate-to-severe cases and premenstrual dysphoric disorder (PMDD), with proven efficacy for both emotional and physical symptoms. 1, 2

Initial Management Approach

Non-Pharmacological Interventions (First Step for Mild-Moderate PMS)

• Calcium supplementation (1200 mg daily) is the only supplement with consistent evidence for reducing emotional, behavioral, and physical premenstrual symptoms 3
• Lifestyle modifications including dietary changes, regular exercise, stress reduction, and adequate rest should be implemented before or alongside pharmacological treatment 4, 5
• Cognitive behavioral therapy has shown preliminary efficacy and can be considered as adjunctive treatment 3

Pharmacological Treatment Algorithm

First-Line: SSRIs

• SSRIs are established as the primary pharmacological treatment for PMS/PMDD, effective for both mood and physical symptoms 1, 2
• Can be dosed continuously throughout the cycle or intermittently during the luteal phase only 1
• Fluoxetine is FDA-approved for this indication and can be initiated at 20 mg daily 6
• Common pitfall: Failing to counsel patients about potential side effects including abnormal bleeding risk when combined with NSAIDs, and the need to monitor for mood changes, particularly suicidal ideation in the first weeks of treatment 6

Second-Line: Other Psychiatric Medications

• Venlafaxine and duloxetine (serotonin-norepinephrine reuptake inhibitors) have demonstrated efficacy 1
• Alprazolam used specifically during the premenstrual period can be effective for symptom relief 4
• Buspirone is another alternative option 1

Third-Line: Hormonal Approaches

• Combined oral contraceptives (COCs) are effective primarily for physical symptoms rather than mood symptoms 2
• COCs containing norgestimate have favorable side effect profiles 7
• Standard regimen: 21-24 hormone pills followed by 4-7 placebo pills, though extended/continuous regimens may provide better symptom control 7
• Important caveat: COCs carry approximately 3-4 times increased baseline risk of venous thromboembolism 7
• Ovulation suppression with gonadotropin-releasing hormone agonists is effective but limited by side effects including osteoporosis and cardiovascular risks from prolonged hypoestrogenism 3

Symptom-Specific Adjunctive Treatments

• For heavy or painful bleeding: NSAIDs (ibuprofen 400 mg every 4-6 hours) for 5-7 days during menstruation 8, 9
• Ibuprofen specifically indicated for dysmenorrhea at 400 mg every 4 hours as needed, starting with earliest onset of pain 9
• Mefenamic acid has shown efficacy in small studies for bleeding cessation 8

Treatment Selection Strategy

For patients with predominantly mood/emotional symptoms:

• Start with SSRI (continuous or luteal phase dosing) 1, 2
• Add calcium supplementation 1200 mg daily 3
• Consider cognitive behavioral therapy as adjunct 3

For patients with predominantly physical symptoms:

• Consider COCs as first-line if contraception also desired 2
• NSAIDs for pain and heavy bleeding during menstruation 8, 9
• Calcium supplementation 3

For patients with mixed symptoms:

• SSRI remains first-line due to efficacy for both symptom domains 1, 2
• Add NSAIDs for breakthrough physical symptoms 8

Critical Monitoring Points

• Diagnosis must be confirmed with prospective daily symptom charting (Daily Record of Severity of Problems) showing symptom-free period in follicular phase 2
• When initiating SSRIs, monitor closely for emergence of suicidal ideation, anxiety, agitation, or behavioral changes, particularly in first weeks 6
• Assess for drug interactions, especially when combining SSRIs with NSAIDs (increased bleeding risk) or other serotonergic agents (serotonin syndrome risk) 6
• If using COCs, screen for contraindications including thromboembolism risk factors 7

Common Pitfalls to Avoid

• Prescribing progesterone therapy—this has been proven ineffective despite historical use 4
• Starting hormonal treatment without confirming diagnosis through prospective symptom tracking 2
• Using COCs as monotherapy for severe mood symptoms when SSRIs would be more appropriate 2
• Failing to consider that many proposed treatments (evening primrose oil, magnesium, diuretics) lack robust evidence 4
• Not counseling about the 30-40% placebo response rate in PMS trials, which affects interpretation of treatment response 4