What is the recommended SSRI (Selective Serotonin Reuptake Inhibitor) for treating Premenstrual Syndrome (PMS)?

SSRI Treatment for Premenstrual Syndrome (PMS)

Sertraline is the recommended SSRI for treating premenstrual dysphoric disorder (PMDD) and severe PMS, with FDA approval specifically for this indication and proven efficacy at doses of 50-150 mg daily. 1

First-Line SSRI Recommendations

Sertraline should be the initial SSRI choice for PMS/PMDD based on its FDA approval and established efficacy profile. 1, 2 The medication can be administered either continuously (daily) or intermittently (luteal phase only), with both regimens demonstrating effectiveness. 3, 2

Dosing Strategies

• Continuous dosing: Sertraline 50-150 mg daily throughout the entire menstrual cycle is probably more effective than luteal-phase-only administration (SMD -0.69 vs -0.39). 2

• Luteal phase dosing: Sertraline 50-150 mg daily starting 14 days before expected menses and continuing until menstruation begins offers the advantage of reduced medication exposure and lower cost while maintaining efficacy. 1, 4, 5

• Clinical response occurs rapidly, typically within several days of treatment initiation, which supports the feasibility of intermittent dosing. 4

Alternative SSRIs

If sertraline is not tolerated or effective, consider these alternatives in order of preference:

• Fluoxetine 10-20 mg daily 6
• Paroxetine 12.5-25 mg daily 6
• Escitalopram 10-20 mg daily 6

All SSRIs demonstrate moderate effectiveness in reducing overall premenstrual symptoms (SMD -0.57), with particular benefit for psychological and behavioral symptoms. 2

Expected Benefits and Symptom Reduction

SSRIs provide clinically meaningful improvement in:

• Psychological symptoms (depressed mood, anxiety, irritability, mood swings) 2, 5
• Physical symptoms (bloating, breast tenderness, headache) 3
• Functional impairment and quality of life 3, 5

The magnitude of benefit is moderate, with standardized mean differences ranging from -0.39 to -0.69 depending on dosing strategy. 2

Common Adverse Effects and Management

Patients must be counseled about frequent side effects before initiating treatment. The most common adverse effects with their associated number needed to harm (NNTH) include:

• Nausea (NNTH = 7): Most common side effect, typically dose-dependent 3, 2
• Asthenia/decreased energy (NNTH = 9) 3
• Insomnia 2
• Sexual dysfunction or decreased libido (NNTH = 14) 3, 2
• Somnolence (NNTH = 13) 3
• Fatigue (NNTH = 14) 3
• Dizziness 2
• Sweating (NNTH = 14) 3

Adverse effects are dose-related, and withdrawal due to side effects is 2.55 times more likely with SSRIs compared to placebo. 3, 2

Critical Safety Considerations

• Avoid abrupt discontinuation of continuous daily SSRI therapy, as this may precipitate SSRI withdrawal syndrome. 7

• Exercise caution in adolescents and patients with comorbid depression, particularly those with suicidal ideation, though elevated suicide risk has not been found in non-depressed women treated for PMS. 7

• Avoid SSRIs in patients with bipolar disorder history due to risk of precipitating mania. 7

Treatment Selection Algorithm

1. Start with sertraline 50 mg daily (either continuous or luteal phase based on patient preference and symptom severity) 1, 6

2. If partial response after 2-3 menstrual cycles: Increase sertraline to 100-150 mg daily 1

3. If inadequate response or intolerable side effects: Switch to alternative SSRI (fluoxetine, paroxetine, or escitalopram) 6

4. Consider luteal-phase dosing for patients concerned about long-term medication use, cost, or who prefer intermittent treatment, as this minimizes adverse effects while maintaining efficacy 4, 5

5. Continuous dosing is preferred when symptoms are severe, when rapid control is needed, or when luteal-phase dosing proves insufficient 2

Important Clinical Pitfalls

Do not confuse PMS with PMDD - PMDD requires marked functional impairment and at least 5 symptoms including one core mood symptom (depressed mood, anxiety, affective lability, or irritability). 1 The evidence base primarily addresses PMDD, though SSRIs are used for severe PMS in clinical practice.

Prospective symptom charting for at least 2 menstrual cycles is essential to confirm the luteal-phase timing of symptoms and rule out other mood disorders that may worsen premenstrually. 1

Response assessment should occur after 2-3 menstrual cycles of treatment, as some women may require this duration to achieve optimal benefit. 2