What is the most effective Selective Serotonin Reuptake Inhibitor (SSRI) for a patient with Premenstrual Dysphoric Disorder (PMDD)?

Best SSRI for PMDD

Sertraline and fluoxetine are the preferred SSRIs for PMDD, with sertraline having the most robust FDA approval data for both continuous and luteal-phase dosing regimens. 1

First-Line SSRI Selection

Sertraline should be considered the first-line SSRI for PMDD based on:

• FDA approval with extensive clinical trial data demonstrating efficacy in two large placebo-controlled trials (n=251 and n=281) with both continuous daily dosing (50-150 mg/day, mean 102 mg/day) and luteal-phase-only dosing (50-100 mg/day, mean 74 mg/day) 1
• Both dosing strategies showed significant improvement on the Daily Record of Severity of Problems (DRSP) total score, Hamilton Depression Rating Scale, and Clinical Global Impression scores 1
• Sertraline transfers to breast milk in lower concentrations than other antidepressants, making it preferable for breastfeeding women 2

Fluoxetine is an equally strong alternative, as it was the first SSRI approved by the FDA specifically for PMDD and has the largest body of evidence 2, 3:

• Effective at 20 mg daily with both continuous and luteal-phase dosing 3
• Also effective at lower doses (10 mg) for luteal-phase administration 3
• Unique dosing option of 90 mg administered 2 weeks and 1 week prior to menses 3
• Generally well-tolerated with no reported discontinuation effects with intermittent dosing 3

Paroxetine is FDA-approved for PMDD but should be considered third-line 2:

• Higher rates of sexual dysfunction compared to fluoxetine, fluvoxamine, nefazodone, or sertraline 2
• Response rates of 50-93.8% in treatment studies 4
• Less favorable for breastfeeding compared to sertraline 2

Dosing Strategy Selection

Luteal-phase dosing should be attempted first before continuous dosing 5:

• Intermittent SSRI therapy allows medication use for only 14 days each month 5
• Reduces overall drug exposure and potentially minimizes long-term adverse effects 5
• Both continuous and luteal-phase administration are effective, though continuous dosing may have slightly superior efficacy (SMD -0.69 vs -0.39, P=0.03) 6

For sertraline luteal-phase dosing:

• Start at 50 mg daily beginning 2 weeks before expected menses 1
• Can titrate to 100 mg/day if needed (give 50 mg for first 3 days, then 100 mg remainder of cycle) 1
• Discontinue at onset of menses 1

For continuous dosing if luteal-phase fails:

• Sertraline 50-150 mg daily throughout entire menstrual cycle 1
• Fluoxetine 20 mg daily 3

Expected Efficacy and Timeline

SSRIs demonstrate rapid onset of action in PMDD, unlike depression treatment 7:

• Symptom improvement occurs within the first treatment cycle 7
• This rapid response suggests a different mechanism of action than antidepressant effects, possibly involving neurosteroids 7
• Overall reduction in premenstrual symptoms: SMD -0.57 (95% CI -0.72 to -0.42) 6

Critical Safety Considerations

Avoid abrupt discontinuation of continuous daily SSRI therapy, as this may precipitate SSRI withdrawal syndrome 8

Exercise caution in specific populations:

• 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) 8
• Patients with bipolar disorder history due to risk of precipitating mania 8

Common Adverse Effects

Patients should be counseled about expected adverse effects (all moderate-certainty evidence) 6:

• Most common: Nausea (OR 3.30), asthenia/decreased energy (OR 3.28), somnolence/decreased concentration (OR 3.26)
• Sexual dysfunction: OR 2.32 - can be problematic long-term but not systematically evaluated in PMDD populations 6, 7
• Other frequent effects: Insomnia (OR 1.99), dizziness (OR 1.96), dry mouth (OR 2.70), diarrhea (OR 2.06) 6
• Most adverse effects are mild and transient 7

Clinical Pitfalls to Avoid

Do not use fluvoxamine - mixed efficacy results reported in PMDD trials 7

Ensure proper diagnosis: PMDD requires prospective symptom charting for at least two menstrual cycles to confirm luteal-phase-only symptoms that remit with menses 1

Rule out other cyclical mood disorders that may be exacerbated by antidepressant treatment before initiating SSRIs 1