What is the recommended treatment for a patient with Premenstrual Dysphoric Disorder (PMDD) who does not require contraception?

Treatment of PMDD Without Need for Contraception

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacologic treatment for PMDD in patients not requiring contraception, with sertraline, fluoxetine, escitalopram, or paroxetine administered either continuously or during the luteal phase only. 1, 2, 3

First-Line Pharmacologic Treatment: SSRIs

SSRIs should be initiated as primary therapy for patients with PMDD who do not need contraception, as they directly target the serotonergic mechanisms implicated in PMDD pathophysiology. 2, 3, 4

Specific SSRI Regimens

The following SSRIs have established efficacy for PMDD treatment:

• Sertraline 50-150 mg/day - FDA-approved for PMDD with demonstrated efficacy in both continuous daily dosing and luteal phase-only administration 1, 2
• Fluoxetine 10-20 mg/day 2, 3
• Escitalopram 10-20 mg/day 2
• Paroxetine 12.5-25 mg/day 2

Dosing Strategy: Continuous vs. Luteal Phase

Either continuous or luteal phase dosing can be effective, though the choice should consider patient preference, cost, and side effect profile:

• Luteal phase dosing (starting 14 days before menses and discontinuing at onset) reduces long-term side effects, cost, and risk of discontinuation syndrome 4, 5
• Continuous daily dosing throughout the menstrual cycle is also effective and may be preferred for patients with continuous symptoms 1, 5
• Symptom-onset dosing (starting when symptoms begin) has shown efficacy and may further reduce medication exposure 3, 5

Expected Response and Treatment Failure

Approximately 60% of patients respond to SSRI therapy after accounting for placebo effect, meaning 40% will not achieve adequate response. 6 If a patient fails to respond to one SSRI after an adequate trial (typically 2-3 menstrual cycles), switching to another SSRI should be attempted before considering alternative treatments. 5

Second-Line Pharmacologic Options

If SSRIs are ineffective or not tolerated, consider the following alternatives:

Other Antidepressants

• Venlafaxine (serotonin-norepinephrine reuptake inhibitor) has demonstrated efficacy for PMDD 3
• Duloxetine may be considered as an alternative serotonergic agent 3

Anxiolytics

• Alprazolam administered intermittently during the luteal phase may be used as second-line treatment, though caution is warranted due to dependence risk 7, 3, 5
• Buspirone has shown benefit in some studies 3

Non-Pharmacologic Interventions

Regular aerobic exercise should be recommended as a first-line treatment option for mild-to-moderate PMDD symptoms and can be used adjunctively with pharmacotherapy. 7

Cognitive Behavioral Therapy (CBT)

CBT has demonstrated effectiveness in reducing functional impairment, depressed mood, anxiety, mood swings, irritability, and symptom severity associated with PMDD. 2 CBT can be particularly valuable for patients who:

• Prefer non-pharmacologic approaches
• Have contraindications to medications
• Experience inadequate response to SSRIs alone
• Require additional support for functional impairment 2

Nutritional Supplementation

• Calcium supplementation has demonstrated consistent therapeutic benefit and should be considered as an adjunctive treatment 3
• NSAIDs may be used for physical pain symptoms during the luteal phase 7

Treatment Algorithm

1. Initial assessment: Confirm PMDD diagnosis using prospective daily symptom charting for at least 2 menstrual cycles
2. First-line: Initiate SSRI (sertraline 50-150 mg/day, fluoxetine 10-20 mg/day, escitalopram 10-20 mg/day, or paroxetine 12.5-25 mg/day) with either luteal phase or continuous dosing 1, 2
3. Adjunctive measures: Add regular aerobic exercise and calcium supplementation 7, 3
4. Reassess after 2-3 cycles: If inadequate response, switch to alternative SSRI 5
5. If second SSRI fails: Consider venlafaxine, duloxetine, or luteal phase alprazolam 3, 5
6. Consider CBT: At any stage, particularly for patients with significant functional impairment or preference for psychotherapy 2

Critical Monitoring Considerations

Monitor for treatment-emergent suicidality, particularly in adolescents and young adults, as SSRIs carry black box warnings for this population. 7 Regular follow-up during the first 2-3 months of treatment is essential to assess response and tolerability.

Important Caveats

• Avoid combined oral contraceptives in this population since contraception is not needed; they would add unnecessary hormonal exposure without addressing the primary indication 2
• Symptom improvement typically occurs within 1-2 menstrual cycles with SSRIs, which is faster than the response seen in major depressive disorder 4, 5
• Intermittent dosing strategies are unique to PMDD and distinguish its treatment from other mood disorders, reflecting the cyclical nature of the condition 4, 5