Is famotidine (Histamine-2 (H2) blocker) effective for treating Premenstrual Dysphoric Disorder (PMDD)?

Famotidine for PMDD

Famotidine is not an effective treatment for PMDD and should not be used for this indication. There is no evidence supporting the use of H2 blockers like famotidine for premenstrual dysphoric disorder.

Evidence-Based First-Line Treatments

Selective serotonin reuptake inhibitors (SSRIs) are the established first-line pharmacologic treatment for PMDD 1, 2, 3, 4. The following SSRIs have demonstrated efficacy:

• Sertraline 50-150 mg/day 4
• Fluoxetine 10-20 mg/day 4
• Escitalopram 10-20 mg/day 4
• Paroxetine 12.5-25 mg/day (controlled-release formulation is FDA-approved for PMDD) 2, 4

Dosing Strategies for SSRIs

Unlike depression treatment, SSRIs for PMDD can be administered in multiple effective regimens 1, 3:

• Continuous daily dosing throughout the month 1, 3
• Luteal phase dosing (starting approximately 14 days before expected menses) 1, 3
• Symptom-onset dosing (starting when symptoms begin) 3

The luteal phase and symptom-onset approaches are unique to PMDD treatment and allow for reduced medication exposure 3.

Second-Line Pharmacologic Options

Hormonal Contraceptives

Drospirenone-containing oral contraceptives (3 mg drospirenone + 20 mcg ethinyl estradiol in a 24+4 day regimen) are FDA-approved for PMDD treatment 5. This represents the only hormonal contraceptive specifically approved for this indication 5.

• These agents work through ovulation suppression 2, 3
• Consider as first-line if contraception is also desired 2
• May be used as second-line when SSRIs are ineffective or contraindicated 4

Other Antidepressants

If SSRIs are ineffective or not tolerated 1:

• Venlafaxine (SNRI) has demonstrated efficacy 1
• Duloxetine (SNRI) has shown benefit 1

Anxiolytics

• Alprazolam can be used for symptom relief 1
• Buspirone has demonstrated utility 1

Supportive Treatments

Calcium supplementation (1200 mg/day) is the only supplement with consistent evidence of therapeutic benefit 1, 3. This can be recommended as an adjunct to primary pharmacologic treatment 3.

Treatment Algorithm

1. Confirm diagnosis with prospective daily symptom charting for at least two menstrual cycles showing luteal phase symptoms with follicular phase remission 3

2. Initiate SSRI therapy as first-line treatment 1, 2, 3, 4:

   • Start with sertraline, fluoxetine, escitalopram, or paroxetine
   • Choose between continuous or luteal-phase dosing based on patient preference and symptom severity
   • Assess response after 2-3 menstrual cycles

3. If inadequate SSRI response:

   • Try alternative SSRI or switch to SNRI (venlafaxine or duloxetine) 1
   • Consider drospirenone-containing oral contraceptive, especially if contraception desired 4, 5

4. Add adjunctive treatments as needed:

   • Calcium supplementation 1200 mg/day 1, 3
   • Anxiolytics for breakthrough anxiety symptoms 1

5. Consider cognitive behavioral therapy (CBT) as adjunct or alternative to medication 3, 4:

   • CBT reduces functional impairment, mood symptoms, and symptom severity 4
   • Can be first-line for patients preferring non-pharmacologic approaches 4

Critical Pitfalls to Avoid

• Do not use famotidine or other H2 blockers - there is no mechanistic rationale or evidence for efficacy in PMDD
• Do not confuse premenstrual syndrome (PMS) with PMDD - PMDD requires specific diagnostic criteria including marked functional impairment 3, 4
• Avoid opioids - no role in PMDD management and risk of dependence
• Do not dismiss patient symptoms - PMDD significantly impairs personal, social, family, and professional functioning 4