What are the treatment options for Premenstrual Dysphoric Disorder (PMDD) with normal hormone levels?

Treatment Options for Premenstrual Dysphoric Disorder (PMDD) with Normal Hormone Levels

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PMDD regardless of hormone levels, with continuous administration being more effective than luteal phase dosing. 1

First-Line Pharmacological Treatment

SSRIs

• SSRIs have demonstrated consistent efficacy for PMDD symptoms and are considered the gold standard treatment 2, 1

• Specific SSRIs with proven efficacy:

  • Sertraline (50-150 mg/day)
  • Fluoxetine (10-20 mg/day)
  • Escitalopram (10-20 mg/day)
  • Paroxetine (12.5-25 mg/day) 3

• Administration options:

  • Continuous daily dosing (more effective, SMD -0.69) 1
  • Luteal phase dosing (moderately effective, SMD -0.39) 1
  • Symptom-onset dosing (requires further research) 4

Combined Oral Contraceptives (COCs)

• Drospirenone-containing COCs are specifically FDA-approved for PMDD treatment
• Recommended formulation: Drospirenone 3 mg with ethinyl estradiol 20 μg in a 24/4 regimen 5
• Only appropriate for patients who:
  • Have already decided to use oral contraceptives for birth control, AND
  • Have been diagnosed with PMDD by a healthcare provider 5

Common Side Effects of First-Line Treatments

SSRIs

• Most common adverse effects (moderate-certainty evidence) 1:
  • Nausea (OR 3.30)
  • Asthenia/decreased energy (OR 3.28)
  • Somnolence/decreased concentration (OR 3.26)
  • Sexual dysfunction (OR 2.32)
  • Insomnia (OR 1.99)
  • Dizziness (OR 1.96)

Drospirenone-containing COCs

• Potential for increased potassium levels
• Contraindicated in patients with kidney, liver, or adrenal disease 5
• Should be used with caution in patients on:
  • NSAIDs (long-term use)
  • Potassium-sparing diuretics
  • ACE inhibitors
  • Angiotensin-II receptor antagonists 5

Second-Line and Alternative Treatments

Other Psychiatric Medications

• Venlafaxine (SNRI)
• Duloxetine (SNRI)
• Alprazolam (benzodiazepine)
• Buspirone 2

Supplements

• Calcium supplementation (most consistent evidence among supplements) 2
• Other supplements with limited evidence:
  • Vitamin B6
  • Magnesium
  • Omega-3 fatty acids

Non-Pharmacological Approaches

• Cognitive Behavioral Therapy (CBT)
  • Effective for reducing functional impairment, depressed mood, anxiety, irritability
  • May become first-line treatment with more evidence 3
• Regular exercise programs
• Stress management techniques

Treatment Algorithm

1. Initial Assessment:

   • Confirm PMDD diagnosis using DSM-5 criteria
   • Rule out other mood disorders
   • Verify normal hormone levels

2. First-Line Treatment:

   • For patients NOT requiring contraception: Start with an SSRI (continuous dosing preferred)
   • For patients requiring contraception: Consider drospirenone-containing COC

3. Inadequate Response to First-Line Treatment (after 2-3 cycles):

   • Switch to a different SSRI
   • Change from luteal phase to continuous dosing if using intermittent dosing
   • Add CBT to medication regimen

4. Second-Line Options (if multiple SSRIs fail):

   • Try SNRIs (venlafaxine or duloxetine)
   • Consider calcium supplementation as adjunctive therapy
   • For severe cases: Consider combination therapy with SSRI plus drospirenone-containing COC (if not contraindicated)

Important Clinical Considerations

• Approximately 40% of women with PMDD do not respond to SSRIs or COCs 6
• Treatment efficacy should be evaluated after at least 2-3 menstrual cycles
• Patients should be monitored for adverse effects, particularly with continuous SSRI dosing
• COCs should not be used solely for PMDD treatment unless contraception is also desired 5
• Patients with severe symptoms affecting quality of life may benefit from combination approaches

Pitfalls to Avoid

• Misdiagnosing PMDD as major depressive disorder or other mood disorders
• Using COCs as first-line treatment for PMDD when contraception is not needed
• Failing to distinguish between premenstrual syndrome (PMS) and the more severe PMDD
• Discontinuing treatment too early (before 2-3 cycles) when evaluating efficacy
• Overlooking non-pharmacological approaches that may enhance treatment response