What medications are used to treat premenstrual syndrome (PMS)?

Medications for Premenstrual Syndrome (PMS)

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for premenstrual syndrome due to their proven efficacy in reducing both physical and psychological symptoms. 1

First-Line Treatments

SSRIs

• FDA-approved SSRIs for PMS/PMDD:

  • Fluoxetine (Prozac) 2, 1
  • Paroxetine (controlled-release) 1
  • Sertraline 1
  • Citalopram 1
  • Escitalopram 1

• Dosing options:

  • Continuous daily dosing (more effective than luteal phase dosing) 1
  • Luteal phase dosing (starting 14 days before expected menses) 1

• Efficacy:

  • Moderate effect size for reducing overall PMS symptoms (SMD -0.57) 1
  • Continuous administration is more effective than luteal phase dosing (SMD -0.69 vs -0.39) 1

• Common side effects:

  • Nausea (most common)
  • Insomnia
  • Sexual dysfunction
  • Fatigue
  • Dizziness
  • Sweating
  • Dry mouth 1

Second-Line Treatments

Other Psychiatric Medications

• SNRIs:

  • Venlafaxine 3
  • Duloxetine 3

• Anxiolytics:

  • Alprazolam (for anxiety symptoms) 3, 4
  • Buspirone 3

Hormonal Treatments

• Combined hormonal contraceptives:
  • Primarily improve physical symptoms 5
  • Contraindicated in women with migraine with aura 6

Additional Treatment Options

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• Naproxen (can be used during perimenstrual period for pain and inflammation) 6, 4

Supplements

• Calcium supplementation:
  • Only supplement with consistent evidence of benefit 3

For Specific Symptoms

For Menstrual Migraines

• Long-acting NSAIDs (naproxen) starting 2 days before expected menstruation 6
• Triptans (frovatriptan or naratriptan) for 5 days starting 2 days before expected menstruation 6

For Problems with Ejaculation (if relevant)

• Daily SSRIs (paroxetine, sertraline, citalopram, fluoxetine) 6
• Clomipramine dosed on demand 6
  • Caution: Never combine clomipramine with MAOIs (including moclobemide) due to risk of serotonin syndrome 7

Treatment Algorithm

1. Start with lifestyle modifications:

   • Regular exercise
   • Stress reduction techniques
   • Dietary changes (reducing caffeine, salt, alcohol)

2. If symptoms persist, initiate pharmacotherapy:

   • For mild-moderate symptoms: Start with an SSRI (fluoxetine, sertraline, or citalopram)
   • Begin with continuous dosing for maximum efficacy
   • If side effects are problematic, consider switching to luteal phase dosing

3. If inadequate response to first SSRI:

   • Try a different SSRI
   • Consider an SNRI (venlafaxine or duloxetine)

4. For specific symptom management:

   • For physical pain: Add NSAIDs during symptomatic period
   • For anxiety: Consider adding an anxiolytic
   • For menstrual migraines: Add specific migraine prophylaxis

5. For severe, treatment-resistant cases:

   • Consider hormonal treatments
   • Evaluate for comorbid conditions

Important Considerations

• Monitor for side effects, particularly in the first weeks of treatment
• Assess response after 2-3 months of treatment 6
• Use headache/symptom calendars to track response 6
• Consider CYP2D6/CYP2C19 genetic testing in cases of treatment failure or unusual side effects 6
• Avoid combining serotonergic medications due to risk of serotonin syndrome 7

The evidence strongly supports that SSRIs are the most effective medication class for PMS, with continuous dosing providing better symptom control than luteal phase dosing.