What is the drug of choice for Premenstrual Syndrome (PMS)?

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Last updated: June 16, 2025View editorial policy

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From the Guidelines

The drug of choice for Premenstrual Syndrome (PMS) is selective serotonin reuptake inhibitors (SSRIs), particularly fluoxetine (Prozac), as it is FDA approved for premenstrual dysphoric disorder and has been shown to be effective in managing symptoms of PMS 1.

Key Considerations

  • Fluoxetine is typically prescribed at a standard antidepressant dose of 20mg daily and can be taken continuously or just during the luteal phase (two weeks before menstruation) 1.
  • SSRIs, including fluoxetine, work by increasing serotonin levels in the brain, which helps regulate mood, appetite, and sleep patterns that are often disrupted during PMS.
  • For women who cannot tolerate SSRIs, hormonal options like combined oral contraceptives (particularly those containing drospirenone like Yaz or Yasmin) may be considered.

Non-Pharmacological Approaches

  • Regular exercise, stress management, and dietary changes (reducing caffeine, salt, and alcohol) should be implemented alongside medication therapy for optimal symptom management.

Important Notes

  • Fluoxetine and other SSRIs can have potential side effects, and it is essential to monitor patients for treatment-emergent suicidality, particularly in adolescents and young adults 1.
  • Genetic variation, particularly in cytochrome P450 2D6 (CYP2D6), can affect the metabolism of fluoxetine and other SSRIs, and pharmacogenetic guidelines may be necessary to individualize treatment selection 1.

From the FDA Drug Label

It is also marketed for the treatment of premenstrual dysphoric disorder (Sarafem®, fluoxetine hydrochloride). The drug of choice for Premenstrual Syndrome (PMS), more specifically premenstrual dysphoric disorder, is fluoxetine 2.

From the Research

Drug of Choice for Premenstrual Syndrome (PMS)

The drug of choice for PMS is often considered to be Selective Serotonin Reuptake Inhibitors (SSRIs) due to their effectiveness in reducing symptoms.

  • SSRIs have been shown to be effective in reducing overall self-rated symptoms of PMS, with a moderate effect size when taken in the luteal phase or continuously 3.
  • Studies have demonstrated that SSRIs such as fluoxetine, paroxetine, sertraline, escitalopram, and citalopram are effective in treating PMS symptoms, including psychological, physical, and functional symptoms 3, 4, 5.
  • A double-blind trial comparing four medications, including fluoxetine, found that fluoxetine (10 mg) obtained a mean reduction of 65.4% in symptoms, making it the most effective treatment for severe PMS 6.

Commonly Used SSRIs for PMS

Some commonly used SSRIs for PMS include:

  • Fluoxetine: shown to be effective in reducing PMS symptoms, including behavioral, physical, and total symptoms 4, 6.
  • Citalopram: demonstrated to be effective in PMS patients who did not respond to previous SSRI treatment, with significant improvement in total premenstrual symptoms and symptom clusters 5.
  • Sertraline: found to be effective in reducing PMS symptoms, although the evidence is not as extensive as for fluoxetine and citalopram 3.

Adverse Effects of SSRIs

While SSRIs are effective in treating PMS, they can cause adverse effects, including:

  • Nausea: a common side effect associated with a moderate dose of SSRIs 3.
  • Asthenia or decreased energy: another common side effect associated with a moderate dose of SSRIs 3.
  • Somnolence, fatigue, decreased libido, and sweating: also reported as side effects of SSRIs, although less frequently than nausea and asthenia 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Selective serotonin reuptake inhibitors for premenstrual syndrome.

The Cochrane database of systematic reviews, 2013

Research

Citalopram in PMS patients with prior SSRI treatment failure: a preliminary study.

Journal of women's health & gender-based medicine, 2002

Research

A double-blind trial of four medications to treat severe premenstrual syndrome.

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 1998

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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