What are the treatment options for premenstrual mood changes?

Treatment of Premenstrual Mood Changes

For premenstrual mood changes, selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment, with fluoxetine, sertraline, and controlled-release paroxetine being FDA-approved for premenstrual dysphoric disorder (PMDD). 1, 2, 3

Initial Assessment

Before initiating treatment, evaluate for alternative medical causes that can mimic premenstrual symptoms:

• Check thyroid function (hypothyroidism can present with mood changes and fatigue) 4
• Screen for diabetes (can affect mood and energy levels) 4
• Consider laboratory evaluation including estradiol, FSH, LH, and prolactin if diagnosis is unclear 4

The diagnosis requires prospective symptom tracking using the Daily Record of Severity of Problems, documenting that symptoms occur during the luteal phase and resolve within days of menstruation onset 2. Premenstrual syndrome (PMS) affects 30-40% of reproductive-age women, while PMDD affects 3-8% 2.

Treatment Algorithm

First-Line: Lifestyle Modifications (All Patients)

Start with non-pharmacological interventions for mild-to-moderate symptoms:

• Weight loss of ≥10% body weight if overweight can eliminate hot flash symptoms and improve mood 4
• Smoking cessation improves frequency and severity of symptoms 4
• Limit alcohol intake if it triggers symptoms in individual patients 4
• Cognitive behavioral therapy (CBT) reduces the perceived burden of premenstrual symptoms 4, 5
• Regular physical activity (150 minutes per week of moderate intensity) for overall health benefits 4

CBT alone has demonstrated significant positive benefits that continue throughout treatment and are maintained at 3-month follow-up, unlike hormone therapy which shows diminishing effects after 2 months 5.

Second-Line: Pharmacological Treatment

SSRIs (First-Line Pharmacotherapy)

SSRIs are the drugs of choice for improving both physical and mood symptoms 2, 3:

• Fluoxetine (FDA-approved): 20 mg daily or intermittent luteal phase dosing 1, 3
• Sertraline (FDA-approved): Effective for PMDD 3
• Controlled-release paroxetine (FDA-approved): Effective but avoid in women who may need tamoxifen due to CYP2D6 inhibition 4, 3

SSRIs can be dosed continuously or only during the luteal phase (14 days before expected menses), with both strategies showing efficacy 3. The advantage of SSRIs is their effectiveness for both emotional and physical symptoms, unlike hormonal therapies which primarily target physical symptoms 2.

SNRIs (Alternative First-Line)

• Venlafaxine reduces symptom intensity by 40-65% and is particularly useful when SSRIs are not tolerated 4, 6

Third-Line: Hormonal Suppression

Combined oral contraceptives (COCs) primarily improve physical symptoms rather than mood symptoms 2. Consider hormonal therapy when:

• SSRIs or SNRIs are ineffective or not tolerated 3
• Patient desires contraception 3
• Physical symptoms predominate over mood symptoms 2

Important contraindications to hormonal therapy 7, 4:

• History of hormone-dependent cancers
• History of thromboembolic events
• Active liver disease
• Abnormal vaginal bleeding

Adjunctive Treatments for Specific Symptoms

• Anxiolytics for severe anxiety symptoms (as supportive care) 3
• Spironolactone for bloating and fluid retention 3
• NSAIDs for physical pain symptoms 3
• Calcium supplementation (1200 mg daily) has shown efficacy in reducing emotional, behavioral, and physical premenstrual symptoms in placebo-controlled trials 8

Special Considerations

Severe PMDD

For women with severe, disabling PMDD unresponsive to SSRIs and hormonal therapy:

• Gonadotropin-releasing hormone (GnRH) agonists suppress ovulation and alleviate symptoms, but prolonged use carries cardiac and osteoporotic risks due to low estrogen levels 8
• This should be reserved for refractory cases under specialist management 8

Comorbid Bipolar Disorder

If bipolar disorder is suspected or diagnosed, stabilize bipolar symptoms first with mood stabilizers before treating PMDD symptoms 9. In euthymic bipolar patients, hormonal contraceptives can be considered as first-line for PMDD symptoms, while antidepressants should be used cautiously only during acute depressive episodes with mood stabilizer coverage 9.

Common Pitfalls to Avoid

• Do not use COCs as first-line for mood symptoms—they primarily address physical symptoms and do not restore spontaneous menses 7, 2
• Avoid paroxetine in women of reproductive age who may later require tamoxifen for breast cancer, as it inhibits CYP2D6 and reduces tamoxifen efficacy 4
• Do not rely on FSH levels in women with prior chemotherapy or pelvic radiation, as FSH is unreliable in these populations 4
• Avoid custom-compounded bioidentical hormones—no data support claims of superior safety or efficacy compared to standard hormone therapies 4
• Herbal supplements and vitamin E have unclear or conflicting evidence and should not be recommended as primary treatment 3