What is the best treatment approach for a premenopausal female experiencing agitation and anxiety related to premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) a week before her period?

Treatment for Premenstrual Agitation and Anxiety

For premenopausal women experiencing agitation and anxiety one week before their period, SSRIs are the first-line pharmacological treatment, with sertraline 50-150 mg/day being FDA-approved and highly effective for premenstrual dysphoric disorder (PMDD), while cognitive behavioral therapy (CBT) should be initiated concurrently as it significantly reduces functional impairment, depressed mood, and anxiety. 1, 2, 3

Initial Assessment and Diagnosis

Before initiating treatment, you must confirm the temporal pattern of symptoms:

• Symptoms must begin several days before menses, improve within a few days after menses onset, and become minimal or absent within one week following menses 1
• Have the patient track symptoms prospectively for at least two menstrual cycles using the Daily Record of Severity of Problems (DRSP) to confirm the cyclic pattern 4
• Rule out thyroid disease and diabetes, as hypothyroidism can present with mood changes and fatigue that mimic premenstrual symptoms 2

Treatment Algorithm

First-Line: Combined Approach

Start with both lifestyle modifications AND pharmacotherapy for moderate-to-severe symptoms:

Lifestyle Modifications (initiate immediately):

• Cognitive behavioral therapy (CBT) reduces functional impairment, depressed mood, and anxiety in PMDD patients, with benefits maintained at 3-month follow-up 1, 2
• Regular physical activity of 150 minutes per week of moderate intensity provides overall health benefits 2
• Weight loss of ≥10% body weight if overweight can eliminate symptoms 2
• Smoking cessation improves frequency and severity of symptoms 2

Pharmacotherapy (SSRIs as first-line):

Sertraline is FDA-approved specifically for PMDD and has two dosing options:

• Continuous dosing: Start 50 mg/day throughout the entire menstrual cycle, can increase to 150 mg/day based on response 3
• Luteal phase dosing: Start 50 mg/day for the last 2 weeks of the cycle (luteal phase), can increase to 100 mg/day 3

Continuous dosing is more effective than luteal phase dosing (SMD -0.69 vs -0.39), so prefer continuous administration unless the patient specifically requests intermittent dosing 5

Alternative SSRIs if sertraline is not tolerated:

• Fluoxetine 10-20 mg/day 6
• Escitalopram 10-20 mg/day 6
• Controlled-release paroxetine 12.5-25 mg/day (FDA-approved), but avoid in women who may need tamoxifen due to CYP2D6 inhibition 2, 6

Second-Line: SNRI Alternative

If SSRIs are not tolerated or ineffective:

• Venlafaxine reduces symptom intensity by 40-65% and is particularly useful when SSRIs cause intolerable side effects 2

Third-Line: Hormonal Suppression

Consider hormonal interventions only after SSRIs/SNRIs have failed:

• Hormonal interventions that suppress ovulation (such as GnRH analogs) can eliminate premenstrual symptoms by preventing luteal phase hormonal fluctuations 1
• Important contraindications include: history of hormone-dependent cancers, history of thromboembolic events, active liver disease, and abnormal vaginal bleeding 2
• Do not use combined oral contraceptives as first-line for mood symptoms, as they primarily address physical symptoms 2

Expected Adverse Effects and Management

Patients taking SSRIs should be counseled about common adverse effects:

• Nausea (most common, OR 3.30) 5
• Insomnia (OR 1.99) 5
• Sexual dysfunction or decreased libido (OR 2.32) 5
• Asthenia or decreased energy (OR 3.28) 5
• Somnolence and decreased concentration (OR 3.26) 5
• Dizziness or vertigo (OR 1.96) 5

These adverse effects are generally well-tolerated and do not lead to higher discontinuation rates compared to placebo 7, 5

Common Pitfalls to Avoid

• Do not rely solely on patient recall of symptoms—always require prospective tracking for at least two cycles, as symptoms can vary cycle to cycle 4
• Avoid paroxetine in women of reproductive age who may later require tamoxifen for breast cancer, as it inhibits CYP2D6 and reduces tamoxifen efficacy 2
• Do not use custom-compounded bioidentical hormones, as no data support claims of superior safety or efficacy 2
• Reassess for another underlying cause if symptoms persist throughout the month or are not controlled with medications 4

Monitoring and Follow-Up

• SSRIs have rapid onset of improvement, often within the first treatment cycle 4
• Reassess response after 2-3 menstrual cycles 3
• If inadequate response at 50 mg/day, increase dose incrementally up to maximum of 150 mg/day (continuous) or 100 mg/day (luteal phase) 3
• Given the 24-hour elimination half-life of sertraline, dose changes should not occur at intervals of less than 1 week 3