What is the most appropriate medication to start for a female patient with premenstrual symptoms, including a throbbing abdominal sensation, fatigue, diarrhea, and nausea, who is not sexually active and is currently taking sertraline (Selective Serotonin Reuptake Inhibitor - SSRI) for mental health?

Treatment Recommendation for Premenstrual Symptoms

Start naproxen 500 mg initially, followed by 250 mg as needed (maximum 1250 mg daily), beginning at the first sign of symptoms before menstruation. 1

Clinical Reasoning

This patient presents with classic perimenstrual symptoms including throbbing abdominal pain, fatigue, diarrhea, and nausea occurring predictably 1 day before menses and resolving within 36 hours. The symptom pattern and timing strongly suggest either primary dysmenorrhea with premenstrual symptoms or premenstrual dysphoric disorder (PMDD). 2, 3

Why Naproxen is the Optimal Choice

For perimenstrual preventive treatment, NSAIDs like naproxen are the first-line recommendation, particularly when physical symptoms (pain, gastrointestinal distress) predominate. 1 The evidence supporting naproxen is compelling:

• Efficacy data: In women with severe primary dysmenorrhea, naproxen reduced tablet consumption from 17.8 to 5.1 per menstruation, decreased bed rest from 16.4 to 1.2 hours, and reduced sick leave from 40 to 7 days per two menstruations (P < 0.001). 2

• Mechanism: Prostaglandin inhibitors address the underlying pathophysiology of both dysmenorrhea and many premenstrual symptoms by blocking excessive prostaglandin production in the brain, breast, gastrointestinal tract, kidney, and reproductive tract. 3

• Guideline support: For women with menstrual-related symptoms, perimenstrual preventive treatment typically involves daily intake of a long-acting NSAID (specifically naproxen) for 5 days, beginning 2 days before the expected first day of menstruation. 1

Why Other Options Are Less Appropriate

Letrozole (A): An aromatase inhibitor with no indication for premenstrual symptoms or dysmenorrhea. This is not appropriate for this clinical scenario.

Hyoscyamine (B): An anticholinergic antispasmodic that may help with cramping but does not address the broader symptom complex (fatigue, nausea, diarrhea) and lacks evidence for premenstrual symptoms. 1

Magnesium (C): While sometimes used for premenstrual symptoms, it lacks the robust evidence base that NSAIDs possess for this symptom pattern. 2, 3

Nifedipine (E): A calcium channel blocker with no role in treating premenstrual symptoms or dysmenorrhea.

Important Consideration: The Sertraline Factor

The patient is already taking sertraline, which is highly relevant if symptoms worsen or fail to respond to NSAIDs. If the patient's symptoms represent PMDD rather than simple dysmenorrhea, sertraline is already an appropriate medication. 4, 5, 6

• Sertraline at 50-150 mg daily has demonstrated significant efficacy for PMDD, with 62% showing much or very much improvement versus 34% with placebo (P < 0.001). 4

• Intermittent luteal phase dosing (50-100 mg daily during symptomatic days only) is also effective, with 50% responder rates versus 26% for placebo (P < 0.001). 6

• However, the current presentation emphasizes physical symptoms (throbbing pain, diarrhea) over mood symptoms, making NSAIDs the more targeted initial approach. 1, 2

Treatment Algorithm

1. Start naproxen 500 mg at first sign of symptoms, then 250 mg as needed (max 1250 mg/day) for up to 5 days per cycle. 1, 2

2. If inadequate response after 2-3 cycles: Consider optimizing sertraline dosing (ensure at least 50 mg daily) or switching to continuous daily dosing if currently intermittent. 4, 6

3. If predominantly mood symptoms emerge: Increase sertraline to therapeutic doses (50-150 mg daily) rather than adding additional agents. 7, 4

4. Monitor for: Changes in bleeding pattern (naproxen can affect menstrual flow in some women), gastrointestinal side effects, and any worsening of mood symptoms. 2

Critical Pitfalls to Avoid

• Do not combine multiple serotonergic agents with sertraline without careful monitoring for serotonin syndrome risk. 1

• Do not exceed naproxen 1250 mg daily or use continuously without gastroprotection if risk factors for GI bleeding exist. 2

• Do not assume treatment failure before allowing at least 2-3 menstrual cycles to assess response, as symptom patterns may vary cycle-to-cycle. 1

• Do not overlook the possibility of PMDD if mood symptoms become prominent; in that case, the existing sertraline regimen should be optimized rather than abandoned. 4, 5, 6

Answer: D) Naproxen