Best NSAID for Dysmenorrhea
Ibuprofen 400 mg every 4-6 hours is the recommended first-line NSAID for dysmenorrhea, offering the best balance of efficacy and safety with the lowest gastrointestinal risk among NSAIDs. 1, 2
Primary Recommendation: Ibuprofen
- Ibuprofen is specifically FDA-approved for dysmenorrhea at 400 mg every 4 hours as necessary, beginning with the earliest onset of pain 1
- Ibuprofen demonstrates superior efficacy compared to placebo with an odds ratio of 10.08 (95% CI 3.29-30.85), ranking second highest for effectiveness among all NSAIDs studied 2
- Ibuprofen has the lowest gastrointestinal ulcerogenic risk among all non-selective NSAIDs, making it the safest choice for repeated menstrual cycle use 3
- Network meta-analysis ranking ibuprofen as having 79.6% probability of being the safest NSAID (second only to ketoprofen at 90.6%), while maintaining 83.8% probability of being most effective (second to diclofenac at 85.1%) 2
Alternative First-Line Option: Naproxen
- Naproxen sodium 550 mg taken 1-2 hours before expected pain onset provides optimal timing to align with peak effect 4
- Naproxen 400 mg provides greater pain relief than acetaminophen within 30 minutes (P < 0.01) and superior relief to both acetaminophen and ibuprofen 200 mg at 6 hours (P < 0.01) 5
- Naproxen's longer half-life makes it particularly suitable for dysmenorrhea, as it requires less frequent dosing than ibuprofen 3
- Both naproxen 400 mg and 200 mg demonstrated higher scores than placebo for symptom relief and drug preference (all P < 0.001) 5
Clinical Decision Algorithm
Step 1: Initial Treatment
- Start with ibuprofen 400 mg every 4-6 hours, beginning at earliest symptom onset 1
- Alternative: naproxen sodium 550 mg taken 1-2 hours before expected pain 4
Step 2: If Inadequate Response
- Consider naproxen if ibuprofen fails, given its longer duration of action 3, 5
- Alternatively, try ketoprofen 20 mg orally 40-60 minutes before expected pain for faster onset 4
Step 3: Safety Considerations
- Ibuprofen remains the lowest-risk NSAID for serious gastrointestinal complications across all NSAIDs studied 3, 6
- All NSAIDs carry 1.29 times higher risk of adverse effects compared to placebo (95% CI 1.11-1.51), with gastrointestinal effects at OR 1.58 and neurological effects at OR 2.74 7
- Use the lowest effective dose for the shortest duration (typically 2-3 days per menstrual cycle) 3, 8
Evidence Regarding Other NSAIDs
Diclofenac:
- Highest efficacy ranking (85.1% SUCRA probability) but also highest adverse effect profile among commonly used NSAIDs 2
- Not recommended as first-line due to increased cardiovascular risk compared to other NSAIDs 9
Ketoprofen:
- Best safety profile (90.6% SUCRA probability) but less readily available and less studied than ibuprofen 2
- FDA-approved for dysmenorrhea but not as widely accessible 10
Aspirin:
- Significantly less effective than ibuprofen (OR 0.17,95% CI 0.04-0.73) and diclofenac (OR 1.17,95% CI 0.02-0.85) 2
- Not recommended for dysmenorrhea 2
Important Clinical Caveats
- NSAIDs work by blocking prostaglandin synthesis, which is the primary mechanism of dysmenorrhea pain 8, 7
- Treatment should begin at the earliest onset of menstrual symptoms or pain, not after pain is established 1, 8
- Approximately 80% of women with significant primary dysmenorrhea achieve adequate relief with effective NSAIDs 8
- NSAIDs are more effective than paracetamol/acetaminophen for dysmenorrhea (OR 1.89,95% CI 1.05-3.43) 7
- All NSAIDs should be avoided after 28 weeks gestation due to risk of premature ductus arteriosus closure and oligohydramnios 3
- Ibuprofen, indomethacin, and naproxen are safe to use in breastfeeding women 3
When to Avoid NSAIDs
- History of peptic ulcer disease or gastrointestinal bleeding 3
- Concurrent anticoagulant or antiplatelet therapy (increases bleeding risk 5-6 fold) 3
- Renal insufficiency or compromised fluid status 3
- Known cardiovascular disease (if NSAIDs must be used, naproxen preferred over diclofenac) 3, 9
- Pregnancy beyond first trimester 3