Evidence Matters

Meta-Analysis: Which Migraine Treatment Methods Are Most Effective?

BACKGROUND AND PURPOSE:

Gartlehner et al. (Annals of Internal Medicine, 2025) compared benefits and harms of pharmacologic treatments for acute attacks of episodic migraine in adults

Systematic review and meta-analysis
Inclusion criteria
- Head-to-head and placebo-controlled trials
- Studies that included adult patients who received initial treatment or second-step treatment for acute attacks of episodic migraine, comparing pharmacologic interventions to other interventions or placebo
Study design
- Risk of bias was assessed
- Certainty of evidence was assessed with GRADE criteria
Primary outcomes
- Pain freedom at 2 hours and 48 hours
- Need for rescue medication
- Nausea or vomiting

21 head-to-head studies | 164 placebo-controlled trials
Triptans were more effective than acetaminophen and NSAIDS for pain outcomes at 2 hours and pain freedom at 48 hours
- Pain freedom at 2 hours, compared to acetaminophen
  - Absolute risk difference (ARD) 0.16 (95% CI, 0.02 to 0.38)
  - Risk ratio (RR) 1.64 (95% CI, 1.08 to 2.49)
  - Low certainty
- Pain freedom at 2 hours, compared to NSAIDs
  - ARD 0.10 (95% CI, 0.06 to 0.16)
  - RR 1.42 (95% CI, 1.23 to 1.65)
  - High certainty
Triptan and acetaminophen combinations were more effective than acetaminophen alone
- ARD 0.30 (95% CI, 0.04 to 0.74)
- RR 2.17 (95% CI, 1.17 to 4.03)
- Moderate certainty
Triptan and acetaminophen combinations were not more effective than a triptan alone
- ARD 0.13 (95% CI, –0.10 to 0.53)
- RR 1.33 (95% CI, 0.75 to 2.34)
- Low certainty
Triptan and NSAID combinations were more effective for pain outcomes at 2 hours and pain freedom up to 48 hours compared with
- Acetaminophen (low COE)
  - RR 1.91 (95% CI, 1.21 to 3.00)
  - Low certainty
- Gepants
  - RR 1.96 (95% CI, 1.50 to 2.56)
  - Low certainty
- NSAIDs
  - ARD 0.11 (95% CI, 0.06 to 0.17)
  - RR 1.66 (95% CI, 1.35 to 2.05)
  - High certainty
- Triptan monotherapy
  - ARD 0.04 (95% CI, –0.01 to 0.09)
  - RR 1.17 (95% CI, 0.97 to 1.40)
  - Moderate certainty
Triptans had a higher risk of adverse events
One study found triptans more cost-effective than ditan and gepant

When treating episodic migraine, triptans or a combination or triptan and NSAID was most effective at achieving pain relief at 2 hours and sustained pain freedom at 48 hours
These findings are reflected in the new ACP migraine guidelines (see ‘Learn More – Primary Sources’ below)