A comprehensive network meta-analysis comparing oral medications for acute migraine treatment found that certain triptans demonstrated superior efficacy and tolerability compared to newer agents.
The study, published in The BMJ, analyzed data from 137 randomized controlled trials, including 89,445 participants. Researchers compared 17 oral monotherapy drugs across multiple outcomes. Key findings included:
Eletriptan, rizatriptan, sumatriptan, and zolmitriptan showed the most favorable overall profiles for efficacy and tolerability. They were more effective when compared to the recently approved drugs lasmiditan, rimegepant, and ubrogepant. The newer drugs showed efficacy comparable to paracetamol and most NSAIDs. All active interventions were superior to placebo for pain freedom at 2 hours post-dose.
For the primary outcome of pain freedom at 2 hours, odds ratios versus placebo ranged from 1.73 (95% CI, 1.27-2.34) for naratriptan to 5.19 (95% CI, 4.25-6.33) for eletriptan. In head-to-head comparisons, eletriptan was most effective (ORs 1.46-3.01 vs other drugs), followed by rizatriptan, sumatriptan, and zolmitriptan.
Regarding sustained pain freedom from 2-24 hours, eletriptan and ibuprofen were most efficacious (ORs 1.41-4.82 vs other drugs).
For tolerability, lasmiditan was associated with an increased risk of dizziness, fatigue, and sedation. Eletriptan showed higher rates of chest pain. Newer agents rimegepant and ubrogepant demonstrated favorable tolerability overall.
The systematic review searched multiple databases through June 2023 without language restrictions. Inclusion criteria were double-blind randomized trials in adults with migraine comparing oral monotherapy drugs to placebo or another eligible treatment. Only drugs and doses licensed by major regulatory agencies were included.
Of the 184 trials identified, 174 (95%) were industry-sponsored, 163 (89%) were placebo-controlled, and 52 (28%) directly compared at least 2 active interventions. The median study sample size was 378 participants (interquartile range 132-690). Participants had a mean age of 40.3 years (SD 10.9), 85.6% were female, and 32.3% had a history of migraine with aura.
While eletriptan and other triptans showed strong efficacy, the researchers highlighted that the certainty of evidence varied, with many comparisons showing low or very low certainty, particularly for newer drugs like rimegepant.
Specific adverse events included paraesthesia, more common with lasmiditan (ORs 1.28-1.50), sumatriptan (OR vs placebo 1.18; 95% CI, 1.04-1.32), and zolmitriptan (ORs 1.18-1.50). Chest pain was more frequent with eletriptan (ORs 1.42-1.78), while paracetamol showed an increased risk of hepatic toxicity (ORs 6.40-7.69).
Limitations included moderate heterogeneity for most outcomes and low to very low confidence in many comparisons due to a lack of prespecified analysis plans, imprecision, or incomplete reporting on randomization methods.
Conflict of interest disclosures can be found in the published article.