Triptans work best against migraine episodes

For adults with migraine, the drugs with the best profile include eletriptan, rizatriptan, sumatriptan, and zolmitriptan, suggests a study. These agents are more effective than most available medications on the market such as lasmiditan, rimegepant, and ubrogepant.

“Although cost effectiveness analyses are warranted and careful consideration should be given to patients with a high-risk cardiovascular profile, the most effective triptans should be considered as preferred acute treatment for migraine and included in the WHO List of Essential Medicines to promote global accessibility and uniform standards of care,” the investigators said.

This systematic review and network meta-analysis obtained data with no language restrictions until 24 June 2023 from the following sources: Cochrane Central Register of Controlled Trials, Medline, Embase, ClinicalTrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, and websites of regulatory agencies and pharmaceutical companies.

The investigators independently performed screening, data extraction, coding, and risk of bias assessment in duplicate, as well as conducted random effects network meta-analyses for the primary analyses. They graded evidence certainty using the confidence in network meta-analysis online tool and summarized the findings via Vitruvian plots.

Some 137 randomized controlled trials consisting of 89,445 participants allocated to one of 17 active interventions of placebo met the eligibility criteria. [BMJ 2024;386:e080107]

All agents assessed were superior to placebo in terms of pain freedom at 2 hours. Odds ratios [OR] ranged from 1.73 (95 percent confidence interval [CI], 1.27‒2.34) for naratriptan to 5.19 (95 percent CI, 4.2‒6.33) for eletriptan.

Most of the active interventions also showed superior efficacy over placebo for sustained pain freedom to 24 hours. ORs ranged from 1.71 (95 percent CI, 1.07‒2.74) for celecoxib to 7.58 (95 percent CI, 2.58‒22.27) for ibuprofen.

Eletriptan supremacy

Head-to-head comparisons between active interventions found eletriptan to be the most effective drug for pain freedom at 2 hours, with ORs ranging from 1.46 (95 percent CI, 1.18‒1.81) to 3.01 (95 percent CI, 2.13‒4.25). This was followed by rizatriptan (ORs from 1.59, 95 percent CI, 1.18‒2.17 to 2.44, 95 percent CI, 1.75‒3.45), sumatriptan (ORs from 1.35, 95 percent CI, 1.03‒1.75 to 2.04, 95 percent CI, 1.49‒2.86), and zolmitriptan (ORs from 1.47, 95 percent CI, 1.04‒2.08 to 1.96, 95 percent CI, 1.39‒2.86).

Eletriptan was also the most efficacious agent, together with ibuprofen, for sustained pain freedom, with ORs ranging from 1.41 (95 percent CI, 1.02‒1.93) to 4.82 (95 percent CI, 1.31‒17.67).

In addition, “[c]onfidence in accordance with CINeMA ranged from high to very low,” the investigators said. “Sensitivity analyses on Food and Drug Administration licensed doses only, high versus low doses, risk of bias, and moderate to severe headache at baseline confirmed the main findings for both primary and secondary outcomes.”

The results of this study are consistent with recent observational evidence. Careful comparisons between these trials and observational findings may be done in future research, which can help inform clinical decision making, according to the investigators. [Neurology 2023;101:e2560-2570; JAMA 2023;329:1352-1353]

“Triptans are selective serotonin (5 hydroxytryptamine)1B/1D receptor agonists, exhibiting differences in receptor affinity, lipophilicity, metabolism, and pharmacokinetic profiles within the same class,” they noted. [Nat Rev Dis Primers 2022;8:2]