Triptans are more effective at relieving migraine pain than newer, more expensive drugs

The researchers recommend that these triptans be included on the WHO Essential Medicines List to facilitate global dissemination, improve access and standardize treatment.

In a recently published meta-analysis, BMJThe researchers compared oral medications approved as monotherapy for the acute management of migraine attacks in adults.

background

Migraine is a common neurological disorder characterized by moderate or severe headache lasting for many days. Migraine affects an individual's health, productivity, and socio-economic impact. Pharmacological treatment of acute migraine headaches provides immediate pain relief.

Regulatory authorities recommend nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line therapy, with triptans reserved for moderate to severe attacks or inadequate response. Patients in whom triptans are contraindicated due to possible vasoconstrictor effects or who are at high risk for cardiovascular disease may prefer more recently marketed drugs such as lasmiditan or gepant. However, there is no universal consensus on the ranking of migraine medications.

About the Research

This meta-analysis provides comprehensive information on medications used to manage acute migraine attacks in adults.

Data sources included the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Medline, ClinicalTrials.gov, the World Health Organization (WHO) Clinical Trials Registry, and the European Union (EU) Clinical Trials Registry. The researchers searched pharmaceutical company and regulatory agency websites up to June 24, 2023, with no language restrictions.

Included studies were double-blind randomized controlled trials (RCTs) evaluating orally administered medications as monotherapy for migraine compared with placebo or other active medications for managing acute migraine attacks in adults. Narcotic use was not investigated and no emergency department evaluations were performed. Migraine diagnosis was according to International Classification of Headache Disorders (ICHD) criteria. International regulatory agencies recommend these medications for migraine.

Data were screened and extracted by two independent researchers. Disagreements between team members were resolved through discussion. The second version of the Cochrane risk of bias tool (RoB2) indicated the risk of bias in included studies. The reliability of network meta-analyses (CINeMA) tool assessed the certainty of evidence.

Primary study outcomes included the proportion of people who were pain-free 2 hours after taking the drug and the proportion of people who were pain-free 2 hours to 1 day after administration without the use of rescue medication. Secondary outcomes were pain relief 2 hours after taking the drug, pain recurrence 2 hours to 2 days, and use of rescue medication 2 hours to 24 hours after the intervention. Other outcomes included the tolerability and safety of the drug intervention.

Primary data were analyzed using random-effects network meta-analysis. Odds ratios (OR) indicate the magnitude of treatment effect. Researchers incorporated public input and feedback from migraine sufferers. Researchers presented their results to expert clinicians and patient representatives from international institutions in Argentina, Canada, Europe, and the United States (US).

result

The meta-analysis included 137 RCTs, involving 89,445 participants. The mean age of participants was 40 years, 86% were women, and 32% experienced migraine with aura. The certainty of the evidence ranged from high to very low. For the assessment of pain relief, 21% of RCTs were at low risk of bias and 16% were at high risk of bias. For sustained pain relief, 29% of RCTs were at low risk of bias and 11% were at high risk of bias.

All treatments were more effective than placebo in reducing pain at 2 hours (ORs ranged from 1.7 for naratriptan to 5.2 for eletriptan). efficacy Eletriptan was most effective in relieving pain over 24 hours (OR 1.7 for celecoxib and 7.6 for ibuprofen). Eletriptan was most effective in providing pain relief over 2 hours (OR 1.5-3.0). Other highly effective drugs were rizatriptan (OR 1.6-2.4), sumatriptan (OR 1.4-2.0), and zolmitriptan (OR 1.5-2.0). Eletriptan and ibuprofen were most effective in providing long-term pain relief (OR 1.4-4.8).

All interventions were more effective at providing pain relief after 2 hours and rescue medication after 2 to 24 hours. Eletriptan was most effective at providing pain relief after 2 hours (OR 1.3 to 2.6) and rescue medication (OR 0.4 to 0.6). Side effects of eletriptan use included dizziness, fatigue, sedation, and chest discomfort. Rimegepant was well tolerated, but ubrogepant caused more nausea than placebo. Participants reported dizziness, paresthesia, and sedation after using lasmiditan.

The team found similar results in a sensitivity analysis that included only studies with FDA-approved doses and low bias: participants in these trials experienced moderate or severe headaches, had no comorbidities, and were not using preventive medications.

Conclusion

Findings indicate that triptans, including rizatriptan, eletriptan, zolmitriptan, and sumatriptan, are the most effective and well-tolerated medications for the acute treatment of migraine in adults. These medications are more effective than recently marketed medications (ubrogepant, lasmiditan, and rimegepant) that have shown efficacy comparable to NSAIDs. Inclusion of high-potency triptans on the WHO essential medicines list could improve access and treatment globally. Cost-effectiveness analyses are needed to inform clinical decision-making.