Triptans relieve migraine pain better than newer and more expensive medications

Researchers are pushing for global promotion of these triptans and recommending their inclusion on the WHO's list of essential medicines to improve availability and standardize treatment.

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

background

Migraine is a common neurological disorder characterized by recurrent headaches of moderate to severe intensity that may last for several days. It affects personal well-being, productivity and has socioeconomic consequences. Acute treatment of the disorder involves medications that provide immediate pain relief.

Regulatory authorities recommend nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line therapy, with triptans reserved for moderate and severe attacks or inadequate response. Patients in whom the use of triptans is contraindicated due to likely vasoconstrictor effects, or those at high risk for cardiovascular disease, may prefer newly launched drugs such as lasmiditan and gepants. However, there is no general consensus on the ranking of drugs for treating migraine.

About the study

The present meta-analysis provides comprehensive information on medications used to treat acute migraine episodes 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 Register. The researchers also searched pharmaceutical company and regulatory agency websites with no language restrictions until June 24, 2023.

The included studies were double-blind randomized controlled trials (RCTs) evaluating oral medications as monotherapy for migraine compared with placebo or other active therapeutics for the treatment of acute migraine episodes in adults. Opiate use was not assessed and no emergency department visits were performed. Migraine diagnosis was made according to the International Classification of Headache Disorders (ICHD) criteria. International regulatory authorities recommend these medications for migraine.

Two independent researchers reviewed and extracted the data. Disagreements between them were resolved through discussions with team members. The second version of the Cochrane Risk of Bias Tool (RoB2) indicated a risk of bias in the included studies. The Confidence in Network Meta-Analysis (CINeMA) tool assessed the certainty of the evidence.

Primary study outcomes included the percentage of people who were pain-free two hours after taking the drug and those who were pain-free two hours to one day after taking the dose without the use of rescue medication. Secondary outcomes were pain relief two hours after taking the drug, pain relapse within two hours to two days, and the use of rescue medication two hours to 24 hours after the intervention. Other outcomes included the tolerability and safety of the drug interventions.

Primary data were analyzed in meta-analyses using random effects networks. Odds ratios (ORs) indicated the strength of treatment effects. The researchers incorporated public input and feedback from migraine patients into their studies. They presented the results to clinical experts and patient representatives from international organizations in Argentina, Canada, Europe, and the United States (US).

Results

The meta-analysis included 137 randomized controlled trials with 89,445 participants whose mean age was 40 years; 86% were female and 32% had migraine with aura. The reliability of the evidence ranged from high to very low. The risk of bias in assessing pain relief was low in 21% of randomized controlled trials and high in 16% of randomized controlled trials. In assessing sustained pain relief, the risk of bias was low in 29% of randomized controlled trials and high in 11% of randomized controlled trials.

All therapies were more effective than placebo in reducing pain after two hours (OR ranging from 1.7 for naratriptan to 5.2 for eletriptan). Most interventions also showed greater efficacy in reducing pain for 24 hours (OR ranging from 1.7 for celecoxib to 7.6 for ibuprofen). Eletriptan showed the highest efficacy for two-hour pain relief (OR 1.5 to 3.0). Other highly effective drugs were rizatriptan (OR 1.6 to 2.4), sumatriptan (OR 1.4 to 2.0) and zolmitriptan (OR 1.5 to 2.0). Eletriptan and ibuprofen were most effective for long-term pain relief (OR 1.4 to 4.8).

All interventions showed better pain relief than placebo at two hours and better efficacy than rescue medication at two to 24 hours. Eletriptan was most effective in reducing pain at two hours (OR of 1.3 to 2.6) and compared with rescue medication (OR of 0.4 to 0.6). Side effects of eletriptan use included dizziness, fatigue, sedation, and chest discomfort. Rimegepant was well tolerated, while ubrogepant caused more nausea than placebo. Participants reported dizziness, paresthesia, and sedation after using lasmiditan.

The team reached similar conclusions in sensitivity analyses, which included only doses approved by the US Food and Drug Administration (FDA) and studies with low bias. Participants in these studies suffered from moderate or severe headaches, had no comorbidities and were not taking any preventive medications.

Diploma

The results showed 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 launched medications (ubrogepant, lasmiditan and rimegepant) that showed efficacy comparable to NSAIDs. The inclusion of highly effective triptans in the WHO List of Essential Medicines could improve global access and supply. Cost-effectiveness analyses are needed to support clinical decisions.