Triptans better at relieving migraine pain than recently marketed and more expensive drugs

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Sep 23 2024

Researchers urge global promotion of these triptans and recommend their inclusion in the WHO Essential Medicines List to improve accessibility and standardize care.

In a recent meta-analysis published in BMJ, researchers compared oral drugs licensed as monotherapies for the acute management of migraine episodes among adults.

Background

Migraine, a prevalent neurological illness, is characterized by recurrent headaches of moderate or severe intensity that can continue for days. It influences personal well-being, productivity, and socioeconomic consequences. Acute management of the condition involves drugs that provide immediate pain relief.

Regulatory bodies recommend non-steroidal anti-inflammatory medicines (NSAIDs) for first-line therapy, with triptans reserved for moderate and severe attacks or inadequate responses. Patients contraindicated for triptan use due to probable vasoconstrictive effects or those at high risk of cardiovascular disease might prefer recently marketed drugs such as lasmiditan and gepants. However, there is no universal consensus on the ranking of drugs to treat migraine.

About the study

The present meta-analysis provides comprehensive information on drugs used to manage acute episodes of migraine 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. Researchers also searched the websites of pharmaceutical companies and regulatory agencies without language limitations through June 24, 2023.

The included studies were double-blinded randomized controlled trials (RCTs) evaluating orally administered drugs as monotherapy for migraine compared to placebo or other active therapeutic to manage acute episodes of migraine among adults. They did not investigate opiate use and did not conduct evaluations in emergency departments. Migraine diagnosis followed the International Classification of Headache Disorders (ICHD) criteria. International regulatory bodies recommend these drugs for migraine.

Two independent researchers screened and extracted data. Discussions with team members resolved disagreements between them. The second version of the Cochrane risk of bias tool (RoB2) indicated bias risk in the included studies. The confidence in network meta-analysis (CINeMA) tool graded the certainty of evidence.

The primary study outcomes included the percentage of pain-free individuals two hours after drug consumption and those with freedom from pain two hours to a day after taking the dose without using rescue drugs. The secondary outcomes were relief from pain two hours after drug consumption, pain relapse in two hours to two days, and rescue drug use two hours to 24 hours after the intervention. Other outcomes included the tolerability and safety of the drug interventions.

Random effects network meta-analyses analyzed primary data. Odds ratios (ORs) indicated treatment effect sizes. Researchers involved public input and feedback from migraine sufferers. They presented the results to expert clinicians and patient representatives from international organizations across Argentina, Canada, Europe, and the United States (US).

Results

The meta-analysis included 137 RCTs, including 89,445 individuals, among whom the mean age was 40 years; 86% were female, and 32% experienced migraine with aura. The certainty of the evidence ranged from high to very low. The risk of bias was low for pain freedom evaluation in 21% and high in 16% of RCTs. For sustained pain freedom, the risk of bias was low in 29% and high in 11% of RCTs.

All therapies were more effective than placebo for relief from pain after two hours (OR ranging between 1.7 for naratriptan and 5.2 for eletriptan). Most interventions also showed higher efficacy in relieving pain for 24 hours (OR ranging between 1.7 for celecoxib and 7.6 for ibuprofen). Eletriptan showed the highest efficacy for two-hour pain freedom (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 the most effective for long-term freedom from pain (OR 1.4 to 4.8).

All interventions performed better than placebo for pain relief at two hours and rescue drugs from two to 24 hours. Eletriptan was the most effective for pain relief at two hours (OR from 1.3 to 2.6) and compared to rescue drugs (OR from 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, paraesthesia, and sedation after lasmiditan use.

The team obtained similar results in the sensitivity analyses, including only United States Food and Drug Administration (FDA)-approved doses and studies with low bias. The participants of these trials experienced moderate or severe headaches, had no comorbidities, and did not use preventive drugs.

Conclusion

The findings showed that triptans, including rizatriptan, eletriptan, zolmitriptan, and sumatriptan, were the most effective and tolerable drugs for the acute management of migraine among adults. These drugs are more effective than recently marketed ones (Ubrogepant, lasmiditan, and rimegepant), which showed efficacy comparable to NSAIDs. Including high-efficacy triptans in WHO’s Essential Medicines List could improve global access and care. Cost-effective analyses are warranted to inform clinical decision-making.