Newer Drugs vs Triptans for Pain Relief in Migraine Headaches

New classes of migraine medications had lower cardiovascular risk than triptans and may be a suitable alternative for patients with cardiovascular contraindications. These findings, from a systematic review and meta-analysis, were published in JAMA Network Open.

In recent years, new classes of migraine-specific medications, 5-hydroxytryptamine receptor agonists (lasmiditan) and calcitonin gene-related peptide (CGRP) antagonists (ubrogepant and rimegepant) have been developed. Due to their novelty, it remains unclear how they compare with the established migraine medications, triptans.

Publications databases were searched through March 2020 for double-blind randomized clinical trials of migraine-specific acute treatments. A total of 62 articles met the inclusion criteria.

The study population comprised of 46,442 patients aged between 36 and 43 years and 74%-87% were women. Most studies (92%) allowed for concurrent use of preventative medications.

Compared with placebo, 50 mg lasmiditan had the lowest efficacy for freedom from pain at 2 hours (odds ratio [OR], 1.65; 95% CI, 1.08-2.50) and 40 mg eletriptan had the highest (OR, 5.59; 95% CI, 4.50-6.94). Most triptans had higher efficacy than lasmiditan (OR range, 1.72-3.40), rimegepant (OR range, 1.58-3.13), and ubrogepant (OR range, 1.54-3.05). The comparisons between lasmiditan, rimegepant, and ubrogepant were not significant.

Adverse events were highest for 400 mg lasmiditan (OR, 9.66; 95% CI, 4.03-23.16). There was a dose-response relationship between adverse events and eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan. Triptans had higher risk for adverse events than rizatriptan (OR, 1.96; 95% CI, 1.14-3.35), sumatriptan (OR, 1.83; 95% CI, 1.09-3.09), or zolmitriptan (OR, 2.34; 95% CI, 1.39-3.95). Chest pain, tightness, heaviness, and pressure accounted for 0%-20% of adverse events.

After removing studies with high risk for bias, lasmiditan had a lower risk for adverse events and CGRP antagonists had higher efficacy for 2-hour pain relief.

This study was limited by focusing on short-term headache relief and adverse events after a single dose. Long-term pain relief and exposure risk were not considered.

The study authors concluded that triptans tended to have higher pain relief efficacy than newer pharmacologic agents for migraine, but were associated with increased risk for adverse events, including chest symptoms. They concluded “the lack of cardiovascular risks for these new classes of migraine-specific treatments may offer an alternative to triptans.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Yang C-P, Liang C-S, Chang C-M, et al. Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine: A Systematic Review and Meta-analysis. JAMA Netw Open. Published online October 11, 2021. doi:10.1001/jamanetworkopen.2021.28544