Newer Pharmacotherapies Compared With Triptans for Migraine Treatment

The analysis included 64 randomized clinical trials with a total of 46,442 patients.

Newer migraine pharmacotherapies appear to be less effective than triptans, according to findings from a systematic review and meta-analysis published in JAMA Network Open.

Newer medication classes include the 5-hydroxytryptamine1F receptor agonists (lasmiditan) and the calcitonin gene-related peptide antagonists (rimegepant, ubrogepant). The study authors aimed to compare outcomes associated with the use of these agents vs triptans in the acute management of migraine headaches.

Double-blinded randomized clinical trials analyzing available migraine-specific acute therapies were obtained by searching the Cochrane Register of Controlled Trials, Embase, and PubMed from inception to March 5, 2020. The primary endpoint of the analysis was the odds ratio (OR) for freedom from pain (“pain freedom”) at 2 hours following the dose and secondary endpoints included ORs for pain relief at 2 hours post dose as well as any adverse events.

The analysis included 64 randomized clinical trials with a total of 46,442 patients. The age range of the patients was reported to be 36 to 43 years and 74% to 87% of the population was female.

Findings showed that compared with placebo, the majority of therapies included in the analysis were associated with reduced pain at 2 hours following the dose.

“Most triptans were associated with higher ORs for pain freedom at 2 hours compared with lasmiditan (range: OR, 1.72 [95% CI, 1.06-2.80] to OR, 3.40 [95% CI, 2.12-5.44]), rimegepant (range: OR, 1.58 [95% CI, 1.07-2.33] to OR, 3.13 [95% CI, 2.16-4.52]), and ubrogepant (range: OR, 1.54 [95%CI, 1.00-2.37] to OR, 3.05 [95% CI, 2.02-4.60]),” the study authors reported.

Findings also showed that triptans were more effective in providing pain relief at 2 hours compared with lasmiditan (range: OR, 1.46 [95% CI, 1.09-1.96] to OR, 3.31 [95% CI, 2.41-4.55]), rimegepant (range: OR, 1.33 [95% CI, 1.01-1.76] to OR, 3.01 [95% CI, 2.33-3.88]), and ubrogepant (range: OR, 1.38 [95% CI, 1.02-1.88] to OR, 3.13 [95% CI, 2.35-4.15]).

Among all the treatments, lasmiditan was found to carry the greatest risk for adverse events. Compared with rimegepant and ubrogepant, rizatriptan, sumatriptan, and zolmitriptan were all associated with a higher risk for adverse events.

While more effective than placebo, lasmiditan, rimegepant, and ubrogepant were all associated with lower ORs for pain freedom and pain relief at 2 hours post dose compared with most triptans. “However, the lack of cardiovascular risks of these new classes of migraine-specific treatments may provide alternative treatment options for individuals for whom currently available acute treatments have failed or for those with cardiovascular contraindications,” the authors concluded.

Disclosure: Some study authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.


Yang CP, Liang CS, Chang CM, 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.