Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine

Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine
Hailey Haugen, PharmD, CentraCare Health - St. Cloud

Background: Triptans, or 5-hydroxytryptamine1B/1D (5-HT1B/1D) receptor agonists, are widely regarded as the standard of care for the treatment of acute migraine. However, there are concerns with the efficacy and high discontinuation rate of these agents. Frequent use of triptans may also lead to medication overuse headaches. Additionally, these agents are contraindicated in patients with high cardiovascular risk due to their mechanism of inducing vasoconstriction. Two new classes of migraine drugs have been developed to provide improved outcomes for patients in whom triptans are either ineffective or unsafe. These two classes are the ditans, which are 5-hydroxytryptamine1F (5-HT1F) agonists and the gepants, which are calcitonin gene-related peptide (CGRP) antagonists. Limited information is available regarding the efficacy and safety of these newer agents compared to the standard of care for migraine treatment.

Purpose: To compare the benefits and adverse effects of triptans with newer agents 5-HT1F agonists (lasmiditan) and CGRP antagonists (rimegepant, ubrogepant) for the treatment of acute migraine attacks.

Study Design: This was a systematic review and meta-analysis that included double-blind randomized clinical trials (RCTs) with participants 18 years or older, reviewed currently available acute treatments for migraine at doses widespread in clinical use, had comparisons between specific therapies and/or placebo, and used the International Headache Society criteria for migraine diagnosis. Articles were excluded if they compared the same medication using different routes of administration. The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from the databases’ inception to March 5, 2020. A total of 261 articles were considered and 64 trials met inclusion criteria. The primary outcome was freedom from pain two hours after treatment. The secondary outcomes were pain relief two hours after treatment and tolerability determined by the number of adverse effects. For each specified outcome, the odds ratio (OR) was estimated with 95% CI using random-effects models.

Results: A total of 64 RCTs were included with 46,442 patients aged 36-43 years old and included 74-87% females. Triptans had a higher rate of pain freedom at two hours compared with 5-HT1F agonist, lasmiditan (range: OR, 1.72 [95% CI, 1.06-2.80] to OR, 3.40 [95% CI, 2.12-5.44]). Triptans also had a higher rate of pain freedom compared with CGRP antagonists, 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]). Triptans were associated with significantly better pain relief at two hours compared to lasmiditan, rimegepant, or ubrogepant. Lasmiditan had the highest OR of any adverse events compared to placebo. Triptans such as rizatriptan, sumatriptan, and zolmitriptan were associated with a higher OR of adverse events than the CGRP antagonists. Specifically, triptans had a higher OR of chest symptoms in all adverse events including chest pain, tightness, heaviness, and pressure compared to CGRP antagonists. Most patient reported adverse events were mild to moderate and were considered tolerable.

Conclusion: Newer agents lasmiditan, rimegepant, and ubrogepant were associated with lower ORs for pain freedom and pain relief at 2 hours post dose compared to most triptans. However, there still may be a benefit of these newer agents for patients who have failed triptans or have cardiovascular contraindications. A key limitation of the study is the focus on short-term efficacy and safety after a single dose for a single migraine attack rather than long-term use when used for repeated migraine attacks. This study also did not specify the types of adverse events, and instead compared the overall rates of adverse events from each study included in the meta analysis.

Key Point: Triptans were shown to be more effective for pain freedom and pain relief at 2 hours post dose compared to newer agents lasmiditan, rimegepant, and ubrogepant. The benefits of the newer agents may be found in their use for repeated migraine attacks, and for patients who have failed, had adverse effects, or have contraindications to triptan use.


  1. 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 Network Open. 2021;4(10):e2128544-e2128544. doi:10.1001/JAMANETWORKOPEN.2021.28544