Triptans Prove to be More Effective for Migraines Than Newer Drugs

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The drugs eletriptan, rizatriptan, sumatriptan, and zolmitriptan are more effective at treating acute migraines than newer, more expensive drugs, a new study revealed.^1,2

“These four triptans were more efficacious than the most recently marketed drugs lasmiditan, rimegepant, and ubrogepant, which, based on our results, showed efficacy comparable to that of paracetamol and most NSAIDs,” wrote investigators, led by William K Karlsson, from Copenhagen University Hospital in Dennmark.

More than a billion people worldwide experience migraines, and this is the leading cause of disability in females aged 15 – 49 years. Migraine medication exists, but as of now, there is no consensus on what drugs perform the best.

Triptans have low acquisition costs and balanced efficacy and tolerability profiles but remain underused among individuals who get migraines. In the US, 16.8% - 22.7% use triptans. Despite the effectiveness of triptans for migraines, patients with vascular disease should not take them.

Sometimes, cerebrovascular events can appear as migraine-like headaches. This leads to the misdiagnosis of transient ischemic attacks and minor strokes as migraines.

Research has shown that high doses of intravenous eletriptan or subcutaneous sumatriptan had no clinically significant vasoconstriction in patients undergoing diagnostic coronary angiography. New drugs, such as lasmiditan, rimegepant, and ubrogepant, are not associated with vasoconstrictive effects and thus advertised as alternatives for patients who cannot take triptans.

Investigators conducted a systematic review and network meta-analysis to compare the effectiveness of all licensed drug interventions as oral monotherapy for treating acute migraines in adults. The primary outcomes were the number of pain-free participants 2 hours after the dose and the number of participants with sustained pain alleviation up to 24 hours after the dose without using rescue drugs.

The team leveraged data from Cochrane Central Register of Controlled Trials, Medline, Embase, ClinicalTrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, and websites of regulatory agencies and pharmaceutical companies without language restrictions until June 24, 2023. Ultimately, the study included 137 double-blind randomized trials of adults ≥ 18 years old with a diagnosis of migraine based on the International Classification of Headache Disorders. Among the 89,445 participants, 85.6% were female and the mean age was 40.3 years.

Participants on a triptan demonstrated superior pain alleviation compared with those on a placebo at 2 hours. The superior efficacy was seen for participants on naratriptan (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.27 – 2.35) and eletriptan (OR, 5.19; 95% CI< 4.25 – 6.33). Participants on celecoxib (OR, 1.71; 95% CI, 1.07 – 2.74) and ibuprofen (OR, 7.58; 95% CI, 2.58 – 22.27) also had sustained pain relief.

When evaluating head-to-head comparisons between active interventions, the team discovered eletriptan was the most effective drug for relieving pain at 2 hours (from OR, 1.46; 95% CI, 1.18 – 1.81) to 3.01 (95% CI, 2.13 – 4.25), followed by rizatriptan (from OR,1.59; 1.18 – 2.17) to 2.44 (95% CI, 1.75 – 3.45), sumatriptan (from OR, 1.35; 1.03 – 1.75) to (OR, 2.04; 95% CI, 1.49 – 2.86), and zolmitriptan (OR, 1.47; 1.04 – 2.08) to (OR, 1.96; 95% CI, 1.39 – 2.86).

“Celecoxib ranked lowest among NSAIDs, whereas sparse evidence was available for phenazone,” investigators wrote.

For pain relief sustained for 24 hours, the most effective interventions were eletriptan and ibuprofen (from OR 1.41; 95% CI, 1.02 – 1.93) to (OR, 4.82; 95% CI, 1.31 – 17.67).

Investigators recommended that certain triptans—eletriptan, rizatriptan, sumatriptan, and zolmitriptan—should be considered first-line treatments for migraines. They also suggested that ibuprofen, acetylsalicylic acid, diclofenac potassium, almotriptan, and frovatriptan should be used as second-line treatments. They also wrote how the newer and more expensive drugs—lasmiditan, rimegepant, and ubrogepant—should be reserved for third-line options.

“Taken together, NSAIDs performed worse than triptans, were comparable to gepants, and were less likely to cause adverse events compared with lasmiditan,” investigators wrote. “Paracetamol, although showing limited effect for pain freedom at two hours, proved to be well tolerated, affirming its role as a viable option for those seeking pain relief with low risk of adverse events.”

References

1. ^{Karlsson WK, Ostinelli EG, Zhuang ZA, et al. Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis. BMJ. 2024;386:e080107. Published 2024 Sep 18. doi:10.1136/bmj-2024-080107}
2. ^{Triptans more effective than newer, more expensive migraine drugs. EurekAlert! September 18, 2024. https://www.eurekalert.org/news-releases/1058120. Accessed October 3, 2024.}