New Drugs for Migraine Symptoms Are Not Always More Effective Than Old Ones, Study Finds

Migraine is a common neurological condition that can cause debilitating, recurrent headaches, which can last several hours and up to a few days. Migraine headaches often occur together with other symptoms, such as vision changes, nausea, and sensitivity to sounds or light.[1],[2]

Although there is no cure for migraines, symptoms can often be managed through lifestyle changes, such as avoiding or mitigating triggers that can bring on headaches for some patients.[3] Common triggers include changes in sleep routines, stress, hormonal changes, skipping meals, or various foods or drinks. Over-the-counter and prescription drugs are also available.

A systematic review and network meta-analysis published in The BMJ[4] in September 2024 compared the efficacy and tolerability of several oral migraine drugs and found that some older drugs perform as well as or better than newer, more expensive drugs. A network meta-analysis is a statistical technique that allows for the comparison of multiple drugs for a medical condition, even when the drugs have not been directly compared with each other in a study. The results of a network meta-analysis, however, can be susceptible to bias and must be carefully analyzed.

Medications for migraine symptoms

For mild to moderate migraine attacks, over-the-counter drugs such as acetaminophen (TYLENOL and generics; also known as paracetamol) and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (ADVIL, MIDOL, MOTRIN and generics) are generally recommended as a first treatment.[5],[6] If these drugs do not adequately reduce pain, prescription medications can be considered.[7] The BMJ study included 17 different drugs from five drug classes, including acetaminophen, NSAIDs, and three classes of prescription migraine drugs:[8] triptans, ditans and gepants. The study did not include drugs that are only approved to prevent or reduce the frequency of migraine attacks. The study also did not include opioids. Opioids should not be used to treat or prevent migraines, due to their risk of addiction and limited efficacy.[9]

Triptans

Between 1992 and 2002 the Food and Drug Administration (FDA) approved seven triptans: almotriptan (generic only), eletriptan (RELPAX and generics), frovatriptan (FROVA and generics), naratriptan (generic only), rizatriptan (MAXALT and generics), sumatriptan (IMITREX and generics) and zolmitriptan (generic only).[10] All seven triptans were included in the study.

Triptans (also known as serotonin receptor agonists) are associated with several serious adverse events, such as heart attacks or other heart problems, chest pain or pressure, abnormal heart rhythms, and medication overuse headache (an exacerbation of the headaches caused by the overuse of triptans and other drugs used to treat migraines).[11],[12] For this reason, Public Citizen’s Health Research Group has designated all triptans as Limited Use and recommends these drugs only be considered if acetaminophen and NSAIDs have failed to provide relief.

One of the main concerns with triptans is that they cause blood vessels in the brain and heart to tighten (vasoconstriction).[13],[14] Because of this effect, these drugs are not recommended for patients with heart conditions, a history of heart problems, or uncontrolled hypertension (high blood pressure).

Ditans and gepants are newer drug classes for the treatment of acute migraines. The study included only some of the ditans and gepants approved in the United States. These drugs do not have vasoconstrictive effects and have been marketed as an alternative for patients who cannot take triptans.[15] Public Citizen’s Health Research Group has not reviewed ditans or gepants.

Ditans

The study included lasmiditan (REYVOW), a selective serotonin receptor agonist that the FDA approved in 2020.[16] Lasmiditan is associated with serious adverse events including serotonin syndrome (which can include hallucinations, irregular or fast heartbeat, and trouble walking) and medication overuse headache.

Gepants

Gepants are calcitonin gene-related peptide receptor antagonists. The study included ubrogepant (UBRELVY),[17] which the FDA approved in 2019 to treat migraine symptoms, and rimegepant (NURTEC ODT), which the FDA approved in 2020[18] to treat migraine symptoms and to prevent migraine attacks. Gepants are associated with serious adverse effects, including allergic reactions that can lead to difficulty breathing and swelling of the mouth, throat and face.

The results of the new study

The BMJ study included 137 randomized, double-blind clinical trials involving 17 drugs that collectively enrolled nearly 90,000 adults.[19] Subjects were, on average, 40 years of age; the majority were women (86%), and about one-third had a history of migraine with aura. The researchers assessed the safety and tolerability of different migraine treatments, as well as whether and for how long migraine drugs stopped or reduced migraine pain compared with placebo.

Overall, the study found that all included drugs performed better than placebo to stop or reduce pain.[20] Moreover, the results indicated that triptans, especially eletriptan, rizatriptan, sumatriptan and zolmitriptan, had the best efficacy and safety profile. The efficacy of the newer drugs lasmiditan, rimegepant and ubrogepant was found to be comparable to that of acetaminophen and several NSAIDs.

Importantly, all migraine drugs, particularly lasmiditan, were associated with adverse events, such as dizziness, tingling or burning sensation on the skin (paraesthesia), nausea, fatigue, and sedation.[21] Chest pain or discomfort, however, was mainly associated with eletriptan. Although acetaminophen was associated with the lowest risk of adverse events, it was found to have a more limited effect on stopping migraine pain than triptans.

The study only included trials that each compared one migraine drug with placebo. The study did not include trials with head-to-head comparisons between the different classes of migraine drugs, such as triptans and gepants; this may limit the generalizability of the study results.

What You Can Do

If you have migraines, try to identify triggers by keeping a journal and try to reduce migraine attacks through lifestyle changes. To relieve acute migraine symptoms, try acetaminophen or NSAIDs first. If these drugs do not adequately relieve pain, discuss with your clinician whether triptans (which are discussed in more detail in the June 2023 issue of Worst Pills, Best Pills News) or another class of drugs are a good option for you.
 

References

[1] Cleveland Clinic. Migraine headaches. Reviewed January 23, 2024. https://my.clevelandclinic.org/health/diseases/5005-migraine-headaches. Accessed November 25, 2024.

[2] Lifestyle treatments to prevent or reduce the frequency of migraine headaches. Worst Pills, Best Pills News. November 2023. https://www.worstpills.org/newsletters/view/1564. Accessed November 25, 2024.

[3] Cleveland Clinic. Migraine headaches. Reviewed January 23, 2024. https://my.clevelandclinic.org/health/diseases/5005-migraine-headaches. Accessed November 25, 2024.

[4] 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(September 18):e080107.

[5] Lifestyle treatments to prevent or reduce the frequency of migraine headaches. Worst Pills, Best Pills News. November 2023. https://www.worstpills.org/newsletters/view/1564. Accessed November 25, 2024.

[6] 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(September 18):e080107.

[7] Review of the triptan drugs for treating migraines. Worst Pills, Best Pills News. June 2022. https://www.worstpills.org/newsletters/view/1468. Accessed November 25, 2024.

[8] 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(September 18):e080107.

[9] 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(September 18):e080107.

[10] Review of the triptan drugs for treating migraines. Worst Pills, Best Pills News. June 2022. https://www.worstpills.org/newsletters/view/1468. Accessed November 25, 2024.

[11] Ibid.

[12] Drug profile. Triptans. Last reviewed August 31, 2024. https://www.worstpills.org/monographs/view/50. Accessed November 25, 2024.

[13] Review of the triptan drugs for treating migraines. Worst Pills, Best Pills News. June 2022. https://www.worstpills.org/newsletters/view/1468. Accessed November 25, 2024.

[14] Vu M, Jarrett TL, Newsom LC. Consider cardiovascular risk factors before prescribing triptans for migraine. Am Fam Physician. 2018;98(6):342.

[15] 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(September 18):e080107.

[16] Eli Lilly. Label: lasmiditan (REYVOW). September 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/211280s008lbl.pdf. Accessed November 25, 2024.

[17] Allergan. Label: ubrogepant (UBRELVY). February 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/211765s007lbl.pdf. Accessed November 25, 2024.

[18] Biohaven. Label: rimegepant (NURTEC ODT). April 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212728s009lbl.pdf. Accessed November 25, 2024.

[19] Ibid.

[20] Ibid.

[21] Ibid.