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Chronic migraine can be difficult to treat—but new research is helping identify the most effective options. In a large new review, published in the Annals of Internal Medicine, researchers analyzed 43 clinical trials involving adults with chronic migraine, defined as headaches on 15 or more days a month.
The strongest evidence pointed to a newer class of medications called CGRP-targeted therapies, according to the results. These drugs were shown to reduce monthly migraine days by about two and were generally well tolerated. Examples of CGRP-targeted therapies include eptinezumab (brand name, Vyepti) and atogepant (Qulipta).
CGRP is a protein found in the brain and nervous system that spikes during migraines, triggering pain and inflammation. The drugs are designed to block that process.
Available as shots, infusions, pills and a nasal spray, the drugs were also found to have fewer side effects than older treatments.
By comparison, the evidence showed botulinum toxin, or Botox, may offer some benefit but with less certainty and more side effects, leading to treatment drop-off.
For older medications like topiramate, valproate and propranolol, the evidence was also limited and even less reliable.
The researchers say more independent studies on CGRP therapies are needed, especially on long-term safety and adherence.
They add that while newer therapies appear to show the most promise, the right treatment depends on a patient’s individual needs and preferences, as well as cost. They recommend talking with your health care provider to find the best option.
Malahat Khalili of the Michael G. DeGroote Institute for Pain Research and Care at McMaster University in Hamilton, Ontario, Canada, led the study.
Publication details
Malahat Khalili et al, Effectiveness and Tolerability of Pharmacologic Prophylaxis for Chronic Migraine, Annals of Internal Medicine (2026). DOI: 10.7326/annals-25-02221
Journal information:
Annals of Internal Medicine
Key medical concepts
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Newer migraine drugs reduce headache days with fewer side effects (2026, May 5)
retrieved 6 May 2026
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