Migraine prevention: which medicines work, according to a review of 217 trials

For many people with migraine, the goal is not just to stop an attack but to have fewer of them. There are more ways to do that than ever, from monthly antibody shots to pills that have been around for decades. Choosing between them can feel like guesswork.

The American Academy of Neurology and the American Headache Society have updated their guidance. The systematic review behind it, published in Neurology, weighed 217 randomized trials and graded how confident the evidence is for each medicine.

What migraine is and why prevention matters

MedlinePlus describes migraines as a recurring type of headache and notes that about 12% of Americans get migraines, with women about three times as likely as men to be affected. Attacks can bring severe pain, nausea and sensitivity to light and sound.

Preventive medicines are taken regularly to cut the number and severity of attacks, rather than to treat one once it starts. As the review puts it, its purpose was to provide updated evidence-based conclusions regarding the use of pharmacologic migraine prevention in adults for the new joint guideline.

How the migraine review worked

A panel of experts searched for randomized trials of preventive medicines in adults with migraine, up to June 2024. In all, a total of 217 studies met inclusion criteria.

The panel looked at monthly headache days, the share of people whose headaches were cut by half or more, and quality of life. It then graded how sure it could be of each finding: high, moderate, low or very low.

Which migraine medicines had the strongest evidence

For episodic migraine, the review found high-confidence evidence that galcanezumab and erenumab are more effective than placebo at reducing how often headaches happen. Both are antibodies that block CGRP (calcitonin gene-related peptide), a signaling molecule involved in migraine attacks. Moderate-confidence evidence supported the related drugs atogepant, eptinezumab and fremanezumab, and three long-used pills: propranolol, topiramate and valproate.

For chronic migraine, the strongest evidence was for fremanezumab, galcanezumab and onabotulinumtoxinA, better known as Botox injections. Several older tablets, including amitriptyline, had lower-confidence evidence suggesting possible benefit. A number of the drugs also improved quality of life on validated questionnaires.

Why the new migraine guidance matters

The review confirms that both newer targeted treatments and older, cheaper tablets can reduce headache days, which widens the realistic choices. The companion guideline adds practical advice on how to decide when it is appropriate to start a preventive medicine, how to choose among options, and how to handle situations such as obesity, high blood pressure, older age, pregnancy and breastfeeding, and medication overuse.

That matters because the best drug for one person may be a poor fit for another. Topiramate and valproate carry risks in pregnancy, for example. Propranolol may suit someone who also has high blood pressure.

What a migraine review cannot settle

The review found that evidence comparing active treatments was limited and generally of low or very low confidence. Most trials compared a drug with placebo, not with another drug, so it cannot say which medicine works best overall.

The search ended in June 2024, so newer trials are missing. People in trials may differ from people seen in clinics. And cost, insurance and side effects shape real choices in ways a review like this cannot capture.

What this changes for people with migraine

For people with frequent or disabling migraine, the review is a reminder that prevention works for many and that there is more than one route. If one medicine fails or causes side effects, there are others with good evidence.

The practical step is a conversation with a doctor about attack frequency, other health conditions and plans such as pregnancy, and a clear way to judge after a few months whether a preventive medicine is helping.