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Research Headache & Migraine Pain
Review of 217 Trials Rates Evidence for Migraine Prevention Drugs
A systematic review that informs a new AAN and American Headache Society guideline grades how strong the evidence is for each preventive migraine medicine in adults.
Reporting on an item first published by pubmed.ncbi.nlm.nih.gov. See Sources.
This article is general health information written by our editors from the sources listed below. It has not yet been medically reviewed — see our medical review policy. It is not advice for your situation.
If you live with frequent migraine, you may have tried a preventive medicine, the kind taken regularly to make attacks less frequent rather than to stop one in progress. A large systematic review published in Neurology has now sorted these drugs by how much trust can be placed in the research behind them.
The review drew on 217 randomized trials and was written to inform a new joint guideline from the American Academy of Neurology and the American Headache Society. It may give patients and clinicians a clearer view of which medicines have the firmest backing. It also shows how little is known about how these drugs compare with each other.
Episodic migraine: two drugs earn the top confidence rating
For episodic migraine, the researchers found high-confidence evidence for two medications, galcanezumab and erenumab, which lowered headache frequency more than a placebo, or dummy treatment. In rating systems like this one, a high rating usually suggests that more research may be unlikely to change the conclusion much.
Six other drugs had moderate-confidence evidence of benefit in episodic migraine. A longer list of oral medicines had only low-confidence evidence, which hints at possible benefit but leaves real room for doubt.
- High confidence: galcanezumab, erenumab
- Moderate confidence: atogepant, eptinezumab, fremanezumab, propranolol, topiramate, valproate
- Low confidence, possible benefit: amitriptyline, bisoprolol, flunarizine, fluoxetine, levetiracetam, metoprolol, nifedipine, pizotifen, telmisartan
Chronic migraine: a different set of top-rated treatments
The picture shifted for chronic migraine. Here, fremanezumab, galcanezumab and onabotulinumtoxinA had high-confidence evidence for cutting how often headaches occur. Atogepant, eptinezumab, erenumab, topiramate and valproate were supported by moderate-confidence evidence.
Some drugs sat in different tiers depending on the type of migraine. Erenumab was rated high confidence for episodic migraine but moderate for chronic migraine, while fremanezumab moved the opposite way. This could reflect how much trial data exists for each group rather than how well a drug works, but the abstract does not explain it.
- High confidence: fremanezumab, galcanezumab, onabotulinumtoxinA
- Moderate confidence: atogepant, eptinezumab, erenumab, topiramate, valproate
Quality of life, not just headache counts
The researchers tracked three kinds of results: the change in headache days per month, the share of people whose headaches dropped by at least 50%, and quality of life measured with validated questionnaires that patients complete themselves.
Eight treatments showed quality-of-life gains across both episodic and chronic migraine: erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, atogepant, topiramate and onabotulinumtoxinA. For many people, how they feel and function day to day may matter as much as the number of headache days, so these results could be useful when discussing options.
How the researchers weighed the evidence
The team included only randomized controlled trials, in which people are assigned by chance to a treatment or a comparison, testing preventive medicines in adults with either episodic or chronic migraine. They searched MEDLINE, Embase and ClinicalTrials.gov from the earliest available records up to June 6, 2024.
Two reviewers screened every study, and two people independently judged each trial's risk of bias, meaning the chance that flaws in its design skewed the results. Certainty was then graded using a modified version of GRADE, a method for rating how much confidence a body of evidence deserves.
What the evidence does and does not show
The biggest gap is in head-to-head comparisons. Few trials pitted one active drug against another, and that evidence was mostly rated low or very low confidence, so the review cannot say which medicine works best. The top-rated findings for episodic migraine came from comparisons with placebo.
Only the abstract of the review was available for this article, which leaves several questions open.
- The abstract does not report effect sizes, such as how many headache days each drug removed on average or what share of people responded.
- Side effects and safety are not described in the abstract.
- Funding and conflicts of interest are not stated in the source.
- Trials published after June 6, 2024, are not included.
- A confidence rating describes the strength of the evidence, not how well a drug will work for any one person.
What this may mean for people living with migraine
The review's conclusions were used to develop recommendations to help clinicians choose preventive medicines, and those appear in a separate companion paper. This article covers only the evidence review, not what the guideline advises clinicians to try first.
If migraine is disrupting your work, sleep or family life, or your headache pattern has changed, it may be worth raising prevention with a clinician. The right choice can depend on your migraine pattern, other health conditions, other medicines you take and possible side effects, which the abstract does not address.
Pain specialists, such as those at SEVA Healthcare, evaluate headache and migraine and can talk through the options with you. Please do not start, stop or change any medication based on this article; those decisions belong with a qualified clinician who knows your history.
Frequently asked questions
Which migraine prevention drugs had the strongest evidence in this review?
For episodic migraine, galcanezumab and erenumab had high-confidence evidence of reducing headache frequency compared with placebo. For chronic migraine, fremanezumab, galcanezumab and onabotulinumtoxinA had high-confidence evidence.
Does the review say which preventive drug works best?
No. Few studies compared active treatments directly, and that evidence was generally low or very low confidence, which limits any conclusion about which drug is most effective.
Is this review the new migraine guideline?
Not exactly. The review was written to inform a joint AAN and American Headache Society guideline, and the recommendations themselves appear in a separate companion publication.
Did the review look at side effects?
The abstract available for this article does not describe side effects or safety, so it cannot tell us how well each drug is tolerated. A clinician can discuss possible side effects for your situation.
Should I ask about changing my migraine medicine because of this review?
This review describes evidence across groups of people, not what is right for you. If your migraines are not well controlled, talk with a qualified clinician, such as a pain or headache specialist, before making any change.
Sources
This article is sponsored content by SEVA and is for general information only — it is not medical or legal advice. Treatment options depend on an individual evaluation, and results vary from person to person. In an emergency, call 911. Spotted an error? See our corrections policy.
