This is a plain English summary of an original research article. The views expressed are those of the author(s) and reviewer(s) at the time of publication.
People with chronic migraine (attacks on 15 or more days per month) may need prescription drugs to help them manage their condition. Researchers analysed studies on drugs to prevent migraine attacks.
They found that:
- all drugs tested reduced the number of days people had headaches and migraine attacks
- newer drugs (for instance, eptinezumab and erenumab) were more effective than traditional ones (such as topiramate)
- traditional drugs were cheaper but had more adverse events than newer ones.
The findings add to existing knowledge about which preventive treatments are most effective for people with chronic migraine.
More information about migraine can be found on the NHS website.
Which drugs prevent migraine attacks?
Migraines feel like severe headaches, often with throbbing pain on one side; other symptoms may include nausea, blurred vision and a need to rest. Around 2 in 100 people in the UK have chronic migraine. The condition can be disabling, lead to time off work and reduced quality of life. Treatments (including triptans) are available for migraine attacks when they occur, but they are not suitable for regular use.
Preventive drugs can reduce the impact of chronic migraine. Most of the newer drugs can be prescribed only by a specialist (neurologist); some can be prescribed by GPs (or GPs can continue prescribing drugs started by a specialist). Several drugs are recommended by the National Institute for Health and Care Excellence (NICE). But the evidence is mixed and it is unclear which is the most effective.
Newer drugs (eptinezumab, erenumab, fremanezumab and galcanezumab), usually given by monthly injection, are reserved for people in whom 3 previous treatments have failed. Researchers compared the effectiveness of medications, including newer treatments, for people with chronic migraine. All of the drugs in the report are approved by NICE.
What’s new?
The researchers looked at 12 trials involving 7,909 people in all; each trial included 200 or more adults with chronic migraine. Most trials compared a preventive drug with a dummy drug (placebo). There were no eligible trials of commonly-used preventive drugs, such as amitriptyline or propranolol.
In 8 trials (of eptinezumab, erenumab, fremanezumab, galcanezumab, botulinum toxin A, and topiramate), all drugs reduced the number of days with headache (rather than a migraine attack). They found:
- the most effective was eptinezumab 300mg (which reduced the number of days with headache by 2.5 per month more than placebo)
- the least effective was topiramate 100mg (which reduced the number of days with headache by 1.1 per month more than placebo).
In 11 trials of the same drugs, all reduced the number of days with a migraine attack. They found:
- the most effective was monthly fremanezumab (which reduced the number of days with a migraine attack by 2.8 per month more than placebo)
- the least effective was topiramate 100mg (which reduced the number of days with a migraine attack by 1.5 per month more than placebo).
In 10 trials, all drugs apart from topiramate, were more effective than placebo at improving headache-related quality of life. Headache-related quality of life assesses the extent of someone’s pain or discomfort, and how often headaches limit their daily activities.
The same team reviewed 33 studies on the adverse events of 10 drugs. They found that amitriptyline and topiramate were linked with the most adverse events, especially relating to the nervous system (tingling or numbness of the skin, for example). Newer treatments had fewer adverse events.
On price, topiramate was the only drug within the limit set by NICE (£30,000 per year of good health). However, topiramate gave only slightly more years of good health (QALYs) than a dummy pill (placebo). In addition, girls or women who could become pregnant need long-acting contraception (such as the coil or implant) before they are prescribed topiramate. Eptinezumab was the most expensive treatment but gave the largest increase in years in good health.
Why is this important?
Migraine drugs effectively reduced the number of days people had headaches or migraine attacks in this study. They also improved quality of life. Differences between drugs were modest, the researchers say.
The effectiveness study did not include other drugs used to prevent migraine attacks in England and Scotland (amitriptyline, propranolol, candesartan or flunarizine) because of limitations in the evidence.
Nearly all studies compared drugs with placebo; this means the findings do not compare drugs directly with one another. Therefore, conclusions about the most and least effective drugs need to be treated with caution. Most trials in this analysis included participants with and without medication overuse, which could have made the preventive treatments appear less effective than they really are.
What’s next?
More research is needed to determine the effectiveness and value for money of traditional, cheaper, preventive drugs for people with chronic migraine. The adverse events related to newer and traditional drugs also need to be compared, the researchers say. At a consensus workshop run by the research team, participants prioritised comparison of 2 treatments (calcitonin gene-related peptide monoclonal antibodies, and botulinum toxin A). Candesartan and flunarizine were the drugs the group most wanted to see compared with placebo.
You may be interested to read
This is a summary of: Naghdi S, and others. Clinical effectiveness of pharmacological interventions for managing chronic migraine in adults: a systematic review and network meta‑analysis. The Journal of Headache and Pain 2023; 24: 164.
Mistry H, and others. Competing interests for migraine: a headache for decision-makers. The Journal of Headache and Pain 2023; 24: 162.
Naghdi S, and others. Adverse and serious adverse events incidence of pharmacological interventions for managing chronic and episodic migraine in adults: a systematic review. BMJ Neurology Open 2024; 6: e000616.
Khanal S, and others. A systematic review of economic evaluations of pharmacological treatments for adults with chronic migraine. The Journal of Headache and Pain 2022; 23: 122
More information and regular events about migraine, including tips for how to manage symptoms, can be found on The Migraine Trust website.
The British National Formulary describes the drugs that might be used for migraine prevention.
Self-management tips can be found on the National Migraine Centre’s podcast, Heads Up.
Funding: This study was funded by the NIHR Health Technology Assessment programme.
Conflicts of Interest: One of the study authors has received funding from several pharmaceutical companies that produce drugs for migraine. See paper for full details.
Disclaimer: Summaries on NIHR Evidence are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that the views expressed are those of the author(s) and reviewer(s) at the time of publication. They do not necessarily reflect the views of the NHS, the NIHR or the Department of Health and Social Care.
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