Researchers still are trying to unravel the mystery of the intense form of head pain known as migraine. If you suffer from this debilitating neurological condition, relief is never as simple as taking aspirin, NSAIDs or other painkillers. Migraine is a highly individualized disorder that needs a personalized medication regimen…and even that may not work all the time. But there is hope—new classes of drugs are emerging along with new ways of using existing medications. Bottom Line Personal spoke with migraine specialist Brian M. Grosberg, MD, to learn more about the new treatments and what is coming in the future.

Two Ways to Treat

There are two prongs to migraine treatment—medications that work to reduce frequency…and acute medications to relieve attacks once they occur.

A migraine-prevention regimen is appropriate if…

You have frequent or long-lasting migraines. Frequent means having headaches more than four days per month. Long-lasting means not getting consistent benefit (90% to 100% relief) within two hours of migraine onset and complete functionality following treatment.

Your migraine causes significant disability or loss of quality of life.

You don’t get relief from acute migraine medicine…the medicine causes unbearable side effects…or you can’t take NSAIDs because of gastrointestinal ulcers or triptans because of heart disease. (A triptan may narrow coronary blood vessels.)

You’re at risk for medication-overuse headaches—when you take acute medications more than two days a week over an extended period. Medications that may result in this risk are opiates and barbiturate-containing combination analgesics, such as Fioricet and Fiorinal.

You have menstrual migraines, which can be very severe, longer lasting and less responsive to acute treatment.

You have depression and anxiety, ­obesity, other pain disorders or allodynia, sensitivity to things that aren’t normally uncomfortable such as brushing your hair or wearing glasses. With any of these conditions, you are at higher risk for increased migraine frequency.

Preventive medications typically are aimed at people with episodic and chronic migraine, and they can help prevent episodic migraine from becoming chronic. Nearly 40% of people with migraine could benefit from preventive therapy, but only about 10% have tried it.

Game changer: CGRP antagonists are drugs that block calcitonin gene-related peptide (CGRP), a protein that causes blood vessels in the nervous system to dilate, triggering pain. They have been proven effective for chronic and episodic migraine prevention.

The four large-molecule CGRP antagonists—called monoclonal antibodies—are erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality) and eptinezumab (Vyepti). Aimovig, Ajovy and Emgality are self-administered injections. Vyepti is given intravenously in a hospital or outpatient infusion center every three months.

Small-molecule CGRP antagonists, known as gepants and available in pill form, were first used for treatment of acute migraine. Atogepant (Qulipta) was the first gepant developed exclusively as a preventive treatment for episodic migraine. In three- and 12-month studies on episodic migraine, it was shown to be safe and effective, reducing monthly migraine days by more than four days. Also, participants needed less medication to stop an attack and were able to cut monthly sick days by half or more. Another gepant, rimegepant (Nurtec), is approved to prevent episodic migraine and can be taken every other day.

What’s new in preventive treatment: In April 2023, atogepant (Qulipta) was approved for prevention of chronic migraine. It reduced monthly migraine days by an average of seven when participants took 60 mg daily. Separate research found that Qulipta is a viable treatment for people who weren’t helped by other classes of preventive medications.

In the pipeline: Ongoing research includes the first head-to-head comparison of a small-­molecule CGRP drug versus a large-molecule one. In contrast to large-molecule CGRP antagonists, which have a half-life (the time it takes for the drug’s active substance in your body to reduce by half) lasting about a month, small-molecule CGRP antagonists are oral medications with shorter half-lives that leave the body more rapidly, so you need less medication.

When You have a migraine

Preventive medications don’t work for everyone or don’t work all the time, so sufferers need to have migraine-relief medications in their arsenals. These drugs can take one to two hours to work, so they should be taken at the first sign of a migraine and in the exact dose prescribed. Gepants have replaced triptans for many sufferers, especially those with heart disease who can’t take triptans because of potential effects on blood vessels.

What’s new in acute treatment: Ubrogepant (Ubrelvy) received FDA approval for treatment of acute migraine in adults in December 2019. Approved in March 2023, zavegepant (Zavzpret) became the latest gepant and first fast-acting nasal spray. It comes premeasured to deliver 10 mg into one nostril and can be used once a day. Studies have found that zavegepant can start to ease pain in 15 minutes, allow people to function normally in 30 minutes and feel pain-free in two hours—an effect that lasted 48 hours.

Nasal sprays are good for people who don’t respond to oral drugs. Within the last few years, nasal sprays have become a more popular delivery method for older migraine medications as well, including sumatriptan (Tosymra) and dihydroergotamine mesylate (Trudhesa).

Nondrug Treatment

Give yourself the best possible chance of relief by making lifestyle changes that will have the greatest impact…

Keep a comprehensive journal of your migraines, medications, etc. Include a food diary—many foods have been linked to migraine, but they differ from person to person—and a record of your activities, including not only work absenteeism but also presentism, when you’re where you’re supposed to be but not functioning at your normal capacity.

Stick to a schedule. Lifestyle factors that impact migraine are exercise or lack of it, missed sleep and sleep disturbances, and stress. Beware of the letdown phenomenon—the level of endorphins, released when you are under stress, is high during the week but come Friday, those endorphins drop, you stay out late, your sleep schedule is off…and you get a migraine.

Consider losing weight. Weight loss from bariatric surgery has been linked to less frequent migraines. Research is underway to study whether medical weight loss, achieved with a drug such as Ozempic, has the same effect.

Try mind-body practices. Cognitive behavioral therapy (CBT) teaches you to change thought patterns and behaviors. Biofeedback, relaxation therapies like deep breathing and mindfulness mediation, and yoga also are helpful.

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