Aida Lopez had her first migraine attack as a teenager in the 1990s. By the time she was 23, she was experiencing debilitating pain, vomiting, and sensitivity to light two to three times a week. Some days she couldn't get out of bed. Eventually she went to a neurologist, who prescribed a triptan (a type of drug used to treat migraine). The medication helped initially, but the pain usually returned within hours. She later took a different triptan, then an opioid analgesic, and finally an antiseizure medication, none of which provided sufficient relief. Her neurologist diagnosed her with intractable migraine, meaning it was resistant to treatment.
In 2020, another neurologist prescribed ubrogepant (Ubrelvy), one of a newer class of migraine medications called gepants, to treat attacks. In January 2023, Lopez added a beta-blocker for migraine prevention. The combination has changed her life, says Lopez, now 45, a university instructor in Miami. “For 20 years I felt like I was almost dead. Now I feel and function so much better. Even when I do get migraine attacks, they're less frequent and milder, and after I take the ubrogepant, they go away.”
Gepants, like the one Lopez takes, are among the newest medications for migraine, along with another group of drugs called ditans, which include lasmiditan (Reyvow). They're providing relief for many people who didn't benefit from or couldn't take other medications. “The last five years have been an amazing time in the field of migraine,” says Jessica Ailani, MD, FAAN, director of the MedStar Georgetown Headache Center in Washington, D.C. “There are so many more treatment options, and they're better tolerated, so people stay on them longer.”
Thae gepant drugs prevent calcitonin generelated peptide (CGRP)—a protein that carries pain signals along nerves—from att aching to its receptor and initiating the pain associated with migraine. Unlike the injectable CGRP monoclonal antibodies used to prevent migraine, gepants can be taken orally and as needed to treat attacks. Starting in 2019, four gepants have been approved by the U.S. Food and Drug Administration: ubrogepant, rimegepant (Nurtec), atogepant (Qulipta), and zavegepant (Zavzpret). All are oral medications except Zavzpret, which is a nasal spray prescribed for acute migraine. (Rimegepant also can be used to prevent an attack.)
Ditan drugs, like the older triptans, target serotonin receptors but do not appear to narrow blood vessels as triptans do, so they can be used by people with cardiovascular disease, says Amaal Starling, MD, FAAN, a headache specialist at Mayo Clinic in Scottsdale, AZ. The oral drug lasmiditan is the first ditan approved for the treatment of acute migraine.
“Before these new medications, we relied on drugs that were approved for other conditions—such as propranolol for hypertension, topiramate for seizures, or amitriptyline to treat depression—and they became migraine drugs,” says Kathleen B. Digre, MD, FAAN, chief of the division of headache and neuro-ophthalmology at the University of Utah in Salt Lake City. “For acute migraine treatment, we had triptans and ergotamines, but they were difficult to use and had side effects, and some didn't work very well.”
Gepants can be used at the first signs of an attack—when unusual fatigue, dizziness, brain fog, or sensitivity to light occurs—before the pain kicks in, says Peter Goadsby, MD, PhD, professor of neurology at King's College London and professor emeritus at UCLA. “These herald the real possibility of eliminating pain in migraine.” While these new medications can relieve pain, studies suggest they won't eliminate migraine altogether.
Unlike triptans, gepants don't carry the risk of medication overuse headaches (also known as rebound headaches), which are triggered by excessive use of analgesics. “Gepants can reduce the frequency of migraine attacks if you take them every second day,” Dr. Goadsby says. Ditans can cause sedation, so there's an eight-hour driving restriction after taking them, Dr. Ailani says.
For people who respond only partially or not at all to other medications, a gepant or ditan is worth considering, says Teshamae Monteith, MD, FAAN, associate professor of neurology and chief of the headache division at the University of Miami Miller School of Medicine. “Not all people respond to these newer drugs, but among those who do, some feel they are lifesavers.”
A phase 3 double-blind trial published in the New England Journal of Medicine in 2021 found that when adults who had four to 14 migraine days per month took atogepant once a day for 12 weeks, they had on average four fewer headache days per month—a significant improvement.
More recently, a study in the March 2023 issue of Cephalalgia compared the safety and efficacy of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine and found they all had benefits and drawbacks. While 200 mg of lasmiditan provided the most relief from pain after two hours, it also caused more dizziness, nausea, and drowsiness. Rimegepant yielded slightly less pain relief than lasmiditan, and ubrogepant had the fewest side effects.
Unfortunately, these newer drugs aren't all covered by insurance as a first-line treatment. “Most insurance companies will want people to try several triptan medications and prove they were ineffective or poorly tolerated,” Dr. Starling says. If your physician documents that you have contraindications (such as severe vascular disease) for triptans, your insurance company is more likely to cover alternatives, she says.
For people not getting sufficient relief for their migraine attacks from current treatments, Dr. Starling urges them to talk to their doctors about these new options.
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