BARCELONA — Physicians have a wide range of medications at their disposal for the treatment of acute migraine, including a host of older drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) and triptans, as well as newer ones, such as ditans and gepants.
Given all these choices, which medication should a physician prescribe to a patient with migraine? Specialists discussed the advantages and disadvantages of each in a debate session at the 17th European Headache Congress in Barcelona.
NSAIDs
Professor of Neurology Derya Uludüz of Istanbul University, Turkey, described the pros and cons of NSAIDs. Their analgesic effects come about by blocking the two isoforms of the enzyme cyclooxygenase (COX-1 and COX-2) to decrease the synthesis of prostaglandins, which are involved in migraine pathophysiology.
NSAIDs are most effective for treating migraines that have a slowly increasing intensity. Antiemetics can help enhance the absorption of NSAIDs like diclofenac, ibuprofen, naproxen, and indomethacin. Most NSAIDs have a favorable efficacy to side effect profile, do not influence blood pressure, and can also be used as acute detoxification therapy from migraine triggers.
The downside is that there is a risk for nephrotoxicity at higher doses, long duration of therapy, and in older people. NSAIDs should also be used with caution during the first and third trimester of pregnancy; acetaminophen and ibuprofen are safe to use during breastfeeding.
Triptans
Antoinette Maassen van den Brink, PhD, professor of pharmacology at Erasmus University in Rotterdam, the Netherlands, discussed triptans, a class of medications developed specifically for the treatment of acute migraine attacks. They act on vascular 5-hydroxytriptamine (5-HT) receptors to constrict the cranial arteries.
Triptans are generally effective and well tolerated. They are safe to use in clinical practice, despite their coronary vasoconstrictor properties. And although they are about as efficacious as NSAIDs when taken orally, "the subcutaneous formulation really has superior efficacy, so pharmacokinetics matter," said van den Brink.
Use of triptans is, however, associated with insufficient efficacy or tolerability, or both, in 30%-40% of people. Triptan nonresponders have significantly more severe migraines with higher frequency, intensity, and disability, so there is a large unmet need for effective treatment within this population.
Combination Therapy
Professor of Neurology Christian Lampl, Konventhospital der Barmherzigen Brüder Linz, Austria, and president of the European Headache Federation, discussed the benefits of combination therapy, noting that aspirin and paracetamol are among the most widely used drugs in the world and are often given together in combination with caffeine, as the APC formulation.
Meta-analyses show that this formulation is more effective than triptans are in treating acute migraine. When the primary outcome measure is pain relief 2 hours after dosing, it has an incidence of more than 54% compared with 34% for sumatriptan-naproxen.
"The nonprescription fixed triple combination is significantly more effective than other drugs in monotherapy or in combination, such as aspirin plus paracetamol," said Lampl. "It is effective, well tolerated, and is available nearly all over the world."
Lampl recommends a stepwise approach to provide patients with access to the right treatment. "The first thing to consider is the patient's preference," he told Medscape Medical News. "Then I would ask if they have any comorbidities, and what medication they have had before. If they are treatment naive, I'd start with 1 g of aspirin, and see how that works."
Gepants
Professor Jan Versijpt of University Hospital in Brussels, Belgium, described the benefits of calcitonin gene-related peptide (CGRP) antagonists, or gepants. These are monoclonal antibodies that bind to CGRP or its receptor to prevent the molecules from interacting. Three gepants have been developed to date, two of which, atogepant and rimegepant, are available in Europe.
"Gepants are a safe and well tolerated class of drugs with very low numbers of side effects," said Versijpt. "And based on preclinical and clinical data, we are pretty confident that they do not lead to medication overuse headache, which is a major leap forward in the way we treat migraine."
A very recent randomized, double-blind, placebo-controlled crossover trial carried out in the United States showed that ubrogepant is effective for treating migraine when taken during the prodrome.
"Efficacy is definitely a pro, albeit maybe not more effective than triptans, and safety is another pro, but we have to be aware that this is a young treatment class," said Versijpt. "There is also some indirect evidence that giving gepants as an acute treatment might have a preventive effect, but this would be very difficult to answer through randomized, controlled trials."
Ergot Alkaloids and Ditans
Finally, Christina Deligianni of Athens Naval Hospital Department of Neurology, in Greece, discussed the use of ergot alkaloids and ditans. Ergot alkaloids such as ergotamine and dihydroergotamine target 5-HT1B receptors, alpha-adrenoceptors, and dopamine D2 receptors, resulting in the inhibition of presynaptic neuropeptide release, arterial vasoconstriction, and antinociceptive effects. These drugs have been used to treat migraine for more than 50 years, but in 2013, the European Medicines Agency recommended severely restricting their use due to safety issues.
Ditans exert similar effects by specifically targeting presynaptic 5-HT1F receptors. The newest of these is lasmiditan, which appears to be an effective acute treatment option for patients with migraine seeking a fast onset of action but is associated with mild to moderate neurologic effects such as dizziness, nausea, and fatigue.
"If we have to compare it to the other drugs, we can see that lasmiditan 200 mg has the same efficacy as sumatriptan, ibuprofen, and aspirin, and is superior to gepants," said Deligianni. "It has no vasoconstriction side effects, so it should be the first choice for people with cardiovascular risk factors."
Moheb Costandi is a freelance writer based in London.
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