Most effective migraine drugs revealed by review of trial data

An underused category of drug appears more effective for managing migraine-related symptoms than newer, costlier medications, according to a sweeping review of clinical trials.

Despite being designed specifically to treat migraine episodes, triptan drugs are used in less than 22 per cent of migraine cases. Providing that patients have no medical conditions that preclude their use, such as cardiovascular disease, the results suggest people should consider low-cost triptans as a first-line treatment for migraine relief, says Andrea Cipriani at the University of Oxford.

“It’s not a bad idea to pull all the data together and re-emphasise – particularly to primary care physicians – that if someone comes in with migraine and they’ve got no contraindication, and they’ve tried [non-steroidal anti-inflammatory drugs], the evidence base for using the triptans is really quite good,” says Peter Goadsby at King’s College London, who wasn’t involved in the review.

Triptans, such as sumatriptan and eletriptan, have been progressively authorised globally since 1991 and are now available as off-brand or generic tablets. However, case reports have suggested that the drugs may trigger heart attacks or strokes – especially in people with pre-existing cardiovascular issues.

To offer alternative treatments, pharmaceutical companies developed newer drugs called ditans and gepants – which have a similar mechanism of action to triptans but avoid the cardiovascular risks. Licensed only in the past few years, these drugs – lasmiditan, rimegepant and ubrogepant – come at a high cost. For example, Eli Lilly’s trademarked formulation of lasmitidan, Reyvow, retails for $92.50 per 24-hour tablet, compared with about $17 for generic eletriptan.

People also have the option of taking non-steroidal anti-inflammatories (NSAIDs), such as ibuprofen, and analgesics, such as paracetamol, to control their migraine symptoms.

While researchers have carried out hundreds of studies investigating the efficacy, safety and side effects of each of the many drugs and drug classes used to treat migraines, there had been a lack of work comparing them with each other, says Cipriani. To take advantage of the vast amount of existing knowledge, he and his colleagues analysed 137 double-blind, randomised controlled trials carried out worldwide since 1991.

With a total of 89,445 adult participants, the trials assessed the efficacy of 17 oral medications in comparison with either a placebo or one of the other drugs. The team judged the drugs’ performance using recommended criteria from the International Headache Society, including how well the medications managed pain over a 2-hour period or throughout 24 hours following regular dosing.

Their results revealed that the most effective drug for pain relief at the two-hour mark was the triptan eletriptan, followed by three other triptans: rizatriptan, sumatriptan, and zolmitriptan.

Eletriptan and ibuprofen were the most effective drugs for sustained pain relief up to 24 hours.

Lasmiditan, rimegepant and ubrogepant, however, were no more effective in relieving the clinical signs of migraine than paracetamol and most of the NSAIDs – and they carried a higher risk of side effects, such as nausea. As such, these drugs should be considered “third-line options”, says Cipriani.

The findings suggest that some people would benefit from treating their migraines with certain triptans. But that doesn’t mean they are the right solution for everyone, adds co-author Elena Ruiz de la Torre at the European Migraine and Headache Alliance, in Brussels. “Migraine is a very personal disease,” she says.

“You really have to do the best thing for the person sitting in front of you,” says Goadsby. Meta-analyses like this one can’t offer much insight at a personal level, he says. “They tell you about a population, but they’re very blunt instruments for trying to understand what’s going on at an individual level.”

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