Migraines: effective molecules to relieve pain

Forget paracetamol. Faced with migraine, a tablet of Doliprane or Dafalgan is almost always useless. To relieve the pain, the patient must resort to a non-steroidal anti-inflammatory drug (NSAID), useful for combating the painful inflammation of the arteries supplying the meninges and the brain.

But also, and above all, to drugs called triptans, which were invented for migraine sufferers. They work by attacking the dilation of blood vessels while mimicking the effect of serotonin, a chemical messenger in the brain.

About 30 years ago, these triptans were a major breakthrough in patient care. "For one in three patients, two hours after treatment, the pain has completely disappeared," says Jérôme Mawet, neurologist at the Lariboisière-Fernand-Widal University Hospital (Paris). And for many others, it goes from an unimaginable intensity to a bearable level.

These differences in effectiveness, explains Anne Ducros, from the Montpellier University Hospital, are partly due to taking too late: “Whether with a triptan or an NSAID, the drug must be administered within one hour of the onset of the crisis.

Another imperative pointed out by the neurologist: “Above all, do not start with paracetamol and then switch to a triptan or an NSAID if the crisis does not pass.” This is indeed a major cause of non-response to treatment. However, this is extremely rare.

"To be considered non-responsive to triptans, you must be in failure with at least two of them, and to be qualified as refractory, at least three, including the one dispensed with an auto-injector pen", specifies Professor Ducros . The injection may indeed be necessary in the event of nausea or vomiting, situations for which there are also NSAIDs and antinauseants in suppositories, or triptans in nasal spray.

So can all migraine attacks be relieved? Unfortunately no. Because triptans face a limit: they are contraindicated in case of uncontrolled high blood pressure or cardiovascular history (stroke, heart attack, etc.). To circumvent the problem, other drugs targeting serotonin levels have been developed: ditans, recently available in the United States, but not yet in France.

"Research also focused on molecules targeting the receptor for a pain mediator called CGRP," says Dr. Mawet. Called gepans, they turn out to be a little less effective than triptans as crisis treatments, but have the advantage of a possible preventive effect. The only downside, according to Professor Ducros, "a possible rebound effect highlighted in some studies".

These drugs are nonetheless eagerly awaited, one of them having just obtained marketing authorization (AMM) at European level. But hopes rest above all on other molecules: so-called monoclonal antibodies that neutralize CGRP. For Benoît, who tested them, it was a “rebirth”: from 15 to 20 attacks per month, with unbearable pain, i.e. 9 out of 10 on the intensity scale, he went to 3 or 4 monthly attacks without more impact than a mild headache.

"Anti-CGRPs halve seizures, and can even make them disappear, while being extremely well tolerated," comments Dr. Mawet. Two of them, to be injected under the skin, have recently been sold in pharmacies. And a third could soon be dispensed once a quarter at the hospital, intravenously.

At least, in theory… Because the Transparency Commission, responsible for evaluating the usefulness of drugs, considers that they do not provide greater benefit than other preventive treatments, and has therefore aligned their reimbursement with the price of the latter - a few euros, when their selling price in France varies between 250 and 300 euros. A prohibitive cost!

And a decision contested both by patients and by neurologists specializing in migraine, who do not fail to draw a parallel with triptans or botulinum toxin, sometimes used against migraine: it took years to get their refund. “We must not make patients lose all hope, nuances Dr. Mawet. For some, conventional preventative treatments work.”

What are these molecules? These are drugs initially intended to treat hypertension, epilepsy, or depression, but administered in often lower doses. Their weak point? Significant side effects - sedation, weight gain, etc. - which lead a majority of migraine sufferers to discontinue treatment.

Antidepressants can, however, be useful and even indispensable, administered in therapeutic doses. Because as pointed out by Christian Lucas, neurologist at the Lille University Hospital and President of the French Society for the Study of Migraines and Headaches, "migraine is the only neurological disease where, intrinsically and genetically, there is a anxiety-depressive comorbidity”.

Taking these anxious or depressive traits into account is all the more crucial when the migraine is severe. And in addition to appropriate medication, it requires care by a health professional who can, among other things, rely on behavioral and cognitive therapies. While waiting for other advances which can, we hope, provide even better relief from this chronic pathology. Patients are waiting for them: “The journey of a migraine sufferer is punctuated by drug trials,” notes Joana.

It was women who first noticed it: if injections of Botox, or botulinum toxin, erased their wrinkles, they are also beneficial for their migraine. A dozen years ago, American studies proved the effectiveness of this toxin on chronic migraine - a form of the disease where there are more days with headache than without. It has received the approval of the French health authorities for this indication in 2021. Between 31 and 39 injection points must be performed in the hospital, in the neck and around the eyes, every three months. Result: crises attenuated sometimes from the first session, even after two or three.