acute migraine

People who experience acute migraine may soon find relief in a new treatment. The results of a clinical trial of a novel drug revealed that it can eliminate head pain and reduce other symptoms of migraine.

Many people with acute migraine rely on triptans, a class of drugs that have been in use since the 1990s. However, triptans do not help everyone, and some people cannot take them because of their adverse side effects.

Triptans work by activating serotonin receptors, an effect that lowers inflammation and tightens blood vessels. As they constrict blood vessels, triptans are not suitable for people with or at risk of cardiovascular conditions.

The drug in the study, rimegepant, belongs to a new generation called gepants, which work in a different way than triptans.

Large-scale trial of novel migraine drug

People with migraine experience recurring attacks of head pain. Other symptoms, such as nausea and sensitivity to noise and light, can also occur. Once it develops, the condition often lasts for life.

Based on the results of a 2018 study, researchers estimated that more than 1 billion people, or 12–14% of the world’s population, experienced a migraine headache in 2016.

Although they are not as common as tension-type headaches, migraine headaches are responsible for the loss of more years to disability because of their more severe nature

Of the people that it affects, migraine will strike 75% at least once per month and severely impair 50% for the duration of the attack, which can last 4–72 hours.

The phase III trial tested the safety and efficacy of rimegepant in adults with acute migraine.

At 49 trial centers across the United States, investigators randomly assigned more than 1,000 women and men with migraine to receive either rimegepant tablets or placebo tablets that looked the same. The trial was a double-blind one, meaning that neither the participants nor the administrators who gave them the drugs knew who took the placebo and who took rimegepant.

The investigators instructed the participants to take a tablet when they experienced a migraine attack, and the pain had become moderate or severe.

Symptom relief with minimal side effects

The results showed that 19.6% of those who took rimegepant tablets had no pain after 2 hours compared with only 12.0% of those who took placebo tablets.

The investigators note that this difference is statistically significant, meaning that it was highly unlikely to be due to chance.

In addition, 37.6% of the participants in the rimegepant group experienced relief from their “most bothersome symptom” 2 hours after taking their tablet compared with 25.2% of those in the placebo group.

The most common side effects were nausea and urinary tract infection. The investigators observed no adverse cardiovascular effects.

A new era for migraine treatment

Migraine is a common medical condition, affecting as many as 37 million people in the US. It is considered a systemic illness, not just a headache. Recent research has demonstrated that changes may begin to occur in the brain as long as 24 hours before migraine symptoms begin. Many patients have a severe throbbing headache, often on only one side of the head. Some people are nauseated with vomiting. Many are light sensitive (photophobic) and sound sensitive (phonophobic), and these symptoms can persist after the pain goes away.

There are a variety of migraine subtypes with symptoms that include weakness, numbness, visual changes or loss, vertigo, and difficulty speaking (some patients may appear as if they are having a stroke). The disability resulting from this chronic condition is tremendous, causing missed days of work and loss of ability to join family activities.

It is sometimes possible for people to use an “abortive” medication, which, when taken early, can arrest the migraine process. For many patients, a preventive medication can decrease both the frequency and the severity of the migraines. But to date, many of the medications available for migraines have been developed primarily for other causes: seizures, depression, high blood pressure, and muscle spasms, for example. Researchers have been working for decades to develop a “targeted” preventive therapy specifically for migraine, and now we are finally close to having an exciting new treatment.

What does “targeted” therapy mean?

Calcitonin gene-related peptide (CGRP) is a molecule that is synthesized in neurons (nerve cells in the brain and spinal cord). It has been implicated in different pain processes, including migraine, and functions as a vasodilator — that is, it relaxes blood vessels. Once scientists identified this target molecule, they began trying to develop ways to stop it from being activated at the start of migraines, as a kind of abortive treatment. An agonist makes a molecule work more efficiently, and an antagonist blocks or reduces the molecule’s effect. The CGRP antagonist did work to decrease migraine pain based on certain measures, but there were some serious side effects including liver toxicity.

Monoclonal antibodies: Cutting-edge translational science

You have likely seen ads for monoclonal antibody (mAb) cancer and autoimmune therapies. There are lots of different types of mAbs, and while some harness a person’s own immune system to block replication of cancer cells, others stop a reaction in the body by binding to a target molecule or receptor and inhibiting it, thus preventing the reaction from continuing. The CGRP mAbs have this effect, and because they have a long duration of action (called a half-life), they can be administered much less frequently than typical migraine medications that are taken daily (with the exception of botulinum toxin, which is injected every 90 days). These new migraine medications are injected under the skin monthly, and have thus far demonstrated a statistically significant decrease in days of migraine. Four different drug companies are developing these new molecules, with two versions already sent to the FDA for approval.

What’s next?

If you think you may be a candidate for this new type of migraine medication, talk with your doctor, and perhaps ask for a consult with a neurologist or headache specialist who can help you understand more about the medication. Monoclonal antibody therapy is expensive, and there will likely be regulations about for whom s the treatments are appropriate. Much more research needs to be done about who is the best candidate for this therapy. But for many migraine patients who have not responded to the standard treatments, or who have had intolerable side effects such as cognitive dysfunction, low blood pressure, weight loss or gain, or other issues, CGRP monoclonal antibodies are safe and well tolerated, and are an exciting new development for migraine therapies.

Although migraine can’t be cured, there are treatments available which can help diminish the severity and frequency of the attacks, and to relieve symptoms during the acute headache.

Some patients with mild migraine can find relief with nonsteroidal anti-inflammatory drugs, or NSAIDs, such as ibuprofen or aspirin. However, there are other two types of drugs which are mainly used to treat acute attacks of migraine.

The two kinds of drugs used in the acute treatment of migraine are triptans (sumatriptan, almotriptan, rizatriptan, zolmitriptan, among others) and ergot derivatives (dihydoergotamine and ergotamine tartrate). They work by interfering with 5-HT receptors in the nervous system.

These drugs usually work best when they are taken as soon as the migraine begins, which is the reason why many people always carry their migraine medication with them. It is important to note that not every patient responds to each drug in the same way; this is why it’s so important to work together with your doctor to find a treatment that works for you.

Other medications work by preventing attacks, helping diminish their intensity or frequency. Most of these drugs were developed to treat other conditions; such as antidepressants, beta-blockers, and anticonvulsants. In some cases, when migraine is related to hormonal changes (such as a woman’s menstrual cycle), hormone therapy is used as preventive treatment.

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