Migraine: Atogepant lowers rebound headache occurrence by 50%

There were 755 participants in the trial, each of whom experienced chronic migraine. Each had at least 15 days of headaches per month, with at least eight qualifying as migraine.

Out of the total group, 66% were overusing pain medications, which often occurs with people attempting to get rid of their headaches.

They were resorting to simple analgesics — such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or acetaminophen — for at least 15 days each month. Some took triptans or ergot alkaloids for at least 10 days. Some took a combination of both for at least 10 days in a month.

The trial began with a 4-week screening/baseline period.

At the beginning of the trial, participants averaged 18 to 19 migraine days per month, and were taking medications for pain for 15 to 16 days.

Next, individuals were randomly assigned to take 30 milligrams (mg) of atogepant twice daily, 60 mg of atogepant once each day, or a placebo for 12 weeks. During this period, they were monitored for the frequency of their painkiller use.

Participants who took atogepant took painkillers on fewer days during the trial. Additionally, a higher proportion of participants taking atogepant had a 50% or greater reduction in rebound headaches per month.

In general, said Goadsby, “[m]igraine is an inherited brain disease whose attacks are triggered by changes in the brain and changes in the external environment.”

“We know the path of physiology, but we don’t know what causes a migraine because there’s different triggers for different people,” Clifford Segil, DO, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in the study, told Medical News Today.

“For example,” he said, “many people with red wines versus white wines get it. Many people with cheeses get it. Caffeine both triggers headaches and treats headaches. So we’re still not entirely sure what causes the headaches.”

Modern, pharmaceutical therapies for migraine attacks fall into two camps: preventive and rescue. Atogepant is strictly a preventive drug, though it is closely related to two other drugs — ubrogepant and rimegepant — that are rescue and combination preventive/rescue drugs, respectively.

“Atogepant is a migraine preventive,” said Goadsby. “By taking it every day, the patient has less migraine and a much reduced need for acute treatments such as painkillers. In effect, it stops the attack before it starts.”

The drug “relaxes the [involved] blood vessel, which makes it get narrower and not as wide, and when it’s not as wide, it feels better,” Segil explained.

Goadsby also explained rebound headaches and why they occur. He told us that:

“Rebound headache occurs when a medicine taken to relieve an attack wears off and the headache returns. Say you have a migraine that is going to last 2 days. If you take a medicine on day one that lasts for 24 hours, then the headache will return (rebound) the next day, and you need to take another treatment.”

“A big problem with migraines is that people take too much medication, so we can get what’s called a ‘medication overuse headache’ or a ‘rebound’ headache. The easiest example is when someone has some pain, and they take a Motrin, Advil, or Alleve [or some other] NSAID every day,” Segil explained.

Goadsby also cautioned that some pain medications, such as NSAIDs, taken too often, can result in stomach ulcers and other assaults on the digestive tract.

“Taking pain medicines can, paradoxically, increase the number of migraine days the patient has so-called medication overuse headache, so taking fewer pain meds stops that happening,” he said.

According to Segil, over-use of pain meds may never give a migraine attack a chance to go away.

A migraine is a severe headache that is classically characterized by throbbing pain, sometimes covering half the head.

It may be accompanied by an uncomfortable sensitivity to bright lights and loud noises — photophobia or phonophobia, respectively — with or without blurry vision or a visual aura, a difficult-to-describe symptom in which vision becomes prismatic.

“Generally speaking, when people get migraines, there is a blood vessel between the brain and the skull in your meninges, and when the blood vessel gets too big, it dilates. It tugs on the meninges [which is] the shock absorber of the brain. That usually causes the throbbing pain,” Segil explained.

“After that, there’s irritation of the cortex of the brain, and a wave of electricity called cortical spreading depression, and that’s usually the radiating pain,” he detailed.