How Gepants and Ditans Complement Existing Therapies

Dr. Jessica Ailani explains how new therapies differ from migraine treatments on the market

Ditans and gepants are new migraine treatments that differ slightly from existing therapies. These new medications provide additional options for people with migraine for whom other medications may put at risk of side effects. AMF spoke with Dr. Jessica Ailani, director of the MedStar Georgetown Headache Center in Washington, D.C., about what makes gepants and ditans different from existing migraine treatments and how these new options will help patients find relief from their migraine symptoms.

Ditans and gepants are both medicines that can be taken as needed and swallowed in pill form or as a dissolvable tablet at the onset of an attack to treat symptoms like headache pain, light/sound sensitivity, nausea and vomiting. “They target very specific [receptors on sensory nerves] that can lead to resolution of migraine symptoms,” says Dr. Ailani.

How gepants differ from monoclonal CGRP antibodies (anti-CGRPs)

Calcitonin gene-related peptide (CGRP) is a protein that carries pain signals along nerves that are involved in generating the headache pain associated with migraine. Gepants work to block CGRP from attaching to its receptor and initiating those pain signals.

Gepants are different from the 3 injectable CGRP monoclonal antibodies in a few ways. Gepants are oral pills or dissolvable tablets versus an injectable. “Gepants, at least at this time, are approved to take on an as needed basis versus an injection or infusion which are given to prevent attacks of migraine and are delivered under the skin once monthly or every three months, depending on the particular antibody. says Dr. Ailani.

Additionally, it takes a few months for the CGRP monoclonal antibodies to be eliminated, whereas gepants will be completely eliminated over the course of a few days.

How ditans differ from triptans

Dr. Ailani still considers triptans a “gold standard medication” for acute treatment of migraine, which she would give to patients of the appropriate age who don’t have vascular conditions like uncontrolled blood pressure or a prior stroke or heart attack.

“I think of ditans as a relative of the triptans, like a younger sister, younger brother,” Dr. Ailani says. Triptans act on two specific receptors that are found on sensory nerves, but one of the receptors is also on blood vessels, she says, and “can sometimes come with constriction of blood vessels which if diseased or prone to spasm, could lead to complications

Ditans are more specific and don’t affect blood vessels. “The receptor that they’re working on is not located in a blood vessel, so it doesn’t cause that vessel to get smaller and restrict blood flow. So to me, that’s like the next generation.”

Dr. Ailani would continue to use triptans as a first-line but would consider ditans for older patients with a history of heart disease or stroke or who have other medical conditions that increase their risk for heart attacks or stroke. Ditans could also be useful for patients who do not respond to triptans or have side effects from triptans.

“The limitation of a ditan is that they are potentially sedating, have an 8-hour driving restriction and are a controlled substance,” Dr. Ailani says, “So this might limit the patient population that I would put on that product.” However, they may be useful for patients whose attacks usually occur at night or awaken patients from sleep, where patients will either be going to bed or back to sleep.

How both medications are changing the game for patients

When a patient is dissatisfied with their migraine treatment, ditans and gepants can make a big difference. More acute treatments like these, for instance, can reduce the need for patients to travel for clinical care. Gepants, in particular, have no known risk of medication overuse headache. “It not only didn’t seem that the frequency of headache becomes greater over the course of the clinical trials, but two recent trials have shown that using them daily actually reduces headache frequency.  There is a very good chance that they’re not going to cause medication overuse headache,” says Dr. Ailani.

These treatments can be a huge relief to patients, especially those with frequent attacks, says Dr. Ailani. “We always limit treatment, so sometimes a person comes in to see us and they’re having 10 to 12 attacks a month and it’s difficult for the patient to hear you might not be able to treat every attack.”

“To be able to instruct a patient that the minute they feel symptoms of a migraine to take their medicine and not be concerned about medication overuse headache is revolutionary and could potentially change the disease course itself,” she says.

The American Migraine Foundation recommends patients speak to their doctors about these medications to learn more about their treatment options.

This article discusses gepants and ditans, two new classes of migraine treatments. For more specific information about each of the three FDA-approved treatments, lasmiditan, ubrogepant and rimegepant, please refer the American Headache Society website.