The Paralyzed Stomach During Migraine Attacks: How to Treat Migraine with Gastroparesis

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Scott Szymanski, VP of Sales and Marketing at Tonix Pharmaceuticals, was attending a meeting when one line caught his attention—something about how clinicians who treat migraines should be aware that GLP-1 slows stomach emptying, causing gastroparesis.

“The light bulb went off that we have a huge need in the migraine market to explain the benefits of non-oral medications—that you can actually bypass the gut, get the medication the bloodstream a lot quicker—and that inspired me,” Szymanski told HCPLive.

Following this realization, Tonix Pharmaceuticals launched a national awareness campaign, “Does Your Migraine Pill Work Every Time?”, to highlight the impact of gastroparesis on the absorption of oral migraine medications.¹ The campaign debuted at PAINWeek in Las Vegas and aimed to educate both patients and healthcare providers about the benefits of non-oral treatments, such as nasal and injectable options.

The campaign’s impact did not stop there. In October 2024, Tonix expanded the initiative by launching an educational website.² The site serves as a resource for clinicians to educate patients on the connection between gastroparesis and migraine. Additionally, Tonix partnered with a brand to launch a prescription request system and telemedicine platform, streamlining access to migraine specialists and reducing barriers.

More than 37 million people in the United States experience migraine attacks, according to the American Migraine Foundation.³ On top of that, The World Health Organization recognizes migraine as one of the top 10 most disabling medical illnesses. Despite the high prevalence and debilitating nature of migraines, only about 564 headache specialists were certified by the United Council of Neurologic Subspecialties (UCNS) in headache medicine as of 2020. Moreover, < 5% of patients with migraine have been seen by a healthcare provider or received an accurate diagnosis.^4,3

As for gastroparesis, approximately 25 out of every 100,000 people are diagnosed, though many more cases likely go underdiagnosed.⁵ The connection between migraine and gastroparesis often goes unnoticed.

At the annual North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) meeting, Christian Sadaka, MD, from the Children’s Hospital of Philadelphia (CHOP) told HCPLive that migraine was a frequent comorbid condition of gastroparesis, but he did not think the two were correlated.

“We see it frequently in gastroparesis patients, but I don't see a direct link between the two,” Sadaka said.

Link or no link, evidence suggests that gastroparesis can occur during, before, or between migraine attacks. Gastroparesis during a migraine attack is caused by a complex interplay between the central nervous system and the autonomic nervous system—a blood migraine connection.

“What's been known for a long time is that attacks of migraine cause gastroparesis, meaning during a migraine attack, your stomach stops functioning normally,” Christopher H. Gottschalk, MD FAHS, professor of clinical neurology at Yale School of Medicine, told HCPLive. “What's become clear over time is that it's also true that people who have migraine are much more likely to have gastroparesis in between attacks, so when patients end up getting referred to a GI doctor for problems with absorption, problems with abdominal pain and bloating, etc., [they] ultimately are found to have gastroparesis unless they have some other illness.”

Gastrointestinal (GI) specialists recognize that in the absence of other conditions, such as diabetes or chemotherapy, migraines are likely the cause of gastroparesis.

In some cases, gastroparesis symptoms may overshadow migraines. Gottschalk provided an example of an 8-year-old who complains of a stomachache and a headache—an undiagnosed migraine. Still, migraine symptoms often dominate over GI symptoms.

Gastroparesis impacts the effectiveness of migraine treatments. A 2013 paper reported that oral triptans are not the optimal therapy for patients who have migraine-associated gastroparesis because these medications rely on gastric motility and gastrointestinal absorption, which are impaired in the presence of gastroparesis.⁶

“If there's gastroparesis, it means the stomach is just sitting there quiet and doesn't do anything,” Gottschalk explained. “So that combination of inactivity and lack of moving things through means, even if a pill goes in the stomach and gets dissolved by acids, it doesn't get absorbed because the stomach doesn't absorb anything.”

Oral tablets may be convenient and often preferred, but alternative treatment options exist. Injectable treatments bypass gastric stasis and deliver medication directly into the bloodstream, but they can be uncomfortable and may increase adverse events or exacerbate nausea and vomiting.

Nasal sprays are another option, which are rapid but only partially bypasses gastric statis problems. They can have drawbacks, such as an unpleasant taste that worsens nausea, potential nasal irritation, and the administration is indiscreet.

The efficacy of nasal sprays varies. The generic form of sumatriptan nasal spray drizzles the medicine into the nose, which drips down the throat and gets absorbed into the stomach. Gottschalk said studies have shown that this type of nasal spray delivers less medicine to the patient than taking a pill. Zolmitriptan works slightly better, but as Gottschalk pointed out, it is a matter of timing.

A newer formulation, Tosymra, combines sumatriptan with sugar molecules, enabling faster and more efficient absorption through the nasal mucosa compared with oral tablets.

Orally disintegrating tablets provide convenience without needing water, though their taste can exacerbate nausea, and their effectiveness depends on gastrointestinal absorption.

Research has shown that certain medications, such as aspirin, can help correct gastroparesis during a migraine attack. Studies have demonstrated that if aspirin is taken during a migraine attack, the absorption of aspirin is cut down by more than half. If someone takes an aspirin when they do not have a migraine, they have normal absorption. Taking medication during an attack can help restore normal absorption and function of the stomach.

Zeil Rosenberg, MD, MPH, executive vice president of Tonix Pharmaceuticals, shared with HCPLive that 80 to 100% of patients with migraine experience gastroparesis, and the slowing of the stomach during a migraine attack is a universal experience.

“Delayed emptying is not only almost universal, but it also contributes to a lot of other problems you see with migraine, such as nausea and vomiting abdominal pain with the others of bloating,” Rosenberg said.

Gottschalk emphasized the need for new research on the connection between gastroparesis and migraine, particularly regarding the timing and extent of reduced drug absorption during a migraine. Research has yet to pinpoint whether the reduced triptan absorption begins at the start of the attack, at the start of pain, or 30 minutes to an hour into the attack. Regardless, Gottschalk said patients should take a migraine medicine as early as possible.

“Once people understand that their stomach isn't really functioning during an attack—and that's why their treatments don't work reliably, or they take too long or just seem to be failing—the light goes on about what's actually happening in their bodies,” Gottschalk said. “It makes a huge difference in terms of how they think about treatment, why early treatment is important, why it's worth moving to a spray or an injection because at least you're getting the medicine that you think you're getting.”

References

1. ^{Tonix Pharmaceuticals Launches National Awareness Campaign on the Impact of Gastroparesis or Stomach Paralysis on the Absorption of Oral Migraine Medications at PAINWeek. Tonix Pharmaceuticals. September 6, 2024. https://ir.tonixpharma.com/news-events/press-releases/detail/1514/tonix-pharmaceuticals-launches-national-awareness-campaign. Accessed January 28, 2025.}
2. ^{What’s the Connection Between Gastroparesis (GP) and Migraine? https://gpmigraine.com/. Accessed January 28, 2025.}
3. ^{American Migraine Foundation. https://americanmigrainefoundation.org/resource-library/migraine-facts/. Accessed January 28, 2025.}
4. ^{Minen MT, Wells RE, Gautreaux JR, Szperka CL, Rayhill M, Orlova Y, Metzler A, Halpern A, Monteith T. Responding to the Needs of Early Career Physicians and Fellows in Headache Medicine: Career Planning, Getting Involved, and Considerations in Building a Headache Center. Headache. 2020 Jul;60(7):1453-1462. doi: 10.1111/head.13833. Epub 2020 Jun 1. PMID: 32476142; PMCID: PMC7768978.}
5. ^{Wills E, Thompson JO, Koller FL. Top 10 Facts You Need to Know about Gastroparesis. JMSMA. 2022;63(9).}
6. ^{Newman LC. Why triptan treatment can fail: focus on gastrointestinal manifestations of migraine. Headache. 2013 Jun;53 Suppl 1:11-6. doi: 10.1111/head.12111. PMID: 23721285.}