Tryptophan as a Modulating Factor in the Antimigraine Efficacy of Triptans

Migraine is a leading cause of disability worldwide. Triptans are medications used to treat migraine attacks. They work mainly in two ways: by narrowing the blood vessels in the brain and by stopping the release of substances that cause pain and inflammation. Triptans help relieve migraine pain and other symptoms, like digestive problems, light sensitivity, and disability during an attack. However, more than 20% of patients do not respond well to these medications, and the reasons for this are not well understood.

Tryptophan is an essential amino acid, which means it must come from food because the body cannot produce it. Tryptophan plays an important role in migraines, especially through its by-products, such as serotonin and kynurenine. Research has shown that problems with tryptophan metabolism can make migraines worse, along with other sensory symptoms.

Although no study has directly linked tryptophan to the effectiveness of triptans, the investigators found in a preclinical study that a low-tryptophan diet could reduce the effectiveness of sumatriptan, one of the most commonly used triptans. A deficiency in tryptophan can occur when the body has trouble absorbing it from the intestines. Conditions like inflammatory bowel diseases (such as irritable bowel syndrome or Crohn's disease) or diabetes can affect this absorption, which might reduce the body's ability to process tryptophan.

This study aims to better understand how tryptophan might affect resistance to triptans in migraine patients. The investigators will compare blood levels of tryptophan and its by-products in patients who respond well to triptans versus those who do not. If participants are having a lumbar puncture as part of their regular check-up, the investigators will also examine these substances in the cerebrospinal fluid. Additionally, the investigators will explore any connection between tryptophan metabolism and inflammatory bowel disease.

Inclusion criteria

• Cisgender women, premenopausal, aged 18 to 50 years.
• Cisgender men, aged 18 to 50 years.
• Diagnosed with migraine (according to ICHD-3 criteria).
• Diagnosed as responders or non-responders to triptans (according to the criteria of Sacco et al., 2022).
• Permitted comparison groups include: triptans used alone or in combination with other migraine treatments (e.g., NSAIDs, acetaminophen, ergotamine, opioids, antiemetics).
• All routes of administration and all dosages.
• Affiliation with a social security system.

Exclusion criteria

• Patients under guardianship, curatorship, deprivation of liberty, or legal protection
• Pregnant and breastfeeding women