What is the risk of serotonin syndrome when taking sumatriptan (Imitrex) and Ubrelvy (Ubrogepant)?

From the Guidelines

Combining sumatriptan and ubrelvy (ubrogepant) should be avoided due to the risk of serotonin syndrome. These medications work through different mechanisms but both affect serotonin pathways - sumatriptan is a serotonin receptor agonist while ubrelvy is a CGRP receptor antagonist with some serotonergic effects. When taken together, they can potentially cause excessive serotonin activity leading to serotonin syndrome, a potentially life-threatening condition characterized by agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and hyperthermia. According to the most recent guideline from 2024 1, there is insufficient evidence to recommend for or against any specific medication over another for the short-term treatment of migraine, but it emphasizes the importance of considering the risk of serotonin syndrome when combining medications that affect serotonin pathways. If you need migraine treatment, use only one of these medications at a time and maintain at least 24 hours between doses of different migraine medications. For example, if you've taken sumatriptan, wait at least 24 hours before taking ubrelvy, and vice versa. Always inform your healthcare provider about all medications you're taking, including over-the-counter drugs and supplements, as other serotonergic medications can further increase this risk. If you experience symptoms like confusion, agitation, fever, sweating, tremors, or muscle stiffness after taking these medications, seek immediate medical attention as these could indicate serotonin syndrome.

Some key points to consider:

• The risk of serotonin syndrome is low when combining triptans and SSRIs or SNRIs, but it is still a concern 1
• Ubrelvy (ubrogepant) is a CGRP receptor antagonist with some serotonergic effects, which can increase the risk of serotonin syndrome when combined with other serotonergic medications
• The 2024 guideline recommends considering the risk of serotonin syndrome when combining medications that affect serotonin pathways 1
• It is essential to inform your healthcare provider about all medications you're taking to minimize the risk of serotonin syndrome.

In terms of treatment options, the 2024 guideline suggests considering triptans, aspirin-acetaminophen-caffeine, and newer CGRP inhibitors (gepants) as options for treatment of acute migraine 1. However, the most critical consideration is to avoid combining medications that can increase the risk of serotonin syndrome. If you are taking sumatriptan and need to switch to ubrelvy, it is recommended to wait at least 24 hours before taking the new medication to minimize the risk of serotonin syndrome. Always prioritize your safety and consult with your healthcare provider before making any changes to your medication regimen.

From the Research

Serotonin Syndrome on Sumatriptan and Ubrelvy

• There are no direct studies on the combination of sumatriptan and Ubrelvy, but we can look at the available evidence on sumatriptan and serotonin syndrome.
• Sumatriptan is a selective agonist at serotonin 5-HT1-like receptors, including 5-HT1B/1D subtypes, and is used to treat acute migraine attacks 2.
• Serotonin syndrome is a potentially life-threatening complication of psychopharmacological drug therapy, characterized by alterations in cognition, behavior, autonomic nervous system function, and neuromuscular activity 3, 4.
• The FDA has warned about the potential risk of serotonin syndrome when triptans, such as sumatriptan, are used in combination with selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs) 5.
• However, the available evidence is limited to Class IV level of evidence, and there is no conclusive data to determine the risk of serotonin syndrome with the addition of a triptan to SSRIs/SNRIs or with triptan monotherapy 5.
• Clinicians should be cautious and vigilant to serotonin toxicity symptoms and signs to ensure prompt treatment, and health care providers should report potential cases to MedWatch and consider submitting them for publication 5.

Key Findings

• Sumatriptan is effective in treating acute migraine attacks, but may have a risk of serotonin syndrome when combined with other serotonergic agents 6, 2.
• The risk of serotonin syndrome with sumatriptan monotherapy is unclear, and more research is needed to determine the safety of this treatment 5.
• Clinicians should be aware of the potential risk of serotonin syndrome and monitor patients closely for symptoms and signs of this condition 3, 4, 5.