What is the interaction between sertraline (Selective Serotonin Reuptake Inhibitor - SSRI) and sumatriptan (Imitrex, 5-Hydroxytryptamine Receptor Agonist)?

From the Guidelines

Taking sertraline and sumatriptan together requires careful medical supervision due to the potential risk of serotonin syndrome, a serious drug interaction that can cause symptoms ranging from mild to severe. When considering the interaction between sertraline and sumatriptan, it's essential to prioritize the risk of serotonin syndrome, which can occur when there's excessive serotonin in the body. According to the most recent evidence 1, the risk of serotonin syndrome with combining triptans and SSRIs or SNRIs is low, but still requires caution.

Key Considerations:

• Sertraline is an SSRI that increases serotonin levels throughout the body, while sumatriptan activates serotonin receptors specifically in blood vessels, which can create dangerous serotonin excess in the brain and nervous system.
• The risk of serotonin syndrome increases with higher doses of either medication, and symptoms can range from mild (agitation, tremor, diarrhea) to severe (high fever, seizures, muscle rigidity).
• If prescribed both medications, it's recommended to take sumatriptan only as needed for migraines, not regularly, and at the lowest effective dose.
• Monitoring for early warning signs of serotonin syndrome, including confusion, rapid heart rate, dilated pupils, muscle twitching, or excessive sweating, is crucial, and patients should contact their doctor immediately if these symptoms develop. As noted in the guideline evidence 1, caution entails starting the second non-MAOI serotonergic drug at a low dose, increasing the dose slowly, and monitoring for symptoms, especially in the first 24 to 48 hours after dosage changes.

Recommendations:

• Use the lowest effective dose of sumatriptan when taking sertraline.
• Monitor for symptoms of serotonin syndrome, and seek medical attention immediately if they occur.
• Consider alternative treatments for acute headache if possible, especially in situations where the risk of serotonin syndrome may be higher, such as in perioperative settings 1.

From the FDA Drug Label

There have been rare post marketing reports of serotonin syndrome with use of an SNRI or an SSRI and a triptan If concomitant treatment of SNRIs and SSRIs, including sertraline, with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases Sumatriptan There have been rare postmarketing reports describing patients with weakness, hyperreflexia, and incoordination following the use of a selective serotonin reuptake inhibitor (SSRI) and sumatriptan. If concomitant treatment with sumatriptan and an SSRI (e.g., citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) is clinically warranted, appropriate observation of the patient is advised. Serotonin syndrome may occur with sumatriptan tablets, particularly during co-­administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions (7.4)].

The interaction between sertraline and sumatriptan may increase the risk of serotonin syndrome, which can be life-threatening.

• Careful observation of the patient is advised when using these medications together, particularly during treatment initiation and dose increases.
• Monitoring for symptoms of serotonin syndrome, such as mental status changes, autonomic instability, neuromuscular aberrations, and gastrointestinal symptoms, is necessary.
• The use of sumatriptan and sertraline together should be approached with caution due to the potential risk of serotonin syndrome 2 3.

From the Research

Interaction between Sertraline and Sumatriptan

• The concomitant use of sumatriptan and selective serotonin reuptake inhibitors (SSRIs) like sertraline is currently contraindicated due to the risk of serotonin syndrome 4, 5.
• However, a study published in 1995 found that 14 patients receiving fluoxetine, fluvoxamine, sertraline, or other antidepressant treatments did not experience significant side effects when taking oral sumatriptan for migraine relief 4.
• Another study in 1998 reported that the concurrent use of sumatriptan with an SSRI or lithium has been associated with symptoms suggestive of serotonin syndrome in some cases, but the majority of patients tolerated the combination without incident 5.
• A case report in 1996 described six patients with migraine who developed symptoms suggestive of serotonin syndrome after taking sumatriptan or dihydroergotamine while on serotomimetic agents, including sertraline 6.
• The safety and efficacy of sertraline in treating mood and anxiety disorders have been well established, but its interaction with sumatriptan requires careful consideration 7.
• Current treatment guidelines for acute migraine attacks recommend triptans, including sumatriptan, as first-line medications, but caution against their use in patients taking SSRIs or other serotonergic agents due to the risk of serotonin syndrome 8.