Triptans (like Imitrex) mix well with antidepressants

September 1, 2017

Sumatriptan (Imitrex), rizatriptan (Maxalt) and the other 5 triptans work on serotonin receptors to stop a migraine attack. Many antidepressants, such as fluoxetine (Prozac), escitalopram (Lexapro), that belong to the SSRI family and venlafaxine (Effexor) and duloxetine (Cymbalta), that belong to the SNRI family of drugs also affect serotonin or its receptors. Because both triptans and antidepressants affect serotonin, it is understandable that there has been concern about the potential for serotonin-related side effects when these drugs are used together.

In 2006 the FDA released a warning, “Potentially Life-Threatening Serotonin Syndrome With Combined Use of SSRIs or SNRIs and Triptan Medications.” Fortunately, this is the case of “fake news”. My colleague in Houston, Dr. Randy Evans under the Freedom of Information Act, requested all the data that the FDA used to issue this warning. He published an article on his findings and concluded that “The data do not support prohibiting the use of triptans with SSRIs or SNRIs.”

A new study presented at the 59th Annual Scientific Meeting of the American Headache Society confirmed Dr. Evans’ conclusion. Dr. Yulia Orlova and her colleagues at the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston conducted a population-based study using information on more than 6.5 million patients. Over a 14-year period, about 19,000 were prescribed both triptans and SSRI or SNRI antidepressants. Between 4 and 7 patients (0.02% to 0.04%) developed serotonin syndrome.

In most cases serotonin syndrome is mild and consists of shivering, sweating, and diarrhea. Only very rarely it can be life-threatening with high body temperature, agitation, and seizures.

This is an important issue because migraine is 2-3 times more common in those suffering from depression and anxiety, while depression and anxiety are 2-3 times more common in people with migraines. This means that millions of people suffer from both conditions. Most experts agree that combining SSRIs and SNRIs with triptans is very safe.

A similar issue is the prohibition on mixing different triptans within 24 hours. There is not a slightest shred of clinical or scientific evidence for this contraindication. Nevertheless, the FDA-approved label has this warning for every triptan.

Written by
Alexander Mauskop, MD
Continue reading
November 15, 2025
Cluster headaches
Cluster headaches and solar activity
It was an unusual week at the New York Headache Center. After months of relative calm, my schedule suddenly filled with cluster headache patients—one even consulting me virtually from Saudi Arabia. The influx came right after a G5-level geomagnetic storm, one of the strongest solar events in recent memory.
Read article
November 10, 2025
Alternative Therapies
A Week of Meditation Changes Brains and Bodies
A week-long meditation retreat produces dramatic changes in brain and metabolic functions
Read article
October 21, 2025
Alternative Therapies
Meditation is better than slow breathing exercise in reducing pain
A new study published in the journal PAIN by Dr. A. Amorim and her colleagues at the University of California San Diego examined how mindfulness meditation reduces pain. The findings help clarify whether mindfulness meditation is more effective than simple slow breathing for pain relief.
Read article