Review of: Orlova Y, JAMA Neurology 2018;E1–E7

In 2006, the FDA issued a warning that patients using either selective serotonin reuptake inhibitors or selective norepinephrine reuptake inhibitors (SSRIs or SNRIs) together with triptan antimigraine drugs might be at a heightened risk for serotonin syndrome. Their advisory was based on 27 case reports of suspected serotonin syndrome in people who were prescribed a triptan along with one of these serotonergic antidepressants.

Because migraines are a common comorbidity in depressive and anxiety disorders, many of our patients are co-prescribed these medications. But what is the true risk for serotonin syndrome for these patients?

Yulia Orlova at the University of Florida and colleagues from Boston’s Brigham and Women’s Hospital completed a population-based study to evaluate this risk. They used electronic health records from over 6 million members in the Partners Research Data Registry to identify a cohort of 19,017 patients, who were prescribed both triptans and an SSRI or SNRI between 2001 and 2017, a total of 30,928 person-years of exposure.

Serotonin syndrome was suspected in 17 patients, and concurrent use of triptans and SSRI/SNRI was confirmed in 7 of these. Serotonin syndrome was considered definite in 2 of those cases and possible in the other 5, yielding an incidence rate of 0.6–2.3 cases per 10,000 person-years of exposure.

The rate of co-prescription did not change after the 2006 FDA warning. Between 2001 and 2014, 21%–29% of triptan users were also prescribed an SSRI or SNRI.

TCPR’s Take
Serotonin syndrome is hypothesized to involve activation of only serotonin 2A and 1A receptors. Triptans are primarily agonists for serotonin 1B and 1D receptors and do not activate serotonin 2A or 1A receptors. Thus, we doubt that triptans would increase the risk of serotonin syndrome.

This study supports that conclusion. The risk of serotonin syndrome with concomitant use of triptans and SSRIs or SNRIs appears to be very low. These results cast serious doubt on the validity of the 2006 FDA advisory and suggest that it should be reconsidered.