Triptans with SSRIs or SNRIs: 14 years of records found two definite cases of serotonin syndrome in 30,928 person-years
19,017 patients were co-prescribed a triptan and an SSRI or SNRI in Boston over 14 years. Two had definite serotonin syndrome, 0.6 per 10,000 person-years; five more were possible. The authors say the FDA advisory "should be reconsidered."
Well-supported by good-quality research. how we score evidence
Caveat on this rating: One health system, retrospective, and dependent on a serotonin syndrome diagnosis having been recorded; mild cases managed without a diagnosis code would be missed, which would push the true rate up. The study argues against the advisory; the FDA has not, to our knowledge, withdrawn it, and the labels still list triptans.
The labels list triptans among the drugs that raise serotonin syndrome risk with antidepressants. This is the study that measured the combination and found the risk close to zero.
Significant findings
Orlova, Rizzoli and Loder (JAMA Neurology, 2018) searched electronic health records of the Partners system in greater Boston for patients diagnosed with anything compatible with serotonin syndrome who had also been co-prescribed a triptan and an SSRI or SNRI, from January 2001 to December 2014. "A total of 19 017 (±3) patients were coprescribed triptans and antidepressants during the study, with a total of 30 928 person-years of exposure."
"Serotonin syndrome was suspected in 17 patients. Only 2 patients were classified as having definite serotonin syndrome (incidence rate, 0.6 cases per 10 000 person-years of exposure; 95% CI, 0.0-1.5). Five patients were classified as having possible serotonin syndrome (incidence rate with these 5 cases added to the 2 definite cases, 2.3 cases per 10 000 person-years of exposure; 95% CI, 0.6-3.9)."
The advisory did not change practice: "The proportion of patients with triptan prescriptions who were coprescribed an SSRI or SNRI antidepressant was relatively stable during the study, ranging from 21% to 29%." The conclusion, verbatim: "The risk of serotonin syndrome associated with concomitant use of triptans and SSRIs or SNRIs was low. Coprescription of these drugs is common and did not decrease after the 2006 FDA advisory. Our results cast doubt on the validity of the FDA advisory and suggest that it should be reconsidered."
Worth asking
This is the row that keeps the rest of the wave honest. A listed interaction is a warning that a mechanism exists, not a measurement of how often it hurts anyone; here, when someone measured, the answer was about one definite case per 15,000 years of combined use. If you have migraines and depression, the combination is common, and the question for the prescriber is what symptoms would prompt a call, not whether the two can be prescribed together at all.
Source
Association of Coprescription of Triptan Antimigraine Drugs and Selective Serotonin Reuptake Inhibitor or Selective Norepinephrine Reuptake Inhibitor Antidepressants With Serotonin Syndrome — Orlova Y, Rizzoli P, Loder E (2018)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1001/jamaneurol.2017.5144
DOI: 10.1001/jamaneurol.2017.5144
How this was scored
- Study design
- Cohort study
- Funding
- Independently funded
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 19,017
- Preregistered
- not recorded
- Conflicts disclosed
- Yes
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "strong evidence". Well-supported by good-quality research. It scores 74 out of 100 on our published rubric. One caveat travels with that badge: One health system, retrospective, and dependent on a serotonin syndrome diagnosis having been recorded; mild cases managed without a diagnosis code would be missed, which would push the true rate up. The study argues against the advisory; the FDA has not, to our knowledge, withdrawn it, and the labels still list triptans. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Association of Coprescription of Triptan Antimigraine Drugs and Selective Serotonin Reuptake Inhibitor or Selective Norepinephrine Reuptake Inhibitor Antidepressants With Serotonin Syndrome — Orlova Y, Rizzoli P, Loder E (2018). Published in: Top-tier peer-reviewed journal. DOI: 10.1001/jamaneurol.2017.5144. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Cohort study. Funding: Independently funded. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.