Association of Coprescription of Triptan Antimigraine Drugs and Selective Serotonin Reuptake Inhibitor or Selective Norepinephrine Reuptake Inhibitor Antidepressants With Serotonin Syndrome

JAMA Neurol. 2018 May 1;75(5):566-572. doi: 10.1001/jamaneurol.2017.5144.


Importance: In 2006, the US Food and Drug Administration (FDA) issued an advisory warning on the risk of serotonin syndrome with concomitant use of triptans and selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) antidepressants, but the true risk of serotonin syndrome in these patients remains unknown.

Objective: To assess the risk of serotonin syndrome with concomitant use of triptans and SSRI or SNRI antidepressants.

Design, setting, and participants: This study used electronic health record data from the Partners Research Data Registry (RPDR) to identify patients who had received an International Classification of Diseases, Ninth Revision diagnosis compatible with serotonin syndrome who had been coprescribed triptans and SSRI or SNRI antidepressants in the Greater Boston, Massachusetts, area from January 1, 2001, through December 31, 2014 (14 years). Clinical information was extracted to determine whether the case met formal diagnostic criteria and had coprescription within a calendar year. Both conservative and broad case definitions were used to better characterize the spectrum of risk. Data analysis was performed from November 23, 2016, to July 15, 2017.

Main outcomes and measures: Incidence of serotonin syndrome.

Results: The RPDR search revealed 47 968 (±3) unique patients who were prescribed triptans during the 14-year period of the study. 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 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%.

Conclusions and relevance: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / adverse effects*
  • Electronic Health Records
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Migraine Disorders / drug therapy
  • Prescriptions / statistics & numerical data
  • Retrospective Studies
  • Serotonin Syndrome / chemically induced*
  • Serotonin Syndrome / epidemiology*
  • Serotonin Uptake Inhibitors / adverse effects*
  • Tryptamines / adverse effects*


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Tryptamines