IMPORTANCEIn 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 PARTICIPANTSThis 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 MEASURESIncidence of serotonin syndrome. RESULTSThe 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 RELEVANCEThe 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.

We examined trends in management of headache disorders in United States (US) emergency department (ED) visits. We conducted a cross-sectional study using 2007–2018 National Hospital Ambulatory Medical Care Survey data. We included adult patient visits (≥18 years) with a primary ED discharge diagnosis of headache. We classified headache medications by pharmacological group: opioids, butalbital, ergot alkaloids/triptans, acetaminophen/nonsteroidal anti-inflammatory drugs (NSAIDs), antiemetics, diphenhydramine, corticosteroids, and intravenous fluids. To obtain reliable estimates, we aggregated data into three time periods: 2007–2010, 2011–2014, and 2015–2018. Using multivariable logistic regression, we examined medication, neuroimaging, and outpatient referral trends, separately. Among headache-related ED visits, opioid use decreased from 54.1% in 2007–2010 to 28.3% in 2015–2018 (Ptrend < 0.001). There were statistically significant increasing trends in acetaminophen/NSAIDs, diphenhydramine, and corticosteroids use (all Ptrend < 0.001). Changes in butalbital (6.4%), ergot alkaloid/triptan (4.7%), antiemetic (59.2% in 2015–2018), and neuroimaging (37.3%) use over time were insignificant. Headache-related ED visits with outpatient referral for follow-up increased slightly from 73.3% in 2007–2010 to 79.7% in 2015–2018 (Ptrend = 0.02). Reflecting evidence-based guideline recommendations for headache management, opioid use substantially decreased from 2007 to 2018 among US headache-related ED visits. Future studies are warranted to identify strategies to promote evidence-based treatment for headaches (e.g., sumatriptan, dexamethasone) and appropriate outpatient referral and reduce unnecessary neuroimaging orders in EDs.

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