OBJECTIVE: To discern the prevalence of concomitant use of a triptan and a selective serotonin reuptake inhibitor (SSRI) or a selective serotonin/norepinephrine reuptake inhibitor (SNRI) in the USA. BACKGROUND: In July, 2006, the US Food and Drug Administration warned patients and health-care professionals to be aware that use of a triptan in combination with an SSRI or an SNRI may result in a potentially life-threatening problem known as serotonin syndrome. METHODS: We used weighted data from the US National Ambulatory Medical Care Survey for years 2003 and 2004 to derive national estimates of the number of office-based visits documenting concomitant use of a triptan and an SSRI or an SNRI. RESULTS: During the time frame 2003-04, an annualized mean of 3,874,367 patients were prescribed a triptan, and 50,402,149 patients were prescribed an SSRI or an SNRI. An annualized mean of 694,276 patients were simultaneously prescribed or continued use of a triptan along with an SSRI or SNRI. CONCLUSION: Our study documents that 1.3% of patients prescribed a triptan or an SSRI or an SNRI were prescribed the potentially fatal combination. While this is a small fraction overall, the actual number of patients on a nationwide basis is significant (n=694,276).