Concomitant use of opioid medications with triptans or serotonergic antidepressants in US office-based physician visits

Background: Opioids are not recommended for routine treatment of migraine because their benefits are outweighed by risks of medication overuse headache and abuse/dependence. A March 2016 US Food and Drug Administration (FDA) safety communication warned of the risk of serotonin syndrome from using opioids concomitantly with 5-hydroxytryptamine receptor agonists (triptans) or serotonergic antidepressants: selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Epidemiological information about co-prescribing of these medications is limited. The objective of this study was to estimate the nationwide prevalence of co-prescribing of an opioid with a serotonergic antidepressant and/or triptan in US office-based physician visits made by 1) all patients and 2) patients diagnosed with migraine. Methods: National Ambulatory Medical Care Survey (NAMCS) data were obtained for 2013 and 2014. Physician office visits that included the new or continued prescribing of >= 1 opioid medication with a triptan or an SSRI/SNRI were identified. Co-prescribed opioids were stratified by agent to determine the proportion of co-prescriptions with opioids posing a higher risk of serotonergic agonism (meperidine, tapentadol, and tramadol). Results: Of an annualized mean 903.6 million office-based physician visits in 2013-2014, 17.7 million (2.0% of all US visits) resulted in the prescribing of >= 1 opioid medication with a triptan or an SSRI/SNRI. Opioid-SSRI/SNRI was co-prescribed in 16,044,721 visits, while opioid-triptan was co-prescribed in 1,622,827 visits. One-fifth of opioid co-prescribing was attributable to higher-risk opioids, predominantly tramadol (18.6% of opioid-SSRI/SNRI, 21.8% of opioid-triptan). Of 7,672,193 visits for patients diagnosed with migraine, 16.3% included opioid prescribing and 2.0% included co-prescribed opioid-triptan. Conclusion: During a period approximately 2 years prior to an FDA warning about the risk of serotonin syndrome from opioid-SSRI/SNRI or opioid-triptan co-prescribing, use of these combinations was common in the USA. Studies on prescribing patterns following the March 2016 warning, and on the risk of serotonin syndrome associated with these co-prescriptions, are needed.