Co-Prescription of Opioids and Antidepressants Prevalent in Migraine

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Researchers sought to assess the prevalence of concomitant prescribing of opioid analgesics with a triptan or a serotogeneric antidepressant in individuals with migraine.

A combination of opioids and selective serotonin reuptake inhibitor (SSRIs) or serotonin-norepinephrine reuptake inhibitor (SNRIs) antidepressants was found to be prescribed more frequently than co-prescriptions of opioids plus triptans in patients with a migraine diagnosis, according to a study in Drug, Healthcare and Patient Safety

The combination of opioids with serotonergic antidepressants and/or triptans occurred more frequently in community-based care in US physician offices prior to the US Food and Drug Administration (FDA) warning concerning the risk of serotonin syndrome associated with co-prescribing of these medications.

The cross-sectional National Ambulatory Medical Care Survey (NAMCS) was used to obtain data on patient care in physician office visits between 2013 and 2014. Investigators focused on visits that resulted in new or continued prescriptions of ≥1 opioid medication combined with an SSRI/SNRI or a triptan. Additionally, the investigators stratified co-prescribed opioid medications by agent type to determine the levels of risk of serotonergic agonism with opioid co-prescribing.

Approximately 2.0% (n=17,667,548) of all US office-based physician visits between 2013 and 2014 included the prescribing of ≥1 opioid medication in combination with an SSRI/SNRI or a triptan. The co-prescribing of opioid medications with SSRIs/SNRIs occurred in 16,044,721 visits. Comparatively, the co-prescribing of opioids with a triptan occurred in 1,622,827 visits. Tramadol represented the most frequently prescribed high-risk opioid medication in the opioid-SSRI/SNRI and opioid-triptan combination groups (18.6% vs 21.8%, respectively). Higher-risk opioids were prescribed in up to one-fifth of all opioid co-prescribing practices. In addition, approximately 16.3% of visits for migraine included opioid prescribing, whereas 2.0% of visits resulted in co-prescribing of an opioid with a triptan.

The study is limited by the lack of available data on medication quantity and strength, factors which may influence excess serotonin agonism.

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Despite the initial benefits associated with co-prescribed pharmacotherapy for chronic pain conditions, the investigators of this study suggest that “health care providers should consider the risks associated with opioid use, particularly when co-prescribed with other serotonergic medications.”


Molina KC, Fairman KA, Sclar DA. Concomitant use of opioid medications with triptans or serotonergic antidepressants in US office-based physician visits. Drug Healthc Patient Saf. 2018;10:37-43.