Serotonin Syndrome; what is it?

I frequently get asked about serotonin syndrome from my patients and their primary care providers. Serotonin is a natural chemical messenger in the brain that helps regulate mood, sleep, and pain perception; all important factors in migraine. However, when too much serotonin builds up in the body, it can cause a potentially dangerous reaction called serotonin syndrome. This condition occurs when serotonin levels rise excessively, usually due to certain medications that increase serotonin activity. Symptoms can range from mild (tremor, sweating, agitation) to severe (fever, muscle rigidity, confusion, and in rare cases, life-threatening complications).

For those with migraine, serotonin syndrome may be something to be aware of. Many commonly used migraine medications, particularly triptans (such as sumatriptan, rizatriptan, or eletriptan), work by stimulating specific serotonin receptors to help relieve migraine pain. On their own, triptans rarely cause serotonin syndrome. However, the risk can increase when they are taken together with other medications that also affect serotonin levels, such as SNRIs (serotonin-norepinephrine reuptake inhibitors like venlafaxine or duloxetine) or SSRIs (selective serotonin reuptake inhibitors such as sertraline or escitalopram), which are sometimes prescribed for depression, anxiety, or chronic pain prevention.

However, evidence suggests if you are taking one SNRI/SSRI while on a triptan, you are not at an increased risk of serotonin syndrome. This risk does amplify if you are on a multitude of serotoninergic treatments.  I always educate my patients about the early signs of serotonin syndrome, including restlessness, rapid heartbeat, fever and chills, dilated pupils, diarrhea, or feeling unusually “amped up.” These symptoms can appear within hours of taking interacting medications. Fortunately, serious cases are rare, especially in the setting of proper patient education.

References:

Evans RW, Tepper SJ, Shapiro RE, Sun-Edelstein C, Tietjen GE. The FDA alert on serotonin syndrome with use of triptans combined with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors: American Headache Society position paper. Headache. 2010 Jun