Patients Taking SSRI/SNRIs, Triptans Rarely Experience Serotonin Syndrome

In 2006, the Food and Drug Administration (FDA) issued a health advisory warning that patients who take selective serotonin reuptake inhibitors or selective norepinephrine reuptake inhibitors (SSRIs/SNRIs) together with triptan antimigraine drugs may be at a heightened risk of serotonin syndrome—a potentially fatal condition believed to arise from elevated serotonin levels. This advisory was based on 27 case reports of suspected serotonin syndrome in people who had been treated with triptans and SSRIs/SNRIs.

A population-based study published on February 26 in JAMA Neurology found serotonin syndrome was rare in patients who were co-prescribed triptans and SSRI/SNRI antidepressants.

“Our results cast doubt on the validity of the FDA advisory and suggest that it should be reconsidered,” Yulia Orlova, M.D., Ph.D., a professor of neurology at the University of Florida College of Medicine, and colleagues wrote.

Orlova and colleagues analyzed data from the Partners Research Patient Data Registry to identify over 19,000 patients who had received a prescription for both triptans and SSRI/SNRIs at some point between January 1, 2001, and December 31, 2014. The Partners registry contains health record information for more than 6 million members of the Partners HealthCare Network in the greater Boston area.

Of these 19,000 patients, 229 received a diagnosis of an extrapyramidal disease—the broad category of drug-induced disorders that serotonin syndrome falls under in the International Classification of Diseases—during the study period. Orlova and her colleagues took a closer look at these medical records and identified 17 of these cases in which the clinician had suspected serotonin syndrome. Seven of the 17 cases occurred during a year in which the patient had a documented prescription of both triptans and SSRI/SNRIs; however, only two of these seven cases could be classified as definite serotonin syndrome based on the symptoms meeting the requirements of one of the two primary measures used to diagnose serotonin toxicity: the Hunter criteria or the Steinbach criteria.

In total, these two cases resulted in an incidence rate of serotonin syndrome of 0.6 cases per 10,000 person-years of medication exposure—a rate lower than the estimated prevalence of serotonin syndrome among people who only take SSRIs. Even if it was assumed that serotonin syndrome occurred in all patients in whom it was clinically suspected and with documented co-prescription, the resulting incidence rate would still be only 2.3 cases per 10,000 person-years of medication exposure. “Overall, our results are reassuring and suggest that patients with coexisting affective disorders and migraine need not forgo management of one condition to treat the other,” Orlova and colleagues wrote.

As a complementary analysis, the authors also explored the trends of triptan-SSRI/SNRI co-prescribing practices between 2001 and 2014, a period that spans when the FDA health advisory was released. The number of patients receiving a triptan prescription rose steadily during this period, from 1,444 in 2001 to 17,353 in 2014. During this same time, the percentage of patients co-prescribed an SSRI or SNRI antidepressant remained stable.

“The steady co-prescription rate suggests that the medical community, based on their experience, had already accepted the potential risk to achieve the benefits of treating these two very commonly co-existing disorders,” Orlova told Psychiatric News.

Despite some limitations of the trial—clinicians may have not recognized or properly coded incidents of serotonin syndrome and the authors could not know the precise length of time meds were used—Orlova said the estimates will better prepare patients and physicians to discuss the risks and benefits of these medications. Given the potential severity of serotonin syndrome, Orlova said she thinks it would be valuable to give serotonin syndrome its own diagnostic code to better identify and track suspected cases.

This study was supported by the Harvard Catalyst. ■