Serotonin syndrome is a serious drug reaction that can lead to agitation, high blood pressure, seizures, and death when left untreated. After several reports of serotonin syndrome by patients taking the antibiotic linezolid (a reversible monoamine oxidase inhibitor) and antidepressants, the Food and Drug Administration in 2011 warned against linezolid therapy for patients taking serotonergic psychiatric medications. A study published yesterday in JAMA Network Open now suggests that patients taking linezolid and antidepressants are not at a significantly increased risk of serotonin syndrome.
Despite being “ideal as first-line or step-down oral antibiotic therapy for bacteremia and pneumonia as well as skin and soft tissue infections,” linezolid use “has been limited because of concerns of drug interactions,” wrote Anthony D. Bai, M.D., of Queen’s University in Ontario, Canada, and colleagues. “However, data on the risk of serotonin syndrome associated with linezolid are scarce,” they added.
To assess the incidence of serotonin syndrome in patients receiving oral linezolid and antidepressants, Bai and colleagues analyzed data collected by ICES—an independent, nonprofit research institute funded by the Ontario Ministry of Health. The researchers focused on 1,134 patients aged 66 years and older in Ontario, who were prescribed oral linezolid for any duration from October 1, 2014, to January 1, 2021. Of these patients, 215 (19%) were taking antidepressants (103 patients were taking a selective serotonin reuptake inhibitor, 36 were taking a serotonin-norepinephrine reuptake inhibitor, 15 were taking a tricyclic antidepressant, and 7 were taking a norepinephrine and dopamine reuptake inhibitor; none were taking a monoamine oxidase inhibitor). The researchers specifically focused on clinically significant serotonin syndrome within 30 days of starting linezolid treatment that required an ambulatory care visit, emergency department visit, or hospitalization.
According to the analysis, serotonin syndrome occurred in fewer than 6 patients (<0.5%) in total.
Bai and colleagues matched 166 patients who were taking antidepressants with 166 patients who were not. “In this propensity score–matched cohort, the risk of serotonin syndrome was lower in the antidepressant group, with an adjusted risk difference of −1.2% (95% CI, −2.9% to 0.5%; P = .50),” the authors wrote. “Within this 95% CI, the worst-case scenario would be a 0.5% increase in the risk of serotonin syndrome due to antidepressants, which is equivalent to a number needed to harm of 200,” they wrote.
Bai and colleagues concluded, “These findings suggested that linezolid is likely safe for patients receiving antidepressants. Nevertheless, prescribers should remain vigilant for this potential drug interaction.”
(Image: iStock/Hiraman)
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