Risk of Serotonin Syndrome Associated with Antidepressant Use While on Linezolid Treatment

Abstract

Background: There is a potential drug interaction between linezolid and antidepressants resulting in serotonin syndrome. Thus, clinicians often avoid this drug combination. However, little empirical data exists to support this avoidance. The objective of this study was to describe the risk of serotonin syndrome in patients receiving linezolid and how this risk changed with concomitant antidepressant use. Methods: A population based retrospective cohort study was conducted using the administrative databases at ICES. The patient population consisted of outpatients aged 66 years or older who were prescribed oral linezolid of any duration from 2014 to 2021 in Ontario, Canada. Patients who were also taking antidepressants during linezolid treatment were compared to patients not on antidepressants during linezolid treatment. The primary outcome was clinically significant serotonin syndrome requiring emergency room visit or hospitalization based on physician diagnosis, Sternbach criteria or Hunter criteria within 30 days of starting linezolid. Secondary outcomes included altered mental status, hospitalization and death due to any cause within 30 days. Results: Of 1,134 patients who were prescribed linezolid, 215 (19.0%) patients were also taking antidepressants. Less than 6 (<0.5%) patients had serotonin syndrome. The proportion of patients with serotonin syndrome was numerically lower in the antidepressant group. In a propensity score matched cohort, the adjusted risk difference for serotonin syndrome in the antidepressant group minus the no antidepressant group was -1.2% (95% CI -2.9% to 0.5%). The risk of altered mental status, hospitalization and death were similar between the two groups. Conclusions: The risk of serotonin syndrome was low in patients taking linezolid. Concurrent antidepressants did not significantly increase the risk of serotonin syndrome. These findings suggest that linezolid can be safely used in patients also on antidepressants when indicated.