Observed incidence of linezolid-associated serotonin syndrome during concomitant serotonergic therapy

Purpose: While confirmed cases of serotonin syndrome have been documented with linezolid, the incidence in patients receiving linezolid in combination with other serotonergic medications is unknown. A retrospective study and a survey estimate the incidence to be somewhere between 3 and 25%. This prospective observational study was conducted to investigate the incidence of serotonin syndrome in hospitalized patients initiated on linezolid.

Methods: A CPOE-based report of active linezolid orders was generated daily from March 1, 2012 to June 15, 2012. All adult patients receiving linezolid were included. Patients receiving concomitant medications with serotonergic activity were monitored daily for signs and symptoms of serotonin syndrome. The primary outcome, development of serotonin syndrome, was diagnosed either by the patient care team as definitive or through satisfying the Hunter Serotonin Toxicity Criteria (HSTC). Descriptive statics were utilized to describe data.

Results: Of the 130 unique courses of linezolid included in the study, 37 (28.5%) received concomitant therapy with at least one serotonergic agent. Seventy-five percent of the 37 were on a single concomitant serotonergic agent (8.3% on 2, 16.7% on 3). Median duration of linezolid therapy was 78 hours (range 12-444 hours). While serotonin syndrome was mentioned on the differential diagnosis for one patient, no patients met the HSTC. No cases of serotonin syndrome were observed in this patient population during hospitalization.

Conclusion: Linezolid-associated serotonin syndrome may be very rare in practice, despite use with multiple serotonergic agents. Further observation of the use of linezolid in patients receiving concomitant serotonergic agents is needed in order to describe the true incidence of this seemingly rare, potentially life-threatening reaction.