Title: Prescribing Trends and the Risk of Serotonin Syndrome in Patients Receiving Linezolid and Serotonergic Medications
Authors: Clara Bishay, PharmD, MSMEd; Eric Kowalek, PharmD, BCPS; Danielle Kuhn, PharmD, BCPS
Learning Objectives:Audience members will be able to:
- Identify the risk of serotonin syndrome (SS) based on the existing literature.
- Describe the prescribing trends of the most commonly reported serotonergic agents (SAs) administered with linezolid and the associated risk of serotonin syndrome.
- Outline key study limitations, clinical significance, and areas for future research.
Methods: This retrospective, descriptive cohort study utilized electronic health record data collected between January 1, 2021, and August 1, 2025. Adult patients admitted to inpatient services who received an order for linezolid within 16 days of serotonergic agent administration were included; pregnant patients were excluded. Serotonin syndrome was identified by documented ICD-10 diagnosis and/or cyproheptadine administration. Data was analyzed using descriptive statistics, including measures of central tendency, dispersion, and percentages.
Results: Primary outcomes showed 69% of linezolid–serotonergic agent (SA) co-administrations had no provider or pharmacist interventions. Providers most often held/switched/dose-reduced SAs (49%), followed by holding/switching linezolid (31%) or no change (20%). Pharmacists recommended SA modifications in 78% of cases, no change with documented low serotonin syndrome (SS) risk in 17%, and linezolid changes in 5%. Patients were on 1–5 SAs; most interventions occurred with 1 (61%) or 2 (31%) SAs. Apart from one case, pharmacist interventions increased with SA count. No SS cases or cyproheptadine use were observed.
Conclusions: Pharmacists and providers often held or modified SAs despite the low incidence of serotonin syndrome (SS) reported in the literature. Avoiding SS through prescribing changes may lead to unintended consequences, including suboptimal infection management, withdrawal or worsening of comorbid conditions, and prolonged interruption of SAs. These findings support considering continuation of linezolid with SAs. No patients in this cohort experienced SS, consistent with published evidence.
Self-assessment Question: True or False: Linezolid should be avoided at all costs in patients taking SAs due to a high risk of SS.
