A Case Series on Serotonin Syndrome from Concomitant use of linezolid With Methadone, Buprenorphine, and/or Dextroamphetamine

Background and Objectives: The risk of serotonin syndrome (SS), especially when linezolid is used concomitantly with methadone, buprenorphine, and/or dextroamphetamine, remains widely unstudied and may limit the options for antimicrobial therapy in these patient populations. Methods: We reviewed all adult encounters on linezolid with concomitant methadone, buprenorphine, and/or dextroamphetamine from April 2016 to June 2022. The primary outcomes included characterizing prescribing preferences and prevalence of confirmed and possible serotonin syndrome using ICD-10 diagnosis codes, cyproheptadine administration, and electronic medical record chart review using the Hunter Serotonin Toxicity Criteria. Results: Overall, 194 encounters were evaluated. 16.5%, 17.8%, and 7.1% were on high dose methadone, buprenorphine, and dextroamphetamine, respectively. Mean duration of overlap with linezolid was 4.6, 3.3, and 7 days respectively. One confirmed and two possible cases of serotonin syndrome were identified. Conclusion: Linezolid may be considered in patients who are concomitantly on methadone, buprenorphine, and/or dextroamphetamine. In our analysis of 194 encounters, one definitive case and two possible cases of SS were identified. Additional real-world studies are necessary to identify if exposure and/or duration may be correlated with an increased risk of serotonin syndrome.