Linezolid and Serotonin Syndrome

Linezolid and Serotonin Syndrome


  • Manufacturer labeling warns against concomitant use of multiple serotonergic agents due to an increased risk of serotonin syndrome (SS)
  • These combinations are listed as “contraindicated” in the Micromedex® drug-interaction database
  • Co-administration of linezolid and serotonergic agents was not associated with SS in pre-marketing clinical trials
  • However, in post-marketing surveillance (1997-2003), 29 cases of linezolid-associated serotonin toxicity have been reported
  • Published reports show a low incidence of SS with concomitant use of linezolid and serotonergic agents (0.24-4%)
  • Linezolid-associated SS does not appear to have high mortality, with most cases resolving upon removal of causative agents and supportive care

Clinical Considerations

  • SS typically presents with the initial symptoms of agitation and tremor, and may progress to more severe symptoms
  • SS can occur 30 minutes to 21 days from time of co-administration
    • May occur later in older patients as compared to younger patients
    • The majority of cases occur within 6-24 hours after co-administration


  • The incidence of SS with concomitant use of serotonergic agents and linezolid is low
  • The manufacturer labeling warns against concomitant use but post marketing literature suggests this is not a contraindication
  • Close patient monitoring and provider awareness are essential, and discontinuation of inciting agent(s) is necessary with advent of SS symptoms

Scripps Recommendations

E.g. selective serotonin reuptake inhibitor (SSRI) or serotonin-norephinephrine reuptake inhibitor (SNRI)

Educate all healthcare providers and patients on signs and symptoms of SS

Monitor patients on multiple serotonergic agents during hospital stay

Discontinue serotonergic agents if SS is suspected

More Information

  1. Lawrence KR, Adra M, Gillman PK. Serotonin Toxicity Associated with the Use of Linezolid: A Review of Postmarking Data. Clin Infect Dis 2006;42:1578-1583.
  2. Morales-Molina J. Linezolid-associated serotonin syndrome: what we can learn from cases reported so far. J Antimicrob Chemother. 2005;56(6):1176-1178.
  3. Ramsey T, et al. Serotonergic and Adrenergic Drug Interactions Associated with Linezolid. Ann Pharmacother. 2013;47(4):543-560.
  4. Taylor JJ, Wilson JW, Estes LL. Linezolid and Serotonergic Drug Interactions: A Retrospective Survey. Clin Infect Dis. 2006;43:180-7.
  5. Woytowish MR, Maynor LM. Clinical Relevance of Linezolid-Associated Serotonin Toxicity. Annals of Pharmacotherapy. 2013;37:388-397.