Clinical Relevance of Linezolid-Associated Serotonin Toxicity

Woytowish, Melanie; Maynor, Lena

doi:10.1345/aph.1r386

Cited by 50 publications

(43 citation statements)

References 34 publications

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“…In conducting a comprehensive medication list review, it is important to be cognizant of all potential sources for increased circulating serotonin: increased serotonin synthesis, augmented serotonin release, blockade of serotonin reuptake from the synapse, inhibition of serotonin metabolism, direct antagonism of serotonin receptors, and increased postsynaptic response to serotonin (Woytowish and Maynor 2013) (see Table 17.1). Medication sources include traditional antidepressant medications (selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs,) bupropion, mirtazepine, etc.…”

Section: Serotonin Syndromementioning

confidence: 99%

“…), herbal supplements (St. John's Wort, L-tryptophan), and opioid pain medications (methadone, fentanyl, codeine). Illicit drugs including Table 17.1 Serotonergic agents organized by mechanism of increasing serotonin concentration and drug class [Woytowish and Maynor (2013) Meperidine is frequently used to block chills associated with antifugal infusions cocaine, amphetamines, MDMA (3,4-methylenedioxymethamphetamine), and lysergic acid diethylamide (LSD) can influence circulating serotonin levels. There are other drugs with significantly different, nonpsychiatric active clinical purpose which are known to influence serotonin levels (linezolid, procarbazine, meperidine.)…”

Section: Serotonin Syndromementioning

confidence: 99%

“…There are other drugs with significantly different, nonpsychiatric active clinical purpose which are known to influence serotonin levels (linezolid, procarbazine, meperidine.) Additionally severe hepatic dysfunction will decrease CYP450 enzyme activity thereby increasing concentrations of SSRIs which are normally excreted/metabolized through this pathway (Woytowish and Maynor 2013). Serotonin toxicity is protean in its clinical presentation and nature.…”

Section: Serotonin Syndromementioning

confidence: 99%

“…They may appear slightly agitated, hypervigilant, or exhibit pressured speech (Quinn and Stern 2009). Overall, the presence of clonus is thought to be the most important clinical finding to support a diagnosis of serotonin toxicity (Woytowish and Maynor 2013;Quinn and Stern 2009).…”

Section: Serotonin Syndromementioning

confidence: 99%

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Psychiatric Emergencies

Lynn¹,

Valentine²

2014

Psychopharmacology in Oncology and Palliative Care

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The complexity of oncology and supportive care is such that psychotropic drugs are themselves potential causes of urgent or emergent clinical problems. Polypharmacy and medication interactions increase the risk of drug-related emergencies. Serotonin syndrome is characterized by mental status changes, autonomic hyperactivity, and neuromuscular abnormalities varying from mild to life-threatening. Use of standardized diagnostic criteria can be helpful. Neuroleptic malignant syndrome presents with muscle rigidity, mental status changes, autonomic instability, and hyperpyrexia. Treatment of both syndromes is focused on removal of the precipitating agents and supportive interventions. Psychotropic drugs that are well tolerated in healthy persons are potentially dangerous in high acuity and end stage disease settings. Overdose and intoxication with psychotropic drugs are usually accidental or idiosyncratic in oncology and supportive care though the medications might be used in suicide attempts. Benzodiazepine intoxication risks hypotension, decreased respiratory drive, and exacerbation of delirium. Antipsychotic drugs may cause or exacerbate anticholinergic delirium. Typical and second generation antipsychotics may cause or exacerbate dangerous cardiac conduction delays including torsades de pointes. Antidepressants, frequently involved in suicides, are variably toxic or lethal between classes. Tricyclic antidepressants and monoamine oxidase inhibitors are particularly dangerous. In all cases of psychotropic drug intoxication or overdose treatment involve withdrawal of offending agents and support of affected organ systems. Emergencies related to psychotropic drugs are

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Section: Serotonin Syndromementioning

confidence: 99%

Section: Serotonin Syndromementioning

confidence: 99%

Section: Serotonin Syndromementioning

confidence: 99%

Section: Serotonin Syndromementioning

confidence: 99%

See 2 more Smart Citations

Psychiatric Emergencies

Lynn¹,

Valentine²

2014

Psychopharmacology in Oncology and Palliative Care

View full text Add to dashboard Cite

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“…However, numerous more serious adverse effects were reported after commercial release, including thrombocytopenia, lactic acidosis, peripheral and optic neuropathy, and serotonin syndrome (Narita et al 2007 ;Jang et al 2009 ;Woytowish et al 2013). A general feature of the oxazolidinone class of antibiotics is the inhibition of mammalian mitochondrial protein synthesis effected by binding to mitochondrial ribosomes in all tissues (Barnhill et al 2012 ).…”

Section: Pk/pd and Toxicitymentioning

confidence: 99%

PK/PD of Oxazolidinones

Theuretzbacher

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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Linezolid, the fi rst available compound in the group of oxazolidinones, provides an effective alternative for the treatment of multidrug-resistant (MDR) Gram-positive bacteria. Linezolid's iv and oral availability expands its usage to the outpatient setting. In vitro, animal, and clinical studies have defi ned an appropriate PK/PD index for linezolid, its correlation with the dosage regimen, and clinical outcome. Due to linezolid's wide interpatient variability, some patients may have increased risk of inadequate drug exposure. As these patients are not readily identifi ed, therapeutic drug monitoring may be necessary for critically ill patient populations as well as in long-term treatment. As alternative antibiotics are scarce, resistance development requires special attention. The selection of linezolid resistant mutants, especially with enterococci, and the emergence of mobile resistance determinants that affect a wide range of other ribosome-targeting antibiotics, will most likely spur the emergence and spread of linezolid resistance. Increasing drug exposure in an attempt to reduce selection pressure may not be feasible due to concentration dependent toxicity. On the other hand, combination therapy may positively impact exposure/resistance relationship, but our knowledge in this area remains incomplete. Employing PK/PD models to defi ne dosing strategies and using antibiotic combinations to reduce selection pressure on linezolid-resistant mutants are major tasks yet to be undertaken.

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Association of Linezolid With Risk of Serotonin Syndrome in Patients Receiving Antidepressants

et al. 2022

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ImportanceLinezolid has the potential to interact with some antidepressants, leading to serotonin syndrome. However, few empirical data support warnings for patients taking antidepressants to avoid linezolid.ObjectivesTo examine the incidence of serotonin syndrome in patients receiving oral linezolid and how concomitant antidepressant treatment changes this risk.Design, Setting, and ParticipantsThis population-based, retrospective cohort study used linked administrative databases at ICES to collect data from outpatients 66 years or older in Ontario, Canada, who were prescribed oral linezolid for any duration from October 1, 2014, to January 1, 2021, with follow-up to 30 days (January 31, 2021).ExposuresThe use of antidepressants while receiving linezolid therapy vs no antidepressant use while receiving linezolid therapy.Main Outcomes and MeasuresThe primary outcome was clinically significant serotonin syndrome based on a physician diagnosis, Sternbach criteria, or the Hunter Serotonin Toxicity Criteria within 30 days of starting oral linezolid treatment. Secondary outcomes were altered mental status, hospitalization, or death within 30 days of starting linezolid treatment.ResultsThe study included 1134 patients (age ranges, 66-69 years for 225 patients [19.8%], 70-79 years for 473 patients [41.7%], and ≥80 years for 436 patients [38.4%]; 595 [52.5%] male) who were prescribed linezolid. Of 1134 patients, 215 (19.0%) were also taking antidepressants. Serotonin syndrome occurred in fewer than 6 patients (&lt;0.5%). The number of serotonin syndrome cases were fewer in the antidepressant group. In a propensity score–matched cohort, the adjusted risk difference for serotonin syndrome between the antidepressant group and the no antidepressant group was −1.2% (95% CI, −2.9% to 0.5%). There were similar rates of altered mental status, hospitalization, and death between the propensity score–matched groups.Conclusions and RelevanceIn this cohort study of older patients who were prescribed linezolid, serotonin syndrome occurred rarely. Concurrent antidepressants did not significantly increase the risk of serotonin syndrome. These findings suggested that linezolid is likely safe for patients receiving antidepressants. Nevertheless, prescribers should remain vigilant for this potential drug interaction.

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Clinical Relevance of Linezolid-Associated Serotonin Toxicity

Cited by 50 publications

References 34 publications

Psychiatric Emergencies

Psychiatric Emergencies

PK/PD of Oxazolidinones

Association of Linezolid With Risk of Serotonin Syndrome in Patients Receiving Antidepressants

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