From the Guidelines
Linezolid should be avoided in patients taking SSRIs due to the risk of serotonin syndrome, a potentially life-threatening drug interaction. The use of linezolid in patients taking selective serotonin reuptake inhibitors (SSRIs) is associated with a significant risk of serotonin syndrome, as noted in studies 1. If linezolid treatment is absolutely necessary in a patient on an SSRI, the SSRI should ideally be discontinued at least 2 weeks before starting linezolid (5 weeks for fluoxetine due to its longer half-life) to minimize this risk.
Key considerations for managing this interaction include:
- Close monitoring for signs of serotonin syndrome, including mental status changes, neuromuscular abnormalities, and autonomic instability, if the SSRI cannot be stopped and linezolid must be used.
- Consultation with psychiatry and infectious disease specialists is recommended to manage this drug interaction and potentially consider alternative antibiotics if the patient's psychiatric condition requires continued SSRI therapy.
- The interaction between linezolid and SSRIs occurs because linezolid is a monoamine oxidase inhibitor (MAOI) that, when combined with SSRIs, can lead to excessive serotonin levels in the central nervous system, as discussed in 1.
Given the potential for serious adverse effects, the decision to use linezolid in a patient taking an SSRI should be made with caution and only after considering alternative treatment options. The most recent and highest quality evidence, such as that from 1, emphasizes the importance of careful patient management and monitoring when linezolid and SSRIs are used concomitantly.
From the FDA Drug Label
Linezolid should not be administered to patients with carcinoid syndrome and/or patients taking any of the following medications: serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone Potential Serotonergic Interactions Unless patients are carefully observed for signs and/or symptoms of serotonin syndrome, linezolid should not be administered to patients... taking any of the following medications: serotonin re-uptake inhibitors
- Contraindication: The use of linezolid is contraindicated in patients taking Selective Serotonin Reuptake Inhibitors (SSRIs) due to the risk of serotonin syndrome.
- Key consideration: Patients taking SSRIs should not be administered linezolid unless they are carefully observed for signs and/or symptoms of serotonin syndrome 2.
From the Research
Contraindications of Using Linezolid with SSRIs
- The use of linezolid in patients taking Selective Serotonin Reuptake Inhibitors (SSRIs) may lead to serotonin syndrome, a potentially life-threatening condition 3, 4, 5, 6, 7.
- Studies have reported cases of serotonin syndrome in patients taking linezolid and SSRIs, including sertraline, paroxetine, citalopram, and fluoxetine 3.
- The incidence of serotonin syndrome with combined use of linezolid and SSRIs is low, with one study reporting an incidence of 1.1% in patients receiving combination therapy 4.
- Another study found that concurrent antidepressants did not significantly increase the risk of serotonin syndrome in patients taking linezolid 5.
- A systematic review of 84 studies found a low prevalence of serotonin toxicity in both linezolid monotherapy and linezolid concurrent with other serotonergic agents, with symptom resolution occurring in all cases that discontinued linezolid and serotonergic agents 7.
Precautions and Recommendations
- Caution should be used when linezolid is used in patients receiving an SSRI, and other antibiotic options should be considered first 3.
- If the infection requires linezolid, the SSRI should be discontinued, and the patient should be monitored closely for serotonin syndrome 3.
- Prescribers should remain vigilant for the potential drug interaction between linezolid and SSRIs, and close monitoring for symptoms of serotonin syndrome should be considered in patients taking combination therapy 5, 6.