From the Guidelines
Trazodone and linezolid should not be used together due to the risk of serotonin syndrome, a potentially life-threatening condition. This is because linezolid is a monoamine oxidase inhibitor (MAOI) and trazodone increases serotonin levels in the brain, creating a dangerous drug interaction that can lead to excessive serotonin accumulation, causing symptoms like agitation, confusion, high fever, muscle rigidity, and seizures 1.
Key Considerations
- The combination of trazodone and linezolid can lead to serious CNS reactions, such as serotonin syndrome or neuroleptic malignant syndrome–like reactions 1.
- If a patient requires linezolid for an infection, trazodone should be discontinued at least 24 hours before starting linezolid therapy to minimize the risk of serotonin syndrome.
- Alternative antidepressants with less serotonergic activity or alternative antibiotics should be considered when possible to avoid this dangerous drug interaction.
- In emergency situations where both medications are deemed necessary, hospitalization with close monitoring is recommended, especially during the first 24-72 hours after starting linezolid or within two weeks of stopping it.
Monitoring and Precautions
- Strict clinical monitoring for potential toxicity, including peripheral neuropathy, optic neuritis, anemia, and leukopenia, is necessary when using linezolid, particularly with long-term use 1.
- Assessment for visual toxicity must continue after restarting linezolid if optic neuritis occurs, and some patients may be rechallenged successfully with linezolid once vision normalizes, potentially at a reduced dose of 300 mg daily 1.
From the FDA Drug Label
In addition, do not initiate Trazodone Hydrochloride Tablets in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Trazodone Hydrochloride Tablets, discontinue Trazodone Hydrochloride Tablets before initiating treatment with the MAOI
The use of trazodone with linezolid is contraindicated due to the risk of serotonin syndrome. Trazodone Hydrochloride Tablets should be discontinued before initiating treatment with linezolid 2.
From the Research
Trazodone and Linezolid Interaction
- The interaction between trazodone and linezolid is a concern due to the potential risk of serotonin syndrome, a potentially fatal increase in serotonergic activity in both the central nervous system and peripheral nervous system 3.
- A case report described a patient who developed serotonin toxicity after receiving linezolid while taking trazodone and citalopram, highlighting the importance of monitoring patients for signs of serotonin syndrome when combining these medications 3.
- Another case report described a patient who developed probable serotonin toxicity after initiation of linezolid, despite recent discontinuation of the SSRI escitalopram, and was concomitantly receiving trazodone and clonazepam 4.
- A systematic review found that the incidence of serotonin toxicity with linezolid monotherapy was 0.0050%, and with linezolid combination therapy was 0.0134%, suggesting a low prevalence of serotonin toxicity in both scenarios 5.
- However, the risk of serotonin syndrome should not be underestimated, and prescribers should remain vigilant for this potential drug interaction, especially when combining linezolid with serotonergic agents like trazodone 6.
Key Findings
- Serotonin syndrome can occur when linezolid is combined with serotonergic agents like trazodone 3, 4.
- The incidence of serotonin toxicity with linezolid is low, but the risk should not be underestimated 5.
- Prescribers should monitor patients for signs of serotonin syndrome when combining linezolid with serotonergic agents like trazodone 6, 3.
- Discontinuation of an SSRI upon initiation of linezolid does not eliminate the risk of serotonin toxicity, and other concomitant medications may worsen or improve some of the symptoms 4.