Sertraline and Linezolid: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Linezolid
Sertraline
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Linezolid (Zyvox) is an antibiotic that also acts like an older type of antidepressant called an MAOI. Sertraline raises serotonin, a brain chemical. Taken together, they can push serotonin too high and cause serotonin syndrome. Warning signs include a fast heartbeat, high blood pressure, fever, sweating, shakiness or muscle twitching, agitation, and confusion.
Because of this risk, these two drugs are generally not used at the same time. The good news is your care team knows how to handle this safely by spacing the medicines apart or picking a different option. Please don't stop or change anything on your own. Just talk with your doctor or pharmacist.
Interaction: Additive serotonergic effects. Linezolid is a reversible, nonselective MAO inhibitor; combined with the SSRI sertraline, serotonergic tone increases, raising the risk of serotonin syndrome (hypertension, tachycardia, hyperthermia, myoclonus, altered mental status).
- Direction: Increased serotonergic effect (pharmacodynamic, not prodrug-related).
- Severity/Evidence: Contraindicated; probable. A retrospective cohort found serotonin syndrome in =14 days after stopping sertraline before an MAOI, and >=14 days after an MAOI before sertraline. If urgent linezolid is required and no alternative exists, discontinue sertraline first, then start linezolid, with monitoring.
What happens
An increased risk of serotonin syndrome (hypertension, tachycardia, hyperthermia, myoclonus, mental status changes)
Interaction Deep Dive
Taking sertraline together with an MAOI such as linezolid is contraindicated. When an MAOI used for psychiatric conditions is stopped, allow a minimum of 14 days before starting sertraline. Likewise, after sertraline is discontinued, wait at least 14 days before beginning an MAOI intended for psychiatric conditions. Should a patient on sertraline require urgent linezolid therapy and no alternatives exist, discontinue sertraline immediately and then give the linezolid1. A retrospective cohort study conducted in older adults found that serotonin syndrome developed in fewer than 0.5% of individuals receiving both linezolid and an antidepressant. Within the propensity score-matched cohort, the risk of serotonin syndrome did not differ between patients taking antidepressants along with linezolid and those not taking antidepressants. Similarly, no difference was seen between the groups in the frequency of altered mental status or confusion, hospitalization, or all-cause death 2.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
These two medicines are generally not given together because of serotonin syndrome risk, but your care team can manage this safely.
- Keep taking both exactly as prescribed until your doctor or pharmacist tells you otherwise. Do not stop either one on your own.
- Your team typically separates these drugs in time, waiting about 14 days between one and the other.
- If you urgently need linezolid and there is no substitute, your prescriber may stop sertraline first and then start the antibiotic, watching you closely.
- Get help right away for fever, fast heartbeat, sweating, muscle twitching, agitation, or confusion.
Ask your pharmacist to review all your medicines whenever linezolid is prescribed.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) A retrospective cohort study involving older adults given oral linezolid 600 mg twice daily (N=1134) found that serotonin syndrome developed in fewer than 6 patients (under 0.5%) among those also receiving an antidepressant (n=215). Within the propensity score-matched cohort (n=332), the risk of clinically significant serotonin syndrome did not differ between patients taking both antidepressants and linezolid versus those on linezolid alone (adjusted risk difference, -1.2%; 95% CI, -2.9% to 0.5%). Likewise, there was no difference between groups in the frequency of altered mental status or confusion, hospitalization, or all-cause death. Participants were 66 years of age or older, and among those on an antidepressant, 47.9% used an SSRI, 16.7% used an SNRI, 7% used a tricyclic antidepressant, 3.3% used a norepinephrine and dopamine reuptake inhibitor, and none used an MAOI 2.
b) Serotonin syndrome was documented in a 47-year-old woman on 2 separate occasions after linezolid 600 mg twice daily was added to her drug regimen (which included sertraline 100 mg daily) to treat a stump wound infection following an above the knee amputation. During the first episode, confusion, hypertension, and incoordination appeared on day 4 of linezolid therapy; these symptoms resolved 4 days after vancomycin replaced linezolid. During the second episode, delirium, confusion, myoclonus, and incoordination emerged on day 9 of linezolid therapy even though sertraline had been stopped on day 1; cardiopulmonary arrest occurred, together with diarrhea and tachycardia, leaving the patient comatose with an anoxic brain injury. Linezolid was stopped and cyproheptadine (a serotonin antagonist) was begun, and the tachycardia and diarrhea resolved within 4 days. The patient later died after failing to recover from the brain injury; the ventilator and dialysis were discontinued 3.
c) A case of serotonin syndrome arose in a patient prescribed linezolid and sertraline. A 45-year-old man with a history of schizoaffective disorder was admitted to the trauma service following an acute suicide attempt that caused a T6 level spinal cord injury and paraplegia. Treatment with sertraline (200 mg daily) and risperiDONE (1 mg twice daily) was started after he was diagnosed with acute depression and psychosis. BuPROPion 75 mg twice daily, traZODone 50 mg every evening, and lithium 300 mg twice daily were subsequently added to his regimen. He underwent sacral flap closure with a bilateral gluteal myocutaneous flap and then developed a deep sacral decubitus ulcer. His temperature and WBC count stayed elevated for several days. A culture of the ulcer identified a vancomycin-resistant Enterococcus faecalis. He was started on linezolid 600 mg IV every 12 hours and metroNIDAZOLE 500 mg every 6 hours. Lithium was stopped after his lithium level was found to be elevated at 1.1 mEq/L. Ten days after linezolid was initiated, the patient reported worsening tremor, nausea, vomiting, diarrhea, and dry mouth. Sertraline, buPROPion, and traZODone were discontinued. His concurrent medications included baclofen, promethazine, docusate sodium, bisacodyl, megestrol, lansoprazole, and risperiDONE. On the next day, the patient became delirious with acute confusion, visual hallucinations, and delusions. His temperature rose to 100.1 degrees F, pulse 101, respirations 20/min, and blood pressure 100/71 mmHg. He exhibited coarse tremor and myoclonus. His pupils were dilated to 6 mm and minimally reactive. A diagnosis of serotonin syndrome was considered. The serotonin syndrome symptoms resolved with cyproheptadine treatment 4.
d) In one case report, a 36-year-old man developed symptoms of serotonin syndrome after concurrent treatment with linezolid and sertraline. The patient had undergone an allogeneic stem cell transplant following high-dose cycloPHOSphamide, total body irradiation, and antithymocyte globulin. His recovery was complicated by severe hemorrhagic cystitis, steroid-refractory graft-versus-host disease, thrombotic thrombocytic purpura, renal failure, and multiple pulmonary infections. On day 137, the patient was given linezolid 600 mg IV every 12 hours. His current medications included tacrolimus, corticosteroids, thalidomide 100 mg daily, sertraline 50 mg daily, morphine, and ALPRAZolam. On day 5 of linezolid therapy, the patient experienced confusion, restlessness, delirium, and agitation. He developed hypertension and a high fever (40 degrees C). His WBC and platelet counts began to fall considerably. On day 6 of therapy, all medications with neurological effects were discontinued, including sertraline, thalidomide, ALPRAZolam, and morphine. The patient's symptoms subsided within a day. Thalidomide, ALPRAZolam, and morphine were restarted with no recurrence of symptoms 5.
Common questions
Can I take Sertraline and Linezolid together?
Linezolid acts as an MAOI and combining it with sertraline can trigger serotonin syndrome, so the two are contraindicated together; your care team will separate them in time or choose an alternative. Keep taking your medicines as prescribed and check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Linezolid interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Sertraline and Linezolid interaction managed?
These two medicines are generally not given together because of serotonin syndrome risk, but your care team can manage this safely. Keep taking both exactly as prescribed until your doctor or pharmacist tells you otherwise. Do not stop either one on your own. Your team typically separates these drugs in time, waiting about 14 days between one and the other. If you urgently need linezolid and there… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Sertraline or Linezolid need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (5)
- Product Information: ZOLOFT oral tablets, oral solution, sertraline hydrochloride oral tablets, oral solution. Viatris Specialty LLC (per FDA), Morgantown, WV, 2023. DailyMed
- Bai AD, McKenna S, Wise H, et al: Association of linezolid with risk of serotonin syndrome in patients receiving antidepressants. JAMA Netw Open 2022; 5(12):e2247426. PubMed
- Clark DB, Andrus MR, & Byrd DC: Drug interactions between linezolid and selective serotonin reuptake inhibitors: case report involving sertraline and review of the literature. Pharmacotherapy 2006; 26(2):269-276. PubMed
- Lavery S, Ravi H, McDaniel W, et al: Linezolid and serotonin syndrome. Psychosomatics 2001; 42(5):432-434. PubMed
- Hachem RY, Hicks K, Huen A, et al: Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients. Clin Infect Dis 2003; 37(1):e8-e11. PubMed
Keep reading about Linezolid
Keep reading about Sertraline
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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