The antibiotic linezolid is an MAOI, and its label warns of fatal serotonin syndrome with antidepressants
Zyvox's label: "Spontaneous reports of serotonin syndrome including fatal cases associated with the concomitant use of ZYVOX and serotonergic agents have been reported." It is not to be used with an MAOI or within two weeks of one.
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: Spontaneous reports cannot give a rate. The label lists triptans among serotonergic agents; the Orlova 2018 row in this wave measured the triptan plus SSRI combination and found it rare.
An antibiotic prescribed for a skin or lung infection can interact with an antidepressant because it happens to share a mechanism with the oldest antidepressant class.
Significant findings
ZYVOX (linezolid) prescribing information (Pfizer, July 2026), section 4.2: "Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g., phenelzine, isocarboxazid) or within two weeks of taking any such medicinal product."
Section 5.3, Serotonin Syndrome: "Spontaneous reports of serotonin syndrome including fatal cases associated with the concomitant use of ZYVOX and serotonergic agents have been reported. Commonly used serotonergic agents include serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, buspirone, serotonin 5-HT1 receptor agonists (triptans), and opioids, including meperidine."
The symptom list, verbatim: "Symptoms associated with serotonin syndrome may include hyperthermia, diaphoresis, agitation, hyperreflexia, clonus, pyrexia, opsoclonus, muscle rigidity, tremor, and hypertonia." The instruction: "Monitor patients for the emergence of serotonin syndrome with the concomitant use of ZYVOX and serotonergic agents ... If signs or symptoms of serotonin syndrome occur, consider discontinuing ZYVOX and/or concomitant serotonergic agents as clinically appropriate and initiate supportive treatment."
Section 5.6 adds a blood pressure warning with decongestants and stimulants: linezolid should not be given, unless blood pressure is monitored, to patients taking "directly and indirectly acting sympathomimetic agents (e.g., pseudoephedrine)".
Worth asking
The interaction is easy to miss because the two prescriptions come from different doctors for unrelated problems. If you take an SSRI, an SNRI, a tricyclic, buspirone or a triptan and are prescribed linezolid, ask whether the prescriber knows, and whether an alternative antibiotic would do. The FDA's 2011 notice on this interaction found most reported cases involved an SSRI or SNRI; that notice is no longer hosted, but the label carries its content. The Hunter criteria row in this wave describes how serotonin toxicity is diagnosed.
Source
ZYVOX (linezolid): FDA-approved prescribing information, Contraindications 4.2, Warnings and Precautions 5.3 and 5.6 — Pharmacia & Upjohn Company LLC (Pfizer); US Food and Drug Administration (2026)
Regulator or national health body
How this was scored
- Study design
- Regulatory safety determination
- Funding
- Industry funded
- Published in
- Regulator or national health body
- Sample size
- not recorded
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 57 out of 100 on our published rubric. One caveat travels with that badge: Spontaneous reports cannot give a rate. The label lists triptans among serotonergic agents; the Orlova 2018 row in this wave measured the triptan plus SSRI combination and found it rare. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
ZYVOX (linezolid): FDA-approved prescribing information, Contraindications 4.2, Warnings and Precautions 5.3 and 5.6 — Pharmacia & Upjohn Company LLC (Pfizer); US Food and Drug Administration (2026). Published in: Regulator or national health body. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Regulatory safety determination. Funding: Industry funded. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.