Sertraline and Metaxalone: 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
Metaxalone
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.
Both of these medicines can raise serotonin, a chemical messenger in your body. Sertraline (an antidepressant) does this on purpose, and metaxalone (a muscle relaxer, brand name Skelaxin) can also add to it. When you take them together, that extra serotonin can sometimes build up too much and cause a problem called serotonin syndrome.
Warning signs to watch for include feeling agitated or confused, a fast heartbeat, sweating, shivering, muscle twitching or stiffness, and stomach upset. This is not common and is more of a theoretical concern, but it is worth knowing. The good news is your care team can manage this safely by watching you closely, especially when you first start or change a dose. Please talk with your pharmacist or doctor before making any changes.
Interaction: Additive serotonergic effects with concomitant metaxalone and sertraline (an SSRI), increasing the theoretical risk of serotonin syndrome.
- Mechanism: Pharmacodynamic additive serotonergic activity (neither agent's metabolism drives this interaction).
- Direction: Additive serotonergic burden; risk highest at initiation and dose escalation.
- Onset: Typically several hours to a few days, occasionally later.
- Evidence: Theoretical; case reports at usual therapeutic metaxalone doses.
- Management: Careful clinical observation; monitor for mental status changes, autonomic instability, neuromuscular abnormalities (clonus, hyperreflexia, rigidity), and GI symptoms. Dose may need individualization by the care team.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
When metaxalone (at doses within the standard therapeutic range) is taken together with serotonergic drugs, cases of serotonin syndrome have been documented. Manifestations including altered mental status, autonomic instability, neuromuscular abnormalities, and gastrointestinal symptoms generally appear within several hours up to a few days, though onset can also happen later. If this combination cannot be avoided, close monitoring is advised, especially when therapy is being started and when doses are being adjusted1.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This interaction can usually be managed with attention and monitoring.
- Your care team may watch you more closely, especially when you first start these together or when a dose is changed.
- Doses may need to be adjusted and individualized by your care team.
- Learn the warning signs of serotonin syndrome: agitation, confusion, fast heartbeat, high blood pressure, sweating, shivering, muscle twitching or stiffness, and nausea or diarrhea.
- Seek prompt medical attention if these symptoms appear, and ask your pharmacist or doctor any questions before changing anything.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Cases of serotonin syndrome have been documented when metaxalone (administered at doses within the standard therapeutic range) was used together with serotonergic agents 1.
Common questions
Can I take Sertraline and Metaxalone together?
Taking metaxalone with sertraline can add up to raise serotonin and, rarely, cause serotonin syndrome. Keep taking both as prescribed, know the warning signs, and let your care team monitor you, especially when starting or adjusting a dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Metaxalone interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
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 Metaxalone interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This interaction can usually be managed with attention and monitoring. Your care team may watch you more closely, especially when you first start these together or when a dose is changed. Doses may need to be adjusted and individualized by your care team. Learn the warning signs of serotonin syndrome: agitation, c… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
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 Metaxalone 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 (1)
- Product Information: SKELAXIN(R) oral tablets, metaxalone oral tablets. King Pharmaceuticals, Inc. (per FDA), Bristol, TN, 2018. DailyMed
Keep reading about Metaxalone
Keep reading about Sertraline
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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