Sertraline and Safinamide: 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
Safinamide
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.
Safinamide (Xadago) is a Parkinson's medicine that works as a type of MAO inhibitor, and sertraline is an antidepressant that raises serotonin levels in your brain. When you take them together, both push serotonin up at the same time. That can lead to a dangerous reaction called serotonin syndrome, which can cause high blood pressure, a racing heart, fever, muscle twitching, sweating, and confusion.
Because of this risk, these two drugs are generally not used together. Please don't stop or change either medicine on your own. Instead, talk with your doctor or pharmacist, who can review your medicines and choose a safe plan for you.
Contraindicated combination. Safinamide is a selective MAO-B inhibitor; sertraline is an SSRI. Concurrent use produces additive serotonergic activity, raising the risk of serotonin syndrome (hypertension, tachycardia, hyperthermia, myoclonus, altered mental status).
- Mechanism: pharmacodynamic (additive serotonergic effect); neither drug is a prodrug requiring activation.
- Evidence: theoretical, though a serotonin syndrome case with an MAO-B inhibitor plus an SSRI occurred in trials.
- Onset: unspecified.
- Management: avoid coadministration. Observe a 14-day washout in either direction. If unavoidable, use the lowest effective sertraline dose and monitor closely for serotonergic toxicity.
What happens
An increased risk of serotonin syndrome (hypertension, tachycardia, hyperthermia, myoclonus, mental status changes)
Interaction Deep Dive
The combined administration of sertraline with safinamide (a monoamine oxidase inhibitor) is contraindicated. If an MAOI prescribed for psychiatric conditions is stopped, allow a minimum of 14 days before beginning sertraline. Likewise, after sertraline is discontinued, wait no less than 14 days before starting an MAOI intended for psychiatric disorders1. During clinical trials, one patient experienced serotonin syndrome when safinamide (an MAO type B inhibitor) was taken together with an SSRI. Should the two agents be given together, watch for signs of serotonin syndrome and administer sertraline at the lowest effective dose2.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
These two are generally not combined. Keep taking your medicines exactly as prescribed and do not start, stop, or change either one on your own.
- Bring your full medication list to your pharmacist or prescriber so they can review this combination.
- Your care team will usually avoid using them together, and may plan a 14-day gap when switching from one to the other.
- If both are truly needed, your team can use the lowest effective dose of sertraline and monitor you closely.
- Seek urgent care for fever, fast heartbeat, muscle twitching or stiffness, heavy sweating, agitation, or confusion.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) During clinical trials, a patient who was taking safinamide experienced serotonin syndrome when an SSRI was used at the same time 2.
Common questions
Can I take Sertraline and Safinamide together?
Safinamide (an MAO-B inhibitor) and sertraline together can raise serotonin dangerously and are considered a contraindicated pair, so contact your doctor or pharmacist rather than combining them, and get urgent help if you feel feverish, shaky, or confused. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Safinamide 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 Safinamide interaction managed?
These two are generally not combined. Keep taking your medicines exactly as prescribed and do not start, stop, or change either one on your own. Bring your full medication list to your pharmacist or prescriber so they can review this combination. Your care team will usually avoid using them together, and may plan a 14-day gap when switching from one to the other. If both are truly needed, your tea… 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 Safinamide 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 (2)
- Product Information: ZOLOFT oral tablets, oral solution, sertraline hydrochloride oral tablets, oral solution. Viatris Specialty LLC (per FDA), Morgantown, WV, 2023. DailyMed
- Product Information: XADAGO(R) oral tablets, safinamide oral tablets. US WorldMeds, LLC (per FDA), Louisville, KY, 2017. DailyMed
Keep reading about Safinamide
Keep reading about Sertraline
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