Sertraline and Rasagiline: 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
Rasagiline
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.
These two medicines should not be taken together. Rasagiline (Azilect) is an MAOI used for Parkinson's disease, and sertraline is an antidepressant that raises serotonin. When you combine them, serotonin can climb too high in your body, which can trigger a dangerous reaction called serotonin syndrome.
Warning signs include a racing heart, high blood pressure, fever, sweating, shaking, muscle twitching, agitation, or confusion. This can become serious very quickly. The good news is that this is very preventable. Your care team knows to keep these apart, including waiting about 2 weeks when switching between them. Never start, stop, or change either drug on your own, and call your doctor or pharmacist with any questions.
Contraindicated combination. Rasagiline is a MAO-B inhibitor (loses selectivity at higher exposure) and sertraline is an SSRI. Concurrent use produces additive serotonergic activity, with reduced MAO-mediated serotonin metabolism increasing synaptic serotonin and the risk of serotonin syndrome or CNS/hypertensive toxicity.
- Direction: additive/potentiated serotonergic effect (increased effect), not a prodrug interaction.
- Evidence: probable; serious and fatal reactions reported.
- Management: avoid co-administration. Allow at least 14 days between discontinuing one and starting the other.
- Monitor for: hyperthermia, autonomic instability, hypertension, tachycardia, myoclonus, hyperreflexia, tremor, altered mental status.
What happens
An increased risk of serotonin syndrome (hypertension, tachycardia, hyperthermia, myoclonus, mental status changes) or CNS toxicity
Interaction Deep Dive
Taking sertraline together with an MAOI is contraindicated. If an MAOI used for treating psychiatric conditions is stopped, allow a minimum of 14 days before starting sertraline. Likewise, once sertraline is stopped, wait at least 14 days before beginning an MAOI prescribed for psychiatric conditions1. Giving sertraline and an MAOI inhibitor at the same time, or with overlapping courses of therapy, can produce CNS toxicity or serotonin syndrome, a hyperserotonergic condition marked by features including restlessness, myoclonus, altered mental status, hyperreflexia, diaphoresis, shivering, and tremor. Reactions that are serious and even fatal have been documented 3465.
Why it happens (mechanism)
Additive serotonergic effects; inhibition of serotonin metabolism by monoamine oxidase
How to manage this interaction
These drugs are not used together. Because the combination can cause serotonin syndrome, your care team avoids overlapping them and manages the switch carefully.
- Keep taking exactly what your prescriber has ordered, and do not start or stop either drug on your own.
- When switching between them, your team will build in a waiting period of at least 14 days so one drug clears before the other begins.
- Make sure any doctor or pharmacist knows you take (or recently took) both.
- Seek urgent care if you notice fever, fast heartbeat, sweating, shaking, muscle twitching, or confusion.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) Taking serotonin specific reuptake inhibitors together with monoamine oxidase inhibitors may result in a toxic condition referred to as serotonin syndrome 2.
b) A 26 year old woman who had used isocarboxazid for eight weeks discontinued the medication for 11 days before starting sertraline. Following a single 100 mg dose of sertraline, she became restless and experienced leg twitches. She was subsequently brought to the emergency room presenting with diaphoresis, tachycardia, hyperreflexia, and a range of neuromuscular disturbances. She showed no improvement following treatment with diazepam and propranolol. She was then administered two 4 mg doses of cyproheptadine one hour apart, with marked improvement in symptoms after the second dose 3.
c) An interaction was reported in a 61 year old woman when sertraline 100 mg twice daily was added to a regimen consisting of lithium, phenelzine, thioridazine, and doxepin. Three hours after her first sertraline dose, she was discovered in a semicomatose state, with raised body temperature, increased pulse, increased respiratory rate, and a blood pressure of 140/110 mmHg. After being taken to the hospital, she was initially misdiagnosed with neuroleptic malignant syndrome (NMS), a diagnosis that was later revised to serotonin syndrome resulting from an interaction between sertraline and phenelzine. The authors recommend that MAO inhibitor treatment be stopped for at least two weeks before starting a selective serotonin reuptake inhibitor (SSRI), and that before beginning a MAOI, SSRI treatment be stopped for at least 5 half-lives of the parent drug and any active metabolites 4.
d) Two case reports pointed to a possible interaction between FLUoxetine and selegiline. In one case, a first episode of mania was noted roughly 1 month after selegiline was added to fluoxetine therapy. The patient improved 2 months after both medications were stopped, and no additional details were given. The second case involved diaphoresis, vasoconstriction, and cyanosis of the hands occurring in close temporal association with the addition of FLUoxetine and selegiline. Both drugs were stopped, with relatively rapid resolution of symptoms. Rechallenge with FLUoxetine alone proceeded without incident 5.
Common questions
Can I take Sertraline and Rasagiline together?
Rasagiline and sertraline should not be taken together because of a serious, potentially fatal serotonin syndrome risk; your care team will keep them apart and allow at least 14 days between them when switching. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Rasagiline 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 Rasagiline interaction managed?
These drugs are not used together. Because the combination can cause serotonin syndrome, your care team avoids overlapping them and manages the switch carefully. Keep taking exactly what your prescriber has ordered, and do not start or stop either drug on your own. When switching between them, your team will build in a waiting period of at least 14 days so one drug clears before the other begins.… 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 Rasagiline 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 (6)
- Product Information: ZOLOFT oral tablets, oral solution, sertraline hydrochloride oral tablets, oral solution. Viatris Specialty LLC (per FDA), Morgantown, WV, 2023. DailyMed
- Sternbach H: The serotonin syndrome. Am J Psychiatr 1991; 148:705-713. PubMed
- Lappin RI & Auchincloss EL: Treatment of the serotonin syndrome with cyproheptadine. N Engl J Med 1994; 331:1021-1022. PubMed
- Graber MA, Hoehns TB, & Perry PJ: Sertraline-phenelzine drug interaction: a serotonin syndrome reaction. Ann Pharmacother 1994; 28:732-735. DOI
- Suchowersky O & de Vries JD: Interaction of fluoxetine and selegiline (letter). Can J Psychiatry 1990; 35:571-572. PubMed
- Bhatara VS & Bandettini FC: Possible interaction between sertraline and tranylcypromine. Clin Pharm 1993; 12:222-225.
Keep reading about Rasagiline
Keep reading about Sertraline
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