Sertraline and Tranylcypromine: 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
Sertraline
No brand names on recordTranylcypromine
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. Sertraline (an antidepressant) and tranylcypromine (Parnate, an older antidepressant called an MAOI) both raise serotonin, a brain chemical. When they overlap, serotonin can climb too high and cause a dangerous reaction called serotonin syndrome. Warning signs include agitation, sweating, shivering, muscle twitching, a fast heartbeat, high fever, and confusion. This can become serious, even life-threatening.
The good news is this is completely avoidable. Doctors keep a gap between these drugs on purpose. If you have been prescribed both, or you are switching from one to the other, talk with your pharmacist or doctor right away so they can time it safely.
Contraindicated combination. Concurrent or overlapping sertraline (SSRI) and tranylcypromine (irreversible nonselective MAOI) produces additive serotonergic effects; MAO inhibition blocks serotonin catabolism while the SSRI blocks reuptake, risking serotonin syndrome or CNS toxicity.
- Direction: pharmacodynamic potentiation of serotonergic activity (neither is a prodrug requiring activation).
- Evidence: probable; serious and fatal reactions reported.
- Management: Do not co-administer. Allow at least 14 days after stopping the MAOI before starting sertraline, and at least 14 days after stopping sertraline before starting an MAOI.
- Monitor for hyperthermia, hypertension, tachycardia, myoclonus, hyperreflexia, diaphoresis, and mental status changes if inadvertent overlap occurs.
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. Before starting sertraline, allow a minimum of 14 days to pass following the discontinuation of an MAOI used for psychiatric conditions. Likewise, after stopping sertraline, wait at least 14 days before beginning an MAOI intended for psychiatric disorders1. Overlapping or simultaneous treatment with sertraline and an MAOI inhibitor can produce CNS toxicity or serotonin syndrome, a hyperserotonergic condition marked by manifestations 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
This combination is not used together. The safe approach is a washout period so the drugs never overlap in your body.
- If switching from tranylcypromine (Parnate) to sertraline, your care team will have you wait at least 14 days after stopping the MAOI before starting sertraline.
- If switching from sertraline to tranylcypromine, they will have you wait at least 14 days after stopping sertraline before starting the MAOI.
- Keep taking your current medicine exactly as prescribed, and never start the second one on your own.
- Call your pharmacist or prescriber to plan any switch, and seek urgent care for fever, sweating, shivering, muscle twitching, a racing heart, 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 response 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 prior to 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 assorted 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 her symptoms after the second dose 3.
c) A drug interaction was documented in a 61 year old woman in whom sertraline 100 mg twice daily was added to a regimen consisting of lithium, phenelzine, thioridazine, and doxepin. Three hours after the first sertraline dose, she was discovered in a semicomatose condition, with raised body temperature, elevated pulse, increased respiration rate, and a blood pressure of 140/110 mmHg. Following transfer to the hospital, she was initially misdiagnosed with neuroleptic malignant syndrome (NMS), a diagnosis that was subsequently revised to serotonin syndrome resulting from an interaction between sertraline and phenelzine. The authors recommend that MAO inhibitor therapy be stopped for at least two weeks before starting a selective serotonin reuptake inhibitor (SSRI), and that prior to initiating a MAOI, SSRI therapy 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 discontinued, and symptoms resolved relatively quickly. A rechallenge using FLUoxetine alone proceeded without incident 5.
Common questions
Can I take Sertraline and Tranylcypromine together?
Do not take sertraline and tranylcypromine together; a 14-day gap is required when switching between them. Let your pharmacist or doctor plan the switch, and get urgent help if you notice fever, sweating, tremor, a racing heart, or confusion. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Tranylcypromine 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 Tranylcypromine interaction managed?
This combination is not used together. The safe approach is a washout period so the drugs never overlap in your body. If switching from tranylcypromine (Parnate) to sertraline, your care team will have you wait at least 14 days after stopping the MAOI before starting sertraline. If switching from sertraline to tranylcypromine, they will have you wait at least 14 days after stopping sertraline befo… 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 Tranylcypromine 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 Sertraline
Keep reading about Tranylcypromine
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