Sertraline and Toloxatone: 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 recordToloxatone
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. Sertraline is an antidepressant that raises serotonin, a brain chemical that affects mood. Toloxatone is a type of antidepressant called an MAO inhibitor, which slows down how your body breaks serotonin down. When you combine them, serotonin can build up too high and cause a dangerous reaction called serotonin syndrome.
Warning signs include restlessness, shivering, sweating, muscle twitching, a fast heartbeat, fever, and confusion. This can come on quickly and can be serious. Please do not start or stop either drug on your own. Your doctor or pharmacist can help you switch safely, which usually means leaving a gap of about two weeks between the two.
Contraindicated combination. Sertraline (SSRI) increases synaptic serotonin, while toloxatone inhibits monoamine oxidase, reducing serotonin breakdown. The additive hyperserotonergic effect can precipitate serotonin syndrome or CNS toxicity: hypertension, hyperthermia, myoclonus, hyperreflexia, diaphoresis, tremor, and altered mental status.
- Direction: increased serotonergic effect (both agents active drugs, not prodrugs).
- Onset: rapid; Evidence: probable. Serious/fatal reactions reported with SSRI + MAOI.
- Toloxatone is a reversible, selective MAO-A inhibitor and may pose lower risk than irreversible MAOIs, but coadministration remains contraindicated.
- Management: allow a 14-day washout in either direction before switching.
What happens
CNS toxicity or serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Deep Dive
Giving sertraline together with, or in overlapping fashion alongside, a monoamine oxidase (MAO) inhibitor can lead to CNS toxicity or serotonin syndrome, a hyperserotonergic condition marked by manifestations including restlessness, myoclonus, altered mental status, hyperreflexia, diaphoresis, shivering, and tremor. Combining serotonin specific reuptake inhibitors with MAO inhibitors has been associated with severe and even fatal reactions52364. Because toloxatone is a reversible and selective monoamine oxidase inhibitor, it may not enhance the actions of selective serotonin reuptake inhibitors with the same frequency, magnitude, and duration seen with other MAOIs. Nevertheless, concurrent use remains contraindicated pending additional studies that establish the safety and efficacy of this combination.
Why it happens (mechanism)
Inhibition of serotonin metabolism by monoamine oxidase
How to manage this interaction
This pairing is not used together. The safe approach your care team uses is a washout period between the two drugs.
- Allow at least 14 days after stopping the MAO inhibitor (toloxatone) before starting sertraline.
- Allow at least 14 days after stopping sertraline before starting toloxatone.
- Do not start, stop, or overlap these medicines on your own.
- Tell your pharmacist or prescriber about every antidepressant you take so they can plan the switch and watch for symptoms like agitation, sweating, shivering, muscle twitching, or fever.
Seek urgent care if these symptoms appear.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) Taking SSRIs together with monoamine oxidase inhibitors can bring about a toxic response called serotonin syndrome 1. This syndrome represents excessive serotonergic stimulation and presents with agitation, myoclonus, altered mental status, hyperreflexia, sweating, shivering, and tremor. Death may occur if the condition is not identified and managed properly.
b) A 26-year old woman who had used isocarboxazid for eight weeks discontinued it for 11 days prior to starting sertraline. Following one 100 mg dose of sertraline, she became agitated and experienced leg twitching. She was subsequently brought to the emergency room presenting with sweating, tachycardia, hyperreflexia, and assorted neuromuscular abnormalities. Treatment with diazepam and propranolol produced no improvement. She was then administered two 4 mg doses of cyproheptadine one hour apart, and her symptoms markedly improved after the second dose 2.
c) An interaction was described 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 following the first sertraline dose, she was discovered semicomatose, with raised body temperature, elevated pulse, increased respiratory rate, and a blood pressure of 140/110 mm Hg. Upon arrival at the hospital, she was initially misdiagnosed with neuroleptic malignant syndrome (NMS), a diagnosis later revised to serotonin syndrome resulting from an interaction between sertraline and phenelzine. The authors recommend that monoamine oxidase inhibitor (MAOI) therapy be stopped for at least two weeks before starting a selective serotonin reuptake inhibitor (SSRI), and that prior to beginning a MAOI, SSRI therapy be stopped for at least five half-lives of the parent drug and any active metabolites 3.
d) Two case reports pointed to a potential interaction between fluoxetine and selegiline 4. In one case, a first episode of mania was noted roughly one month after selegiline was added to fluoxetine. The patient recovered two months after both agents were stopped, and no additional information was given. In the second case, sweating, vasoconstriction, and cyanosis of the hands developed in close temporal association with the addition of fluoxetine to selegiline. Both medications were discontinued, and the symptoms resolved relatively rapidly. A rechallenge with fluoxetine alone proceeded without incident.
Common questions
Can I take Sertraline and Toloxatone together?
Sertraline and toloxatone should not be used together because the combination can cause serotonin syndrome; your care team will separate them with at least a 14-day gap in either direction. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Toloxatone interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Sertraline and Toloxatone interaction managed?
This pairing is not used together. The safe approach your care team uses is a washout period between the two drugs. Allow at least 14 days after stopping the MAO inhibitor (toloxatone) before starting sertraline. Allow at least 14 days after stopping sertraline before starting toloxatone. Do not start, stop, or overlap these medicines on your own. Tell your pharmacist or prescriber about every ant… 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 Toloxatone 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)
- 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
- Product Information: Zoloft(R), sertraline hydrochloride. Roerig Division of Pfizer Inc, New York, NY, 1999. DailyMed
- Bhatara VS & Bandettini FC: Possible interaction between sertraline and tranylcypromine. Clin Pharm 1993; 12:222-225.
Keep reading about Sertraline
Keep reading about Toloxatone
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