Sertraline and Iproniazid: 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 recordIproniazid
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. Iproniazid is an older type of antidepressant called an MAO inhibitor that also raises serotonin, but in a different way. When you combine them, serotonin can climb too high and cause a dangerous reaction called serotonin syndrome. This can bring on restlessness, shivering, muscle twitching, sweating, a racing heart, high fever, and confusion. It can come on fast and can be very serious.
The good news is this is easy to avoid. Your care team will make sure the two are never used at the same time, and they will leave a safe gap between them.
Contraindicated combination. Sertraline (SSRI) plus iproniazid (nonselective MAO inhibitor) produces additive/synergistic serotonergic activity. MAO inhibition blocks serotonin metabolism while sertraline blocks reuptake, driving a hyperserotonergic state.
- Effect: serotonin syndrome / CNS toxicity (hypertension, hyperthermia, myoclonus, hyperreflexia, diaphoresis, altered mental status); potentially fatal.
- Onset: rapid. Evidence: probable.
- Neither drug is a prodrug; interaction is pharmacodynamic, not activation-dependent.
Management: Do not co-administer. Allow >=14 days after stopping the MAOI before starting sertraline, and >=14 days after stopping sertraline before starting an MAOI (longer for fluoxetine, not applicable here).
What happens
CNS toxicity or serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Deep Dive
Giving sertraline together with, or in overlapping courses with, a monoamine oxidase (MAO) inhibitor can produce CNS toxicity or serotonin syndrome, a hyperserotonergic condition marked by signs including restlessness, myoclonus, mental status alterations, hyperreflexia, diaphoresis, shivering, and tremor. Reactions that are serious and sometimes fatal have been documented when serotonin specific reuptake inhibitors are used alongside MAO inhibitors62354. Their combined use is contraindicated.
Why it happens (mechanism)
Inhibition of serotonin metabolism by monoamine oxidase
How to manage this interaction
These drugs are not used together. This combination is contraindicated, so your care team will avoid overlapping them entirely rather than adjusting a dose.
- A washout period is standard: at least 14 days between stopping one and starting the other, in either direction.
- Never start one while still taking the other unless your prescriber has confirmed enough time has passed.
Take any single medicine exactly as prescribed. If you have taken both, or are unsure whether enough time has passed between them, contact your pharmacist or prescriber promptly. Seek urgent care for agitation, fever, shivering, muscle twitching, sweating, or confusion.
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 trigger a toxic response called serotonin syndrome 1. This condition reflects excessive serotonergic stimulation and appears as restlessness, myoclonus, altered mental status, hyperreflexia, diaphoresis, shivering, and tremor. Failure to recognize and appropriately treat the syndrome can lead to death.
b) A 26-year-old woman who had used isocarboxazid for eight weeks discontinued it for 11 days prior to starting sertraline therapy. Following a single 100 mg dose of sertraline, she became restless and experienced leg twitches. She was subsequently brought to the emergency room with diaphoresis, tachycardia, hyperreflexia, and assorted neuromuscular disturbances. She did not respond to treatment with diazepam and propranolol. She then received two 4 mg doses of cyproheptadine given an hour apart, with marked symptom improvement after the second dose 2.
c) An interaction was described in a 61-year-old woman in whom sertraline 100 mg twice daily was added to an existing regimen of lithium, phenelzine, thioridazine, and doxepin. Three hours after her first sertraline dose, she was found semicomatose, with raised body temperature, elevated pulse, increased respiratory rate, and a blood pressure of 140/110 mm Hg. Once she reached 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 before beginning a MAOI, SSRI therapy be halted for at least five half-lives of the parent drug and any active metabolites 3.
d) Two case reports pointed to a possible interaction between fluoxetine and selegiline 4. In one case, a first manic episode was seen roughly one month after selegiline was added to fluoxetine. The patient improved two months after discontinuing both drugs, and no additional details were given. In the second case, diaphoresis, vasoconstriction, and cyanosis of the hands developed in close temporal association with adding fluoxetine to selegiline. Both agents were stopped, with relatively rapid resolution of symptoms. Rechallenge with fluoxetine alone proceeded without incident.
Common questions
Can I take Sertraline and Iproniazid together?
Sertraline and iproniazid must never be used together because they can cause life-threatening serotonin syndrome; a gap of at least 14 days is required when switching between them. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Iproniazid 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 Iproniazid interaction managed?
These drugs are not used together. This combination is contraindicated, so your care team will avoid overlapping them entirely rather than adjusting a dose. A washout period is standard: at least 14 days between stopping one and starting the other, in either direction. Never start one while still taking the other unless your prescriber has confirmed enough time has passed. Take any single medicine… 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 Iproniazid 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
- Bhatara VS & Bandettini FC: Possible interaction between sertraline and tranylcypromine. Clin Pharm 1993; 12:222-225.
- Product Information: Zoloft(R), sertraline hydrochloride. Roerig Division of Pfizer Inc, New York, NY, 1999. DailyMed
Keep reading about Sertraline
Keep reading about Iproniazid
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