Isocarboxazid and Sertraline: 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
Isocarboxazid
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. Isocarboxazid (Marplan) is an older antidepressant called an MAOI, and sertraline is an SSRI antidepressant. Both raise the level of a brain chemical called serotonin. When you combine them, serotonin can climb too high and cause a dangerous reaction called serotonin syndrome. Warning signs include a racing heart, high blood pressure, fever, sweating, shaking, muscle twitching, agitation, and confusion. This can become serious, so doctors keep these drugs apart.
The good news: your care team knows how to manage this safely, usually by leaving enough time between the two. Never start or stop either one on your own. Talk with your pharmacist or doctor first.
Contraindicated combination. Co-administration of the MAOI isocarboxazid with the SSRI sertraline produces additive serotonergic activity: sertraline increases synaptic serotonin while MAO inhibition blocks its metabolism, risking serotonin syndrome and CNS toxicity.
- Direction: markedly increased serotonergic effect (PD interaction, not prodrug-dependent).
- Presentation: hypertension, tachycardia, hyperthermia, myoclonus, hyperreflexia, diaphoresis, tremor, altered mental status; potentially fatal.
- Evidence: probable.
- Management: avoid concurrent use. Allow at least 14 days after stopping the MAOI before starting sertraline, and at least 14 days after stopping sertraline before starting an MAOI.
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 was being used for psychiatric conditions, allow a minimum of 14 days after stopping it before starting sertraline. Likewise, allow at least 14 days after stopping sertraline before beginning an MAOI intended for psychiatric conditions1. Using these agents at the same time, or having overlapping courses of sertraline and an MAOI inhibitor, can produce CNS toxicity or serotonin syndrome, a hyperserotonergic condition marked by symptoms including restlessness, myoclonus, altered mental status, hyperreflexia, diaphoresis, shivering, and tremor. Reactions that are serious and even fatal have been reported3465.
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. The standard approach is to keep them separated in time rather than overlap them.
- Your care team typically allows at least 14 days between stopping one and starting the other, in either direction.
- Keep taking whichever medicine you are currently prescribed, and do not start or stop either drug on your own.
- Ask your pharmacist or prescriber before any switch so the washout is planned correctly.
- Seek urgent care if you notice a racing heart, fever, sweating, shaking, muscle twitching, agitation, 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 cause a toxic response referred to as serotonin syndrome 2.
b) A 26 year old woman who had taken 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 assorted neuromuscular disturbances. Her condition did not get better after she received diazepam and propranolol. She was then administered two 4 mg doses of cyproheptadine one hour apart, and her symptoms improved markedly after the second dose 3.
c) A drug interaction was described in a 61 year old woman when sertraline 100 mg twice daily was introduced to a regimen consisting of lithium, phenelzine, thioridazine, and doxepin. Three hours after she took the first sertraline dose, she was found 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 incorrectly diagnosed 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 therapy be stopped for at least two weeks prior to starting a selective serotonin reuptake inhibitor (SSRI), and that before beginning a MAOI, SSRI therapy be halted for at least 5 half-lives of the parent drug and any active metabolites 4.
d) Two case reports pointed to a potential interaction between FLUoxetine and selegiline. In the first case, an initial episode of mania was noted roughly 1 month after selegiline was added to fluoxetine therapy. The patient got better 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 relationship to the addition of FLUoxetine and selegiline. Both drugs were discontinued, and the symptoms resolved relatively quickly. Rechallenge with FLUoxetine alone took place without incident 5.
Common questions
Can I take Isocarboxazid and Sertraline together?
Sertraline and isocarboxazid (Marplan) should never be taken together because of the risk of serotonin syndrome; allow at least 14 days between the two, and let your prescriber plan any switch. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Isocarboxazid and Sertraline 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 Isocarboxazid and Sertraline interaction managed?
These drugs are not used together. The standard approach is to keep them separated in time rather than overlap them. Your care team typically allows at least 14 days between stopping one and starting the other, in either direction. Keep taking whichever medicine you are currently prescribed, and do not start or stop either drug on your own. Ask your pharmacist or prescriber before any switch so th… 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 Isocarboxazid or Sertraline 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 Isocarboxazid
Keep reading about Sertraline
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