Maprotiline and Tranylcypromine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Tranylcypromine
Maprotiline
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.
What happens
An increased risk of severe or life threatening reactions, like serotonergic syndrome, neurotoxicity, seizures
Interaction Deep Dive
Concomitant maprotiline (tricyclic antidepressant) and tranylcypromine (MAOI) use has resulted in hyperpyrexia, convulsions, and death12. Concomitant use is contraindicated as it may increase serotonergic syndrome. However, there may be circumstances when treatment with other serotonergic substances is necessary and cannot be delayed. In such cases, discontinue tranylcypromine as soon as possible before initiating treatment with the other agent. Discontinue treatment with tranylcypromine and any concomitant serotonergic agents immediately if adverse events occur, and initiate supportive symptomatic treatment. If initiating maprotiline in a patient currently receiving tranylcypromine, discontinue tranylcypromine and allow at least 1 week to elapse prior to starting maprotiline. Conversely, if initiating tranylcypromine in a patient currently receiving maprotiline, discontinue maprotiline and allow at least 4 to 5 half-lives of maprotiline and any active metabolites to elapse prior to starting tranylcypromine. The potential for interactions persists after discontinuation of tranylcypromine tablets until MAO activity has sufficiently recovered. Inhibition of MAO may persist up to 10 days following discontinuation 3.
Why it happens (mechanism)
Additive serotonergic effects; altered catecholamine uptake and metabolism
Literature reports
1 report — tap to read
a) The development of a potentially life-threatening serotonin syndrome has been reported with MAOIs when used concomitantly with other serotonergic drugs. Manifestations of the serotonin syndrome may include mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia; with possible rapid fluctuations of vital signs), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). Fatal outcome of serotonin syndrome has been reported, including in patients who had been treated with tranylcypromine tablets. In some cases of an interaction between tranylcypromine tablets and SSRIs or SNRIs, the features of the syndrome resembled neuroleptic malignant syndrome 3.
Common questions
Can I take Maprotiline and Tranylcypromine together?
An increased risk of severe or life threatening reactions, like serotonergic syndrome, neurotoxicity, seizures Always confirm with your pharmacist or prescriber before making any change.
How serious is the Maprotiline 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 strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Maprotiline 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 (3)
- Schuckit M, Robins E, & Feighner JP: Tricyclic antidepressants and monoamine oxidase inhibitors. Combination therapy in the treatment of depression. Arch Gen Psychiatry 1971; 24:509-514. PubMed
- White K & Simpson G: The combined use of MAOIs and tricyclics. J Clin Psychiatry 1984; 45:67-69.
- Product Information: Tranylcypromine oral tablets, tranylcypromine oral tablets. Solco Healthcare US, LLC (per DailyMed), Somerset, NJ, 2024. DailyMed
Keep reading about Tranylcypromine
Keep reading about Maprotiline
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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