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Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice.
Other
Tranylcypromine is a potent, non-selective, and irreversible monoamine oxidase inhibitor (MAOI) indicated for the treatment of major depressive disorder (MDD) in adult patients who have not responded adequately to other antidepressants.
Name
Tranylcypromine
Raw Name
TRANYLCYPROMINE SULFATE
Category
Other
Salt Form
Sulfate
Drug Count
3
Variant Count
5
Last Verified
February 17, 2026
RxCUI
313447, 104838
UNII
7ZAT6ES870
About Tranylcypromine
Tranylcypromine is a potent, non-selective, and irreversible monoamine oxidase inhibitor (MAOI) indicated for the treatment of major depressive disorder (MDD) in adult patients who have not responded adequately to other antidepressants.
Detailed information about Tranylcypromine
This page is for informational purposes only and does not replace medical advice. Consult a qualified healthcare professional before using any medication containing Tranylcypromine.
Tranylcypromine (tranylcypromine sulfate) is a potent, non-selective, and irreversible monoamine oxidase inhibitor (MAOI). It belongs to a specialized class of antidepressant medications that were among the first to be developed for the treatment of psychiatric disorders. Chemically, tranylcypromine is a cyclopropylamine derivative, which distinguishes it from the hydrazine-based MAOIs that preceded it. It is primarily indicated for the treatment of major depressive disorder (MDD) in adult patients who have not responded adequately to other antidepressant therapies, a condition often referred to as treatment-resistant depression (TRD).
The history of tranylcypromine dates back to its development in the late 1950s, receiving FDA approval in 1961 under the brand name Parnate. Unlike many modern antidepressants, such as SSRIs or SNRIs, tranylcypromine works by permanently disabling the enzymes responsible for breaking down key neurotransmitters. Because of its potency and the potential for serious interactions with certain foods and other medications, it is typically reserved as a second- or third-line treatment option. However, for patients with 'atypical' depression—characterized by mood reactivity, oversleeping, and overeating—or for those who have failed multiple other trials, tranylcypromine remains a highly effective clinical tool.
Tranylcypromine exerts its antidepressant effects through the irreversible inhibition of the enzymes monoamine oxidase type A (MAO-A) and type B (MAO-B). These enzymes are located in the outer mitochondrial membranes of neurons and are responsible for the oxidative deamination (breakdown) of monoamine neurotransmitters, including norepinephrine, serotonin, and dopamine.
At the molecular level, tranylcypromine acts as a 'suicide substrate.' It binds covalently to the flavin adenine dinucleotide (FAD) cofactor within the MAO enzyme. Once bound, the enzyme is permanently deactivated. Because the inhibition is irreversible, the clinical effects of tranylcypromine persist until the body can synthesize new MAO enzymes, a process that typically takes 10 to 14 days after the medication is discontinued. By preventing the breakdown of these neurotransmitters, tranylcypromine increases their concentration within the synaptic cleft (the space between neurons), thereby enhancing signal transmission in brain circuits associated with mood regulation. Additionally, tranylcypromine has a minor secondary effect of inhibiting the reuptake of norepinephrine and dopamine, further contributing to its stimulating and mood-elevating properties.
Understanding the pharmacokinetics of tranylcypromine is essential for safe prescribing and monitoring.
Tranylcypromine is FDA-approved for the treatment of Major Depressive Disorder (MDD) in adults who have not responded to other treatments. It is particularly valued in the following clinical scenarios:
Tranylcypromine is primarily available in the following form:
Currently, there are no approved liquid, injectable, or extended-release formulations of tranylcypromine in the United States.
> Important: Only your healthcare provider can determine if Tranylcypromine is right for your specific condition. Because of the dietary and medication restrictions required, a thorough evaluation of a patient's ability to adhere to a low-tyramine diet is necessary before initiation.
The dosing of tranylcypromine must be highly individualized and should be titrated slowly to minimize side effects, particularly orthostatic hypotension (a drop in blood pressure upon standing).
Tranylcypromine is NOT approved for use in pediatric patients (children and adolescents under the age of 18). The safety and efficacy of tranylcypromine in this population have not been established. Furthermore, the risk of suicidality associated with antidepressant use is particularly high in children and young adults, making the use of a potent MAOI like tranylcypromine generally inappropriate for this age group.
Tranylcypromine should be used with extreme caution in patients with significant renal impairment. While the drug is extensively metabolized by the liver, the metabolites are excreted renally. Accumulation of these metabolites in patients with low glomerular filtration rates (GFR) may increase the risk of toxicity. Dosage reduction or increased monitoring is recommended.
Tranylcypromine is contraindicated in patients with a history of liver disease or abnormal liver function tests. Because the liver is the primary site for the metabolism of both the drug and tyramine (via MAO-A in the gut and liver), hepatic impairment significantly increases the risk of a hypertensive crisis and hepatotoxicity.
Geriatric patients (65 years and older) are more susceptible to the side effects of tranylcypromine, particularly orthostatic hypotension and sedation. Healthcare providers typically start elderly patients at a lower dose (e.g., 10 mg per day) and titrate much more slowly. Frequent blood pressure monitoring is essential in this population to prevent falls and related injuries.
If you miss a dose of tranylcypromine, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and resume your regular schedule. Do not double the dose to catch up, as this significantly increases the risk of a sudden spike in blood pressure.
Tranylcypromine overdose is a medical emergency and can be fatal. Symptoms may not appear immediately and can be delayed for several hours after ingestion.
> Important: Follow your healthcare provider's dosing instructions precisely. Do not adjust your dose or stop taking this medication without medical guidance, as sudden discontinuation can lead to withdrawal symptoms.
Most patients taking tranylcypromine will experience at least one side effect, especially during the first few weeks of treatment as the body adjusts to the medication.
> Warning: Stop taking Tranylcypromine and call your doctor or emergency services immediately if you experience any of the following serious symptoms.
With prolonged use, some patients may develop a tolerance to the blood-pressure-lowering effects, but the risk of hypertensive crisis remains constant as long as the drug is in the system. Long-term use has also been associated with weight changes (though less common than with other MAOIs like phenelzine) and potential changes in sleep architecture that may require additional management.
Tranylcypromine carries the FDA-mandated Black Box Warning for suicidality in children, adolescents, and young adults.
Summary of Warning: Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults (ages 18-24) in short-term studies of major depressive disorder and other psychiatric disorders. Anyone considering the use of tranylcypromine in a young person must balance this risk with the clinical need. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Tranylcypromine is not approved for use in pediatric patients.
Report any unusual symptoms or changes in mood to your healthcare provider immediately. Regular monitoring of blood pressure is a standard part of tranylcypromine therapy.
Tranylcypromine is a high-alert medication due to its potential for life-threatening interactions. Patients must be fully educated on the dietary and drug restrictions before starting therapy. It is recommended that patients carry a medical alert card or wear a bracelet stating they are taking an MAOI.
Suicidality and Antidepressant Drugs:
As with all FDA-approved antidepressants, tranylcypromine carries a warning regarding the increased risk of suicidal thinking and behavior in children, adolescents, and young adults (under age 25). While this risk has not been shown to increase in adults over age 24, all patients starting antidepressant therapy should be monitored closely for worsening of depression, emergence of suicidal thoughts, or unusual changes in behavior, such as extreme agitation, irritability, or impulsivity.
Patients taking tranylcypromine require regular clinical follow-up:
Tranylcypromine may cause dizziness, blurred vision, or drowsiness, particularly during the first few weeks of treatment or after a dose increase. You should not drive, operate heavy machinery, or engage in dangerous activities until you know how this medication affects you.
Alcohol must be used with extreme caution, and many types are strictly forbidden. Most beers (especially tap/draft beers and microbrews) and red wines contain significant amounts of tyramine and can trigger a hypertensive crisis. While some distilled spirits and certain bottled beers may be lower in tyramine, the safest course of action is to avoid alcohol entirely while taking an MAOI.
Do not stop taking tranylcypromine abruptly. Sudden discontinuation can lead to a withdrawal syndrome characterized by nausea, vomiting, dizziness, nightmares, and a return of depressive symptoms. If the drug must be stopped, your doctor will provide a tapering schedule. Furthermore, remember that the dietary and drug restrictions must continue for 14 days after the last dose, as the enzyme inhibition persists.
> Important: Discuss all your medical conditions, including any history of heart disease, high blood pressure, or liver problems, with your healthcare provider before starting Tranylcypromine.
The following medications must NEVER be used with tranylcypromine. A washout period of at least 14 days is required when switching from tranylcypromine to these drugs, and often longer (e.g., 5 weeks for fluoxetine) when switching from these drugs to tranylcypromine.
This is the most critical aspect of tranylcypromine therapy. You must avoid 'High-Tyramine' foods:
Tranylcypromine may interfere with certain diagnostic tests, including:
For each major interaction, the mechanism usually involves either the accumulation of neurotransmitters (pharmacodynamic) or the inhibition of metabolism (pharmacokinetic). The clinical consequence is often a hypertensive crisis or Serotonin Syndrome. Management always involves stopping the offending agent and providing emergency supportive care.
> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter cold and allergy medicines.
Tranylcypromine must NEVER be used in patients with the following conditions:
These conditions require a careful risk-benefit analysis by a specialist:
While tranylcypromine is structurally unique, patients who have had a severe allergic reaction (anaphylaxis) to other MAOIs, such as phenelzine or isocarboxazid, should use tranylcypromine with extreme caution, although cross-reactivity is not well-documented.
> Important: Your healthcare provider will evaluate your complete medical history, including any history of heart, liver, or brain-related conditions, before prescribing Tranylcypromine.
Tranylcypromine is classified under FDA Pregnancy Category C. This means that animal reproduction studies have shown an adverse effect on the fetus, and there are no adequate and well-controlled studies in humans.
It is not known whether tranylcypromine is excreted in human milk. However, because many drugs are excreted in milk and because of the potential for serious adverse reactions in nursing infants (such as irritability or blood pressure changes), a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Tranylcypromine is NOT approved for use in children or adolescents. The safety and effectiveness have not been established in this population. The risk of suicidal ideation and the difficulty of maintaining a strict low-tyramine diet in children make this medication generally unsuitable for pediatric psychiatric care.
Clinical studies of tranylcypromine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, clinical experience indicates that the elderly are much more prone to:
In patients with impaired renal function, the clearance of tranylcypromine metabolites may be reduced. While no specific GFR-based dosing tables exist, a 'start low and go slow' approach is mandatory. If the GFR is below 30 mL/min, the drug should be used with extreme caution, if at all.
Tranylcypromine is contraindicated in patients with hepatic impairment. The liver's ability to process tyramine is compromised in these patients, making even small amounts of dietary tyramine potentially lethal. Furthermore, the drug's own metabolism is slowed, leading to toxic accumulation.
> Important: Special populations require individualized medical assessment. Always inform your doctor if you are pregnant, planning to become pregnant, or are breastfeeding.
Tranylcypromine is a non-hydrazine monoamine oxidase inhibitor (MAOI). Its primary mechanism is the irreversible and non-selective inhibition of the enzymes MAO-A and MAO-B.
By inhibiting both, tranylcypromine leads to a rapid and sustained increase in the concentrations of these monoamines in the brain. Unlike some other MAOIs, tranylcypromine also has a structural similarity to amphetamine, allowing it to act as a weak releasing agent of norepinephrine and dopamine, which may explain its faster onset of 'energizing' effects compared to other antidepressants.
| Parameter | Value |
|---|---|
| Bioavailability | High (Rapidly absorbed) |
| Protein Binding | 10% - 20% |
| Half-life | 1.5 - 3 hours (Plasma) |
| Tmax | 1 - 3 hours |
| Metabolism | Hepatic (CYP2A6, CYP2C19) |
| Excretion | Renal (80% as metabolites) |
Tranylcypromine is classified as a Non-selective, Irreversible Monoamine Oxidase Inhibitor (MAOI). It is grouped with other MAOIs like phenelzine (Nardil) and isocarboxazid (Marplan), though it is generally considered more stimulating than its peers.
Medications containing this ingredient
Common questions about Tranylcypromine
Tranylcypromine is primarily used to treat major depressive disorder (MDD) in adults who have not responded well to other antidepressant medications. It is often considered a treatment of last resort for 'treatment-resistant depression' because of its strict dietary and medication requirements. Healthcare providers may also prescribe it for 'atypical' depression, where patients experience mood reactivity and physical heaviness. Because it is highly potent, it is usually only started after other options like SSRIs or SNRIs have failed. It works by increasing the levels of serotonin, norepinephrine, and dopamine in the brain.
The most common side effect is orthostatic hypotension, which is a sudden drop in blood pressure when you stand up, leading to dizziness or lightheadedness. Many patients also experience significant insomnia because the drug has a stimulating effect similar to mild amphetamines. Other frequent side effects include dry mouth, blurred vision, restlessness, and a rapid heart rate. Some people may also notice gastrointestinal issues like nausea or constipation. Most of these side effects are most intense during the first few weeks of treatment and may lessen as your body adjusts.
Alcohol consumption is very restricted and generally discouraged while taking tranylcypromine. Many alcoholic beverages, especially draft beers, microbrews, and certain red wines (like Chianti), contain high levels of tyramine, which can trigger a life-threatening hypertensive crisis. While some domestic bottled beers or clear liquors may be lower in tyramine, the risk of a severe reaction is high enough that most doctors recommend total abstinence. Additionally, alcohol can worsen the dizziness and sedation caused by the medication. Always consult your doctor before consuming any form of alcohol while on an MAOI.
Tranylcypromine is generally not recommended during pregnancy unless the benefits clearly outweigh the potential risks to the fetus. It is classified as FDA Category C, meaning there is evidence of harm in animal studies but insufficient data in humans. One major concern is that the drug can affect blood flow to the placenta, potentially impacting the baby's growth. There is also the risk of a hypertensive crisis in the mother, which is a medical emergency for both. If you are planning to become pregnant, you should discuss alternative antidepressant options with your healthcare provider well in advance.
While tranylcypromine begins to inhibit brain enzymes within a few hours of the first dose, the actual relief from depressive symptoms usually takes longer. Most patients begin to feel an improvement in energy and mood within 2 to 4 weeks of consistent use. In some cases, it may take up to 6 to 8 weeks to see the full clinical benefit, especially as the dose is being titrated upward. It is important to continue taking the medication exactly as prescribed, even if you do not feel better immediately. If there is no improvement after 6 weeks at a therapeutic dose, your doctor may reevaluate the treatment plan.
No, you should never stop taking tranylcypromine abruptly. Doing so can lead to a withdrawal syndrome that includes symptoms like nausea, vomiting, sweating, dizziness, and a rapid return of severe depression or anxiety. In rare cases, sudden discontinuation has been linked to more serious neurological symptoms. Your doctor will provide a gradual tapering schedule to slowly lower the dose over several weeks. Furthermore, you must continue to follow the low-tyramine diet for at least 14 days after your very last dose, as the drug's effects on your enzymes persist for about two weeks.
If you miss a dose, take it as soon as you remember that day. However, if it is almost time for your next scheduled dose, you should skip the missed dose and simply take the next one at the regular time. Never take two doses at once to make up for a missed one, as this can cause a dangerous spike in your blood pressure. If you miss multiple doses in a row, contact your healthcare provider for instructions on how to restart. Keeping a daily pill organizer can be a helpful way to ensure you stay on track with your medication schedule.
Tranylcypromine is generally considered 'weight neutral' compared to other older antidepressants like phenelzine or tricyclic antidepressants. While some patients may experience a slight increase in appetite as their depression improves, it does not typically cause the significant metabolic changes associated with massive weight gain. In fact, because it is somewhat stimulating, some patients may actually experience a slight decrease in appetite or weight loss. However, everyone reacts differently to psychiatric medications. If you notice significant changes in your weight, you should discuss them with your doctor to determine the cause and manage it appropriately.
Tranylcypromine has a very long list of dangerous drug interactions, making it one of the most complex medications to manage. It cannot be taken with most other antidepressants, including SSRIs like Lexapro or SNRIs like Cymbalta, due to the risk of Serotonin Syndrome. It also interacts dangerously with common over-the-counter medicines like decongestants (pseudoephedrine) and certain cough syrups (dextromethorphan), which can cause fatal blood pressure spikes. Even certain pain medications like meperidine are strictly forbidden. You must provide your doctor and pharmacist with a complete list of every medication, supplement, and herbal product you use before starting tranylcypromine.
Yes, tranylcypromine is available as a generic medication in the United States, which typically makes it more affordable than the brand-name version, Parnate. The generic version contains the same active ingredient (tranylcypromine sulfate) and is held to the same FDA standards for safety and effectiveness as the brand-name drug. Both the generic and brand versions are usually only available in a 10 mg tablet strength. While the appearance of the tablets may differ between manufacturers, the clinical effect remains the same. Most insurance plans cover the generic version of this medication.