Tranylcypromine

Antidepressant, irreversible non-selective monoamine oxidase inhibitor (MAO-A and MAO-B), amphetamine derivative

ATC code: N06AF04

Brand names: Parnate

Updated 4 Jun 2026 · Methodology

Indications

Treatment-resistant depression

Third line

Tranylcypromine is a third-line antidepressant for treatment-resistant depression. In Spain it is preferred over phenelzine in apathetic or anergic presentations because the amphetamine-like effect adds activation. SEPB restricts prescribing to inpatient or specialist outpatient settings after SSRI/SNRI washout. A tyramine-free diet and blood pressure checks every 2 weeks for the first 2 months are mandatory.

Sources

AEMPS: Ficha tecnica de Parnate (tranilcipromina) (2023)

ICD-10: F33 · ICD-11: 6A72

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Irreversibly inhibits MAO-A and MAO-B, raising synaptic serotonin, noradrenaline and dopamine. Unlike phenelzine, tranylcypromine has an amphetamine-like backbone that adds catecholamine-releasing activity. Onset is faster (1–3 weeks), but the risk of tyramine-induced hypertensive crisis is higher.

Safety

Contraindications

Any serotonergic drug (SSRI, SNRI, TCA, clomipramine, mirtazapine, triptans, tramadol, pethidine, dextromethorphan, methadone, linezolid)
Sympathomimetics (pseudoephedrine, ephedrine, phenylephrine), levodopa, dopamine agonists
Phaeochromocytoma, thyrotoxicosis
Severe hepatic impairment, cerebrovascular disease
Prior tyramine-induced hypertensive crisis

Serious adverse effects

Tyramine-induced hypertensive crisis
Serotonin syndrome
Hepatotoxicity

Common adverse effects

Orthostatic hypotension
Insomnia
Anxiety
Tachycardia
Decreased libido
Dizziness

Pregnancy: can you take Tranylcypromine?

Pregnancy data are limited. Switch to an antidepressant with a better profile when planning pregnancy.

Breastfeeding: can you take Tranylcypromine?

Breastfeeding during treatment is not recommended.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Drug–drug interactions

9 pairs found. Sorted from critical to minor.

CriticalAlmotriptanSelective serotonin 5HT1B/1D agonists (triptans)

Mechanism

MAO-A inhibition + triptan – fatal serotonin syndrome.

Symptoms

Agitation, tachycardia, hyperthermia, myoclonus, hyperreflexia within hours.

Management

Combination contraindicated. 14 days after MAOI withdrawal before starting triptan.

Sources

Pair details →Almotriptan →

CriticalDextromethorphanCentrally acting cough suppressant

Mechanism

Tranylcypromine is an irreversible, non-selective monoamine oxidase (MAO) inhibitor; MAO is the enzyme that breaks down serotonin, noradrenaline and dopamine (tranylcypromine SmPC, section 5.1). Dextromethorphan has serotonergic effects, and together with MAO inhibitors it can cause life-threatening serotonin syndrome (dextromethorphan SmPC, section 4.4). Part of the reaction may come from slower breakdown of dextromethorphan in the liver (dextromethorphan SmPC, section 4.5). Because MAO inhibition is irreversible, enzyme activity takes 3–5 days to return after the last dose of tranylcypromine (tranylcypromine SmPC, section 5.1). Inhibition may persist for up to 10 days (US Food and Drug Administration () tranylcypromine label).

Symptoms

Monoamine oxidase inhibitors combined with dextromethorphan have caused serotonin syndrome with agitation, sweating, rigidity and hypertension (dextromethorphan SmPC, section 4.5). The combination has also caused nausea, coma, hypotension, leg tremor, muscle spasms and hyperpyrexia that can lead to myocardial infarction and death (dextromethorphan orodispersible tablets SmPC, section 4.5). Serotonin syndrome may include changes in mental state, autonomic instability, neuromuscular abnormalities and gastrointestinal symptoms (dextromethorphan SmPC, section 4.4). Tranylcypromine and dextromethorphan together can have life-threatening effects on the central nervous system, breathing and circulation (tranylcypromine SmPC, section 4.5). Psychosis and bizarre behaviour are also possible (US Food and Drug Administration () tranylcypromine label).

Management

The combination is contraindicated (dextromethorphan SmPC, sections 4.3 and 4.5, which name tranylcypromine; tranylcypromine SmPC, sections 4.3 and 4.5; US Food and Drug Administration () tranylcypromine label, section 4.1). Avoid dextromethorphan for 14 days after stopping tranylcypromine (dextromethorphan SmPC, sections 4.3 and 4.5; tranylcypromine SmPC, section 4.2; FDA over-the-counter dextromethorphan label). Start tranylcypromine no earlier than 4–5 half-lives of dextromethorphan and its active metabolite after the last dose of dextromethorphan (FDA tranylcypromine label, section 7.1). Dextromethorphan is an ingredient of cough medicines (tranylcypromine SmPC, section 4.3). A patient taking tranylcypromine should therefore not use over-the-counter medicines or supplements without first asking a doctor or pharmacist (FDA tranylcypromine label, section 7.1). Nasal, cough and cold products may also contain indirect sympathomimetics, which are contraindicated with tranylcypromine because of the risk of severe hypertensive crisis (tranylcypromine SmPC, sections 4.3 and 4.5). If serotonin syndrome is suspected, stop dextromethorphan (dextromethorphan SmPC, section 4.4), stop tranylcypromine and other serotonergic drugs at once and start supportive symptomatic treatment (FDA tranylcypromine label, section 5.3).

Sources

Pair details →Dextromethorphan →

CriticalFluoxetineSelective serotonin reuptake inhibitors

Mechanism

Tranylcypromine is an irreversible MAOI. Combined with fluoxetine causes serotonin syndrome. AEMPS Parnate Section 4.3.

Symptoms

Hyperthermia, myoclonus, tachycardia, hypertension.

Management

Combination contraindicated. 5-week washout from fluoxetine.

Sources

Pair details →Fluoxetine →

CriticalLinezolidOxazolidinone antibiotic

Mechanism

Cumulative MAO inhibition (irreversible tranylcypromine + reversible linezolid). Severe serotonin syndrome with tyramine load.

Symptoms

Hypertensive crisis, hyperthermia.

Management

Combination contraindicated.

Sources

AEMPS: Ficha tecnica de Parnate (tranilcipromina) (2023)

Pair details →Linezolid →

CriticalMeperidineOpioid analgesic, phenylpiperidine class

Mechanism

Same pharmacodynamics – fatal serotonin syndrome.

Symptoms

Hyperthermia, myoclonus, coma.

Management

Combination contraindicated.

Sources

Pair details →Meperidine →

CriticalRizatriptanSelective 5-HT1B/1D serotonin receptor agonist

Mechanism

MAO-A inhibition by tranylcypromine + rizatriptan – fatal serotonin syndrome.

Symptoms

Agitation, tachycardia, hyperthermia, myoclonus, hyperreflexia within hours.

Management

Combination contraindicated. 14 days after MAOI withdrawal before starting triptan.

Sources

Pair details →Rizatriptan →

CriticalSumatriptanSelective 5-HT1B/1D serotonin receptor agonist

Mechanism

Tranylcypromine irreversibly inhibits MAO-A. Sumatriptan accumulates – fatal serotonin syndrome.

Symptoms

Agitation, tachycardia, hyperthermia, myoclonus, hyperreflexia within hours.

Management

Combination contraindicated. 14 days after MAOI withdrawal before starting triptan.

Sources

Pair details →Sumatriptan →

CriticalTramadolOther opioids

Mechanism

Tranylcypromine irreversibly inhibits MAO. Tramadol inhibits serotonin reuptake. Combination causes fatal serotonin syndrome.

Symptoms

Hyperthermia, myoclonus, agitation, seizures.

Management

Combination contraindicated. Alternative analgesic: paracetamol.

Sources

Pair details →Tramadol →

CriticalZolmitriptanTriptan, selective 5HT1B/1D receptor agonist

Mechanism

MAO-A inhibition + zolmitriptan – fatal serotonin syndrome.

Symptoms

Agitation, tachycardia, hyperthermia, myoclonus, hyperreflexia within hours.

Management

Combination contraindicated. 14 days after MAOI withdrawal before starting triptan.

Sources

Pair details →Zolmitriptan →

Label mentions69 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

CriticalBupropion
«Combination with Certain Drugs: Antidepressants including but not limited to: Other monoamine oxidase inhibitors (MAOIs) Selective serotonin reuptake inhibitors (SSRIs) and serotonin and…»
FDA, section 4 · Open on DailyMed
CriticalCarbamazepine
«Combination with Certain Drugs: carbamazepine meperidine tapentadol»
FDA, section 4 · Open on DailyMed
CriticalCitalopram
«Síndrome serotoninérgico: Los casos sospechosos de interacciones de antidepresivos prescritos con frecuencia (por ejemplo, citalopram, paroxetina, venlafaxina, duloxetina, amitriptilina) con…»
AEMPS, section 4.4 · Open on CIMA
CriticalDextromethorphan
«petidina, tramadol, dextrometorfano (dextrometorfano contenido en antitusivos);»
AEMPS, section 4.3 · Open on CIMA
CriticalDextromethorphan
«Combination with Certain Drugs: dextromethorphan milnacipran tryptophan»
FDA, section 4 · Open on DailyMed
CriticalDisulfiram
«disulfiram;»
AEMPS, section 4.3 · Open on CIMA
CriticalDuloxetine
«medicamentos con una marcada inhibición de la recaptación de serotonina, como todos los inhibidores selectivos de la recaptación de serotonina, clomipramina, venlafaxina, duloxetina, milnaciprán…»
AEMPS, section 4.3 · Open on CIMA
CriticalFluoxetine
«Clinically-Significant Drug Interactions: For products that are contraindicated with tranylcypromine tablets, a time period of 4 to 5 half-lives of the other product or any active metabolite should…»
FDA, section 7 · Open on DailyMed
CriticalISRSclass named in the label
«medicamentos con una marcada inhibición de la recaptación de serotonina, como todos los inhibidores selectivos de la recaptación de serotonina, clomipramina, venlafaxina, duloxetina, milnaciprán…»
AEMPS, section 4.3 · Open on CIMA
CriticalL-tryptophan
«L-triptófano;»
AEMPS, section 4.3 · Open on CIMA
CriticalLinezolid
«Clinically-Significant Drug Interactions: If in the absence of therapeutic alternatives and emergency treatment with a contraindicated drug (e.g., linezolid, intravenous methylene blue, direct-acting…»
FDA, section 7 · Open on DailyMed
Criticalmedicamentos serotoninérgicosclass named in the label
«Síndrome serotoninérgico: Los casos sospechosos de interacciones de antidepresivos prescritos con frecuencia (por ejemplo, citalopram, paroxetina, venlafaxina, duloxetina, amitriptilina) con…»
AEMPS, section 4.4 · Open on CIMA
CriticalMeperidine
«petidina, tramadol, dextrometorfano (dextrometorfano contenido en antitusivos);»
AEMPS, section 4.3 · Open on CIMA
CriticalMeperidine
«Combination with Certain Drugs: carbamazepine meperidine tapentadol»
FDA, section 4 · Open on DailyMed
CriticalMethyldopa
«Combination with Certain Drugs: cyclobenzaprine methyldopa tetrabenazine»
FDA, section 4 · Open on DailyMed
CriticalMethylphenidate
«Combination with Certain Drugs: Amphetamines and methylphenidates and derivatives»
FDA, section 4 · Open on DailyMed
CriticalMirtazapine
«Clinically-Significant Drug Interactions: Mirtazapine Contraindicated SS»
FDA, section 7 · Open on DailyMed
CriticalParoxetine
«Síndrome serotoninérgico: Los casos sospechosos de interacciones de antidepresivos prescritos con frecuencia (por ejemplo, citalopram, paroxetina, venlafaxina, duloxetina, amitriptilina) con…»
AEMPS, section 4.4 · Open on CIMA
CriticalPseudoephedrine
«Combination with Certain Drugs: Sympathomimetic products (e.g., cold, hay fever or weight-reducing products that contain vasoconstrictors such as pseudoephedrine, phenylephrine, and ephedrine; or…»
FDA, section 4 · Open on DailyMed
CriticalRasagiline
«Combination with Certain Drugs: dopamine rasagiline»
FDA, section 4 · Open on DailyMed
CriticalSSRIs/SNRIsclass named in the label
«CONTRAINDICATIONS: Concomitant use or use in rapid succession with other MAOIs; selective serotonin reuptake inhibitors; serotonin and norepinephrine reuptake inhibitors; tricyclic antidepressants…»
FDA, section 4 · Open on DailyMed
Criticalsympathomimeticsclass named in the label
«CONTRAINDICATIONS: Concomitant use or use in rapid succession with other MAOIs; selective serotonin reuptake inhibitors; serotonin and norepinephrine reuptake inhibitors; tricyclic antidepressants…»
FDA, section 4 · Open on DailyMed
CriticalTapentadol
«Combination with Certain Drugs: carbamazepine meperidine tapentadol»
FDA, section 4 · Open on DailyMed
CriticalTramadol
«petidina, tramadol, dextrometorfano (dextrometorfano contenido en antitusivos);»
AEMPS, section 4.3 · Open on CIMA
CriticalTrazodone
«Combination with Certain Drugs: Antidepressants including but not limited to: Other monoamine oxidase inhibitors (MAOIs) Selective serotonin reuptake inhibitors (SSRIs) and serotonin and…»
FDA, section 4 · Open on DailyMed
Criticaltricyclic antidepressantsclass named in the label
«CONTRAINDICATIONS: Concomitant use or use in rapid succession with other MAOIs; selective serotonin reuptake inhibitors; serotonin and norepinephrine reuptake inhibitors; tricyclic antidepressants…»
FDA, section 4 · Open on DailyMed
Criticaltriptanesclass named in the label
«antagonistas de la serotonina como los triptanes para el tratamiento de la migraña;»
AEMPS, section 4.3 · Open on CIMA
Criticaltriptansclass named in the label
«Combination with Certain Drugs: Triptans»
FDA, section 4 · Open on DailyMed
CriticalVenlafaxine
«medicamentos con una marcada inhibición de la recaptación de serotonina, como todos los inhibidores selectivos de la recaptación de serotonina, clomipramina, venlafaxina, duloxetina, milnaciprán…»
AEMPS, section 4.3 · Open on CIMA
CriticalVortioxetine
«medicamentos con una marcada inhibición de la recaptación de serotonina, como todos los inhibidores selectivos de la recaptación de serotonina, clomipramina, venlafaxina, duloxetina, milnaciprán…»
AEMPS, section 4.3 · Open on CIMA
CriticalVortioxetine
«Combination with Certain Drugs: Antidepressants including but not limited to: Other monoamine oxidase inhibitors (MAOIs) Selective serotonin reuptake inhibitors (SSRIs) and serotonin and…»
FDA, section 4 · Open on DailyMed
MajorAmitriptyline
«En casos individuales de depresión refractaria, la administración adicional de tranilcipromina con el tratamiento antidepresivo tricíclico existente (pero no con clomipramina, imipramina y…»
AEMPS, section 4.4 · Open on CIMA
Majorantidepresivos tricíclicosclass named in the label
«En casos individuales de depresión refractaria, la administración adicional de tranilcipromina con el tratamiento antidepresivo tricíclico existente (pero no con clomipramina, imipramina y…»
AEMPS, section 4.4 · Open on CIMA
MajorBupropion
«Influencia en el efecto de otros medicamentos: Los efectos adversos de bupropión (o anfebutamona – agente para la deshabituación tabáquica), como las convulsiones y los estados de excitación, pueden…»
AEMPS, section 4.5 · Open on CIMA
MajorPseudoephedrine
«Influencia en el efecto de tranilcipromina: Se debe evitar la combinación con simpaticomiméticos directos como la dopamina o la pseudoefedrina (por ejemplo, en fármacos cardiovasculares para el…»
AEMPS, section 4.5 · Open on CIMA
Majorsimpaticomiméticosclass named in the label
«simpaticomiméticos indirectos (contenidos, por ejemplo, en agentes que aumentan la presión sanguínea y en ciertos remedios nasales, antitusígenos o antigripales);»
AEMPS, section 4.3 · Open on CIMA
Moderateantidiabéticosclass named in the label
«Influencia en el efecto de otros medicamentos: Puede potenciarse el efecto de insulina y de antidiabéticos orales. Puede ser necesario un ajuste de dosis (ver también sección 4.4).»
AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

CriticalDextromethorphan
«- Antidepresivos inhibidores de la monoaminoxidasa (IMAO) como moclobemida y tranilcipromina; antidepresivos inhibidores de la recaptación de la serotonina (ISRS) como fluoxetina y paroxetina…»
AEMPS, section 4.5 · Open on CIMA
CriticalPhenelzine
«CONTRAINDICATIONS: pargyline hydrochloride pargyline hydrochloride and methylclothiazide furazolidone isocarboxazid procarbazine tranylcypromine»
FDA, section 4 · Open on DailyMed
CriticalPseudoephedrine
«Inhibidores de la monoaminooxidasa (IMAO): se debe evitar la administración conjunta de este medicamento e incluso en los 15 días posteriores a la finalización del tratamiento con IMAO…»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Tranylcypromine used for?

Tranylcypromine is evaluated for the following indications with varying evidence strength: Treatment-resistant depression (evidence tier B). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Tranylcypromine?

Common side effects of Tranylcypromine (≥ 1 in 100): Orthostatic hypotension, Insomnia, Anxiety, Tachycardia, Decreased libido, Dizziness. See the Safety section for uncommon and serious reactions.

Is Tranylcypromine safe during pregnancy?

Pregnancy data are limited. Switch to an antidepressant with a better profile when planning pregnancy.

Is Tranylcypromine compatible with breastfeeding?

Breastfeeding during treatment is not recommended.

Who should not take Tranylcypromine?

Tranylcypromine is contraindicated in: Any serotonergic drug (SSRI, SNRI, TCA, clomipramine, mirtazapine, triptans, tramadol, pethidine, dextromethorphan, methadone, linezolid); Sympathomimetics (pseudoephedrine, ephedrine, phenylephrine), levodopa, dopamine agonists; Phaeochromocytoma, thyrotoxicosis; Severe hepatic impairment, cerebrovascular disease; Prior tyramine-induced hypertensive crisis. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 08/19/2026
FDA / DailyMedLabel dated 07/22/2026

Other drugs in this group

Trazodone, Venlafaxine, Vinpocetine, Vortioxetine, Atomoxetine, Escitalopram, Hypericum perforatum, Phenylpiracetam (fonturacetam)