Tranylcypromine

FDA prescribing information

DailyMed, U.S. National Library of Medicine. PARNATE (tranylcypromine sulfate) film-coated oral tablets, prescribing information, label version effective 2 July 2025. Set ID b72d8187-dfcc-4ea0-b5e9-c0be95b69a27.

PARNATE is labeled for major depressive disorder in adults who have not responded adequately to other antidepressants; the label says it is not indicated for initial treatment because of the potential for serious adverse reactions and drug interactions and the need for dietary restrictions. A boxed warning covers suicidal thoughts and behaviors in children and young adults and hypertensive crisis with significant tyramine intake or certain drugs, during use or after stopping. The label names the active ingredient (+/-)-trans-2-phenylcyclopropylamine sulfate (2:1), a racemate, and expresses doses as tranylcypromine. It is not approved for pediatric use. The label contraindicates use with, or in rapid succession with, other MAOIs; SSRIs, SNRIs, tricyclics, and other antidepressants including bupropion and trazodone; amphetamines, methylphenidates, and derivatives; sympathomimetic products, including cold, hay fever, or weight-reducing products with pseudoephedrine, phenylephrine, or ephedrine and dietary supplements containing sympathomimetics; triptans; and individual drugs including buspirone, meperidine, tapentadol, dextromethorphan, tryptophan, SAM-e, levodopa, carbamazepine, cyclobenzaprine, and milnacipran. Pheochromocytoma is also a contraindication. High-tyramine foods and drinks are to be avoided during treatment and after stopping, including aged cheeses, air-dried, aged, or fermented meats and salamis, pickled herring, spoiled meat, fava bean pods, tap and unpasteurized beer, concentrated yeast extract, sauerkraut, most soybean products, tyramine supplements, and chocolate; excessive caffeine is also listed, and alcohol is not recommended. A hypertensive emergency is described as, for example, blood pressure above 180/120 mm Hg with organ dysfunction, intracranial bleeding (sometimes fatal) has been reported, and blood pressure rises have also occurred without tyramine. Serotonin syndrome can occur with serotonergic drugs. Tranylcypromine is eliminated within 24 hours, but MAO activity takes up to 3 to 5 days to recover and inhibition may persist up to 10 days, and a washout period is required before starting another MAOI or a contraindicated antidepressant. The label reports abuse of PARNATE, in some cases in people with prior substance abuse, and dependence shown by withdrawal effects after abrupt discontinuation: delirium (even with low daily doses), restlessness, anxiety, confusion, hallucinations, headache, weakness, diarrhea, or rapid relapse into depression, plus thrombocytopenia and liver enzyme increases after withdrawal from high doses. Withdrawal effects appeared within 1 to 3 days and persisted for several weeks, and higher-than-recommended doses and longer use carried higher risk.

Participants / model

Adults with major depressive disorder not adequately responsive to other antidepressants; adults prescribed PARNATE, including postmarketing reports

Treatment

PARNATE film-coated oral tablets

Follow-up

Label version effective 2 July 2025

Study design

FDA prescribing information

Funding

not stated in the source

The label has no pharmacokinetics section beyond elimination within 24 hours and MAO recovery timing. Dosing, titration and washout day-counts are left out of this page.

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 012342 (PARNATE), with ANDA 040640. Dates read from the openFDA Drugs@FDA records.

FDA approved PARNATE under NDA 012342 on 21 February 1961; the application is now held by Advanz Pharma. A generic tranylcypromine sulfate tablet was approved under ANDA 040640 on 29 June 2006.

Participants / model

Not a clinical population

Treatment

Drug applications

Follow-up

Approvals in 1961 and 2006

Study design

FDA application records

Funding

not stated in the source

These records give approval dates and the current application holder. Indications come from the product label.

Chemical identity record

National Library of Medicine. PubChem compound records CID 5530 (tranylcypromine) and CID 11473982 (tranylcypromine sulfate).

Tranylcypromine: PubChem CID 5530, C9H11N, 133.19 g/mol, named 2-phenylcyclopropan-1-amine without stereochemistry and listing several CAS-format synonyms (155-09-9, 54-97-7, 95-62-5). Tranylcypromine sulfate: CID 11473982, C18H24N2O4S, 364.5 g/mol, CAS 13492-01-8, but PubChem's computed name specifies the (1S,2R) form while the PARNATE label describes a racemate. Label doses are expressed as tranylcypromine.

Participants / model

Chemical identity, not a clinical population

Treatment

Base and sulfate salt

Follow-up

Not applicable

Study design

NLM chemical record

Funding

not stated in the source

PubChem's sulfate stereochemistry conflicts with the racemic label. Supplier products have not been compared with either record, so whether they are the racemate or a single enantiomer is unknown.

Systematic review and meta-analysis

Ricken R et al. Eur Neuropsychopharmacol. 2017;27(8):714-731. PMID 28579071.

Tranylcypromine was superior to placebo (pooled log odds ratio 0.509, 95% CI 0.026 to 0.993, 4 studies) and equal to other antidepressants (0.208, 95% CI -0.128 to 0.544, 10 studies). In depression resistant to tricyclics and SSRIs it was superior to placebo in one study (2.826, 95% CI 1.494 to 4.158) and to non-established antidepressants (1.976, 95% CI 0.907 to 3.045, 4 studies), and equal to other MAOIs and an antidepressant combination (-0.366, 95% CI -0.869 to 0.137, 4 studies). The authors cite controlled studies suggesting a particular advantage in atypical depression and note its third-line place in guidelines because of the tyramine-restricted diet.

Participants / model

Adults with depression, including treatment-resistant depression, in controlled trials

Treatment

Oral tranylcypromine

Follow-up

not stated in the source

Study design

Review with meta-analysis of controlled trials

Funding

not stated in the source

The atypical-depression advantage is cited by the authors from other controlled studies, not measured in this analysis.

Randomized controlled trial

McGrath PJ et al. Am J Psychiatry. 2006;163(9):1531-41; quiz 1666. PMID 16946177.

Remission rates were 6.9% on tranylcypromine (58 patients) and 13.7% on extended-release venlafaxine plus mirtazapine (51 patients), not significantly different. The mean exit dose of tranylcypromine was 36.9 mg, and tranylcypromine produced less symptom reduction and more attrition from intolerance.

Participants / model

109 adult outpatients with nonpsychotic major depression after three failed medication trials

Treatment

Oral tranylcypromine versus extended-release venlafaxine plus mirtazapine

Follow-up

not stated in the source

Study design

Open-label randomized trial; remission defined as HAM-D 7 or less

Funding

not stated in the source

Open-label, in people whose depression had not remitted after three prior medication trials.

Systematic review and meta-analysis

Ricken R et al. Eur Neuropsychopharmacol. 2017;27(8):714-731. PMID 28579071.

Tranylcypromine was superior to placebo (pooled log odds ratio 0.509, 95% CI 0.026 to 0.993, 4 studies) and equal to other antidepressants (0.208, 95% CI -0.128 to 0.544, 10 studies). In depression resistant to tricyclics and SSRIs it was superior to placebo in one study (2.826, 95% CI 1.494 to 4.158) and to non-established antidepressants (1.976, 95% CI 0.907 to 3.045, 4 studies), and equal to other MAOIs and an antidepressant combination (-0.366, 95% CI -0.869 to 0.137, 4 studies). The authors cite controlled studies suggesting a particular advantage in atypical depression and note its third-line place in guidelines because of the tyramine-restricted diet.

Participants / model

Adults with depression, including treatment-resistant depression, in controlled trials

Treatment

Oral tranylcypromine

Follow-up

not stated in the source

Study design

Review with meta-analysis of controlled trials

Funding

not stated in the source

The atypical-depression advantage is cited by the authors from other controlled studies, not measured in this analysis.

Randomized controlled trial

Himmelhoch JM et al. Am J Psychiatry. 1991;148(7):910-6. PMID 2053632.

Tranylcypromine produced lower attrition, greater symptom improvement, and higher global response than imipramine, without more treatment-emergent hypomania or mania. The authors link the advantage to anergia and reversed neurovegetative symptoms such as hypersomnia and hyperphagia.

Participants / model

56 outpatients with anergic bipolar I or II depression (28 per arm)

Treatment

Oral tranylcypromine versus imipramine

Follow-up

not stated in the source

Study design

Double-blind controlled trial

Funding

not stated in the source

The closest trial in these records to atypical or anergic presentations. It enrolled bipolar depression, not unipolar atypical depression.

PubMed search record

PubMed search run on 9 October 2026: tranylcypromine[tiab] AND (healthy OR volunteers OR volunteer)[tiab], 33 records returned; a second search for tranylcypromine with nootropic, cognitive enhancement, cognitive enhancer, smart drug, or neuroenhancement returned 9 records.

The healthy-volunteer search returned 33 records. They covered tyramine pressor testing, pharmacokinetics and assays, MAO inhibition, food and drug interactions, hormone levels, reviews, and unrelated laboratory work; none measured cognition, motivation, drive, or executive function. A second search for tranylcypromine with nootropic, cognitive enhancement, cognitive enhancer, smart drug, or neuroenhancement returned 9 records, all animal, in vitro, or assay work. No human study of tranylcypromine for cognitive or motivational enhancement in healthy people was found.

Participants / model

Records returned, not a population

Treatment

Not applicable

Follow-up

Searches run on 9 October 2026

Study design

Literature search

Funding

not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

FDA prescribing information

DailyMed, U.S. National Library of Medicine. PARNATE (tranylcypromine sulfate) film-coated oral tablets, prescribing information, label version effective 2 July 2025. Set ID b72d8187-dfcc-4ea0-b5e9-c0be95b69a27.

PARNATE is labeled for major depressive disorder in adults who have not responded adequately to other antidepressants; the label says it is not indicated for initial treatment because of the potential for serious adverse reactions and drug interactions and the need for dietary restrictions. A boxed warning covers suicidal thoughts and behaviors in children and young adults and hypertensive crisis with significant tyramine intake or certain drugs, during use or after stopping. The label names the active ingredient (+/-)-trans-2-phenylcyclopropylamine sulfate (2:1), a racemate, and expresses doses as tranylcypromine. It is not approved for pediatric use. The label contraindicates use with, or in rapid succession with, other MAOIs; SSRIs, SNRIs, tricyclics, and other antidepressants including bupropion and trazodone; amphetamines, methylphenidates, and derivatives; sympathomimetic products, including cold, hay fever, or weight-reducing products with pseudoephedrine, phenylephrine, or ephedrine and dietary supplements containing sympathomimetics; triptans; and individual drugs including buspirone, meperidine, tapentadol, dextromethorphan, tryptophan, SAM-e, levodopa, carbamazepine, cyclobenzaprine, and milnacipran. Pheochromocytoma is also a contraindication. High-tyramine foods and drinks are to be avoided during treatment and after stopping, including aged cheeses, air-dried, aged, or fermented meats and salamis, pickled herring, spoiled meat, fava bean pods, tap and unpasteurized beer, concentrated yeast extract, sauerkraut, most soybean products, tyramine supplements, and chocolate; excessive caffeine is also listed, and alcohol is not recommended. A hypertensive emergency is described as, for example, blood pressure above 180/120 mm Hg with organ dysfunction, intracranial bleeding (sometimes fatal) has been reported, and blood pressure rises have also occurred without tyramine. Serotonin syndrome can occur with serotonergic drugs. Tranylcypromine is eliminated within 24 hours, but MAO activity takes up to 3 to 5 days to recover and inhibition may persist up to 10 days, and a washout period is required before starting another MAOI or a contraindicated antidepressant. The label reports abuse of PARNATE, in some cases in people with prior substance abuse, and dependence shown by withdrawal effects after abrupt discontinuation: delirium (even with low daily doses), restlessness, anxiety, confusion, hallucinations, headache, weakness, diarrhea, or rapid relapse into depression, plus thrombocytopenia and liver enzyme increases after withdrawal from high doses. Withdrawal effects appeared within 1 to 3 days and persisted for several weeks, and higher-than-recommended doses and longer use carried higher risk.

Participants / model

Adults with major depressive disorder not adequately responsive to other antidepressants; adults prescribed PARNATE, including postmarketing reports

Treatment

PARNATE film-coated oral tablets

Follow-up

Label version effective 2 July 2025

Study design

FDA prescribing information

Funding

not stated in the source

The label has no pharmacokinetics section beyond elimination within 24 hours and MAO recovery timing. Dosing, titration and washout day-counts are left out of this page.

Randomized controlled trial

Berlin I et al. Clin Pharmacol Ther. 1989;46(3):344-51. PMID 2673623.

Tyramine taken with a meal raised systolic pressure by 30 mm Hg at a mean of 1,200 mg (range 1,000 to 1,600) during placebo but at 35 mg (range 20 to 50) during tranylcypromine 10 mg twice daily, a factor of 38.2; moclobemide gave a factor of 5.0. The pressure rise lasted 126 minutes on tranylcypromine versus 69 on moclobemide.

Participants / model

16 healthy volunteers

Treatment

Oral tranylcypromine 10 mg twice daily; oral tyramine with meals

Follow-up

not stated in the source

Study design

Double-blind placebo-controlled parallel-group study

Funding

not stated in the source

A small healthy-volunteer study from 1988 or 1989. Thresholds in other people can differ.

Human study

Bieck PR et al. J Clin Psychopharmacol. 1988;8(4):237-45. PMID 3209716.

Unmedicated healthy volunteers needed 200 to 800 mg of tyramine to raise systolic pressure by 30 mm Hg. In 12 subjects on tranylcypromine for 8 to 16 days, tyramine sensitivity rose an estimated 56-fold, and full normalization of the pressor response took 30 days after the last dose. Systolic rises above 60 mm Hg occurred in 13% of all 296 tests in the program.

Participants / model

49 healthy volunteers, 12 of whom took tranylcypromine

Treatment

Oral tranylcypromine for 8 to 16 days; oral tyramine challenge

Follow-up

8 to 16 days of tranylcypromine; recovery followed for 30 days

Study design

Clinical pharmacology study with oral tyramine challenges

Funding

not stated in the source

A small healthy-volunteer study from 1988 or 1989.

FDA prescribing information

DailyMed, U.S. National Library of Medicine. PARNATE (tranylcypromine sulfate) film-coated oral tablets, prescribing information, label version effective 2 July 2025. Set ID b72d8187-dfcc-4ea0-b5e9-c0be95b69a27.

PARNATE is labeled for major depressive disorder in adults who have not responded adequately to other antidepressants; the label says it is not indicated for initial treatment because of the potential for serious adverse reactions and drug interactions and the need for dietary restrictions. A boxed warning covers suicidal thoughts and behaviors in children and young adults and hypertensive crisis with significant tyramine intake or certain drugs, during use or after stopping. The label names the active ingredient (+/-)-trans-2-phenylcyclopropylamine sulfate (2:1), a racemate, and expresses doses as tranylcypromine. It is not approved for pediatric use. The label contraindicates use with, or in rapid succession with, other MAOIs; SSRIs, SNRIs, tricyclics, and other antidepressants including bupropion and trazodone; amphetamines, methylphenidates, and derivatives; sympathomimetic products, including cold, hay fever, or weight-reducing products with pseudoephedrine, phenylephrine, or ephedrine and dietary supplements containing sympathomimetics; triptans; and individual drugs including buspirone, meperidine, tapentadol, dextromethorphan, tryptophan, SAM-e, levodopa, carbamazepine, cyclobenzaprine, and milnacipran. Pheochromocytoma is also a contraindication. High-tyramine foods and drinks are to be avoided during treatment and after stopping, including aged cheeses, air-dried, aged, or fermented meats and salamis, pickled herring, spoiled meat, fava bean pods, tap and unpasteurized beer, concentrated yeast extract, sauerkraut, most soybean products, tyramine supplements, and chocolate; excessive caffeine is also listed, and alcohol is not recommended. A hypertensive emergency is described as, for example, blood pressure above 180/120 mm Hg with organ dysfunction, intracranial bleeding (sometimes fatal) has been reported, and blood pressure rises have also occurred without tyramine. Serotonin syndrome can occur with serotonergic drugs. Tranylcypromine is eliminated within 24 hours, but MAO activity takes up to 3 to 5 days to recover and inhibition may persist up to 10 days, and a washout period is required before starting another MAOI or a contraindicated antidepressant. The label reports abuse of PARNATE, in some cases in people with prior substance abuse, and dependence shown by withdrawal effects after abrupt discontinuation: delirium (even with low daily doses), restlessness, anxiety, confusion, hallucinations, headache, weakness, diarrhea, or rapid relapse into depression, plus thrombocytopenia and liver enzyme increases after withdrawal from high doses. Withdrawal effects appeared within 1 to 3 days and persisted for several weeks, and higher-than-recommended doses and longer use carried higher risk.

Participants / model

Adults with major depressive disorder not adequately responsive to other antidepressants; adults prescribed PARNATE, including postmarketing reports

Treatment

PARNATE film-coated oral tablets

Follow-up

Label version effective 2 July 2025

Study design

FDA prescribing information

Funding

not stated in the source

The label has no pharmacokinetics section beyond elimination within 24 hours and MAO recovery timing. Dosing, titration and washout day-counts are left out of this page.

Human study

Weber-Grandke H et al. Br J Clin Pharmacol. 1993;36(4):363-5. PMID 12959316.

After a single oral 20 mg dose of racemic tranylcypromine sulfate, exposure to the (-)-enantiomer far exceeded the (+)-enantiomer (mean AUC 197 versus 26 ng h/mL), and no conversion between enantiomers was detected. The two enantiomers are not interchangeable in exposure.

Participants / model

6 healthy subjects

Treatment

Oral racemic tranylcypromine sulfate 20 mg and single enantiomers 10 mg

Follow-up

Single doses

Study design

Clinical pharmacokinetic study

Funding

not stated in the source

A six-person study. The record reviewed reports no half-life.

FDA prescribing information

DailyMed, U.S. National Library of Medicine. PARNATE (tranylcypromine sulfate) film-coated oral tablets, prescribing information, label version effective 2 July 2025. Set ID b72d8187-dfcc-4ea0-b5e9-c0be95b69a27.

PARNATE is labeled for major depressive disorder in adults who have not responded adequately to other antidepressants; the label says it is not indicated for initial treatment because of the potential for serious adverse reactions and drug interactions and the need for dietary restrictions. A boxed warning covers suicidal thoughts and behaviors in children and young adults and hypertensive crisis with significant tyramine intake or certain drugs, during use or after stopping. The label names the active ingredient (+/-)-trans-2-phenylcyclopropylamine sulfate (2:1), a racemate, and expresses doses as tranylcypromine. It is not approved for pediatric use. The label contraindicates use with, or in rapid succession with, other MAOIs; SSRIs, SNRIs, tricyclics, and other antidepressants including bupropion and trazodone; amphetamines, methylphenidates, and derivatives; sympathomimetic products, including cold, hay fever, or weight-reducing products with pseudoephedrine, phenylephrine, or ephedrine and dietary supplements containing sympathomimetics; triptans; and individual drugs including buspirone, meperidine, tapentadol, dextromethorphan, tryptophan, SAM-e, levodopa, carbamazepine, cyclobenzaprine, and milnacipran. Pheochromocytoma is also a contraindication. High-tyramine foods and drinks are to be avoided during treatment and after stopping, including aged cheeses, air-dried, aged, or fermented meats and salamis, pickled herring, spoiled meat, fava bean pods, tap and unpasteurized beer, concentrated yeast extract, sauerkraut, most soybean products, tyramine supplements, and chocolate; excessive caffeine is also listed, and alcohol is not recommended. A hypertensive emergency is described as, for example, blood pressure above 180/120 mm Hg with organ dysfunction, intracranial bleeding (sometimes fatal) has been reported, and blood pressure rises have also occurred without tyramine. Serotonin syndrome can occur with serotonergic drugs. Tranylcypromine is eliminated within 24 hours, but MAO activity takes up to 3 to 5 days to recover and inhibition may persist up to 10 days, and a washout period is required before starting another MAOI or a contraindicated antidepressant. The label reports abuse of PARNATE, in some cases in people with prior substance abuse, and dependence shown by withdrawal effects after abrupt discontinuation: delirium (even with low daily doses), restlessness, anxiety, confusion, hallucinations, headache, weakness, diarrhea, or rapid relapse into depression, plus thrombocytopenia and liver enzyme increases after withdrawal from high doses. Withdrawal effects appeared within 1 to 3 days and persisted for several weeks, and higher-than-recommended doses and longer use carried higher risk.

Participants / model

Adults with major depressive disorder not adequately responsive to other antidepressants; adults prescribed PARNATE, including postmarketing reports

Treatment

PARNATE film-coated oral tablets

Follow-up

Label version effective 2 July 2025

Study design

FDA prescribing information

Funding

not stated in the source

The label has no pharmacokinetics section beyond elimination within 24 hours and MAO recovery timing. Dosing, titration and washout day-counts are left out of this page.

FDA prescribing information

DailyMed, U.S. National Library of Medicine. PARNATE (tranylcypromine sulfate) film-coated oral tablets, prescribing information, label version effective 2 July 2025. Set ID b72d8187-dfcc-4ea0-b5e9-c0be95b69a27.

PARNATE is labeled for major depressive disorder in adults who have not responded adequately to other antidepressants; the label says it is not indicated for initial treatment because of the potential for serious adverse reactions and drug interactions and the need for dietary restrictions. A boxed warning covers suicidal thoughts and behaviors in children and young adults and hypertensive crisis with significant tyramine intake or certain drugs, during use or after stopping. The label names the active ingredient (+/-)-trans-2-phenylcyclopropylamine sulfate (2:1), a racemate, and expresses doses as tranylcypromine. It is not approved for pediatric use. The label contraindicates use with, or in rapid succession with, other MAOIs; SSRIs, SNRIs, tricyclics, and other antidepressants including bupropion and trazodone; amphetamines, methylphenidates, and derivatives; sympathomimetic products, including cold, hay fever, or weight-reducing products with pseudoephedrine, phenylephrine, or ephedrine and dietary supplements containing sympathomimetics; triptans; and individual drugs including buspirone, meperidine, tapentadol, dextromethorphan, tryptophan, SAM-e, levodopa, carbamazepine, cyclobenzaprine, and milnacipran. Pheochromocytoma is also a contraindication. High-tyramine foods and drinks are to be avoided during treatment and after stopping, including aged cheeses, air-dried, aged, or fermented meats and salamis, pickled herring, spoiled meat, fava bean pods, tap and unpasteurized beer, concentrated yeast extract, sauerkraut, most soybean products, tyramine supplements, and chocolate; excessive caffeine is also listed, and alcohol is not recommended. A hypertensive emergency is described as, for example, blood pressure above 180/120 mm Hg with organ dysfunction, intracranial bleeding (sometimes fatal) has been reported, and blood pressure rises have also occurred without tyramine. Serotonin syndrome can occur with serotonergic drugs. Tranylcypromine is eliminated within 24 hours, but MAO activity takes up to 3 to 5 days to recover and inhibition may persist up to 10 days, and a washout period is required before starting another MAOI or a contraindicated antidepressant. The label reports abuse of PARNATE, in some cases in people with prior substance abuse, and dependence shown by withdrawal effects after abrupt discontinuation: delirium (even with low daily doses), restlessness, anxiety, confusion, hallucinations, headache, weakness, diarrhea, or rapid relapse into depression, plus thrombocytopenia and liver enzyme increases after withdrawal from high doses. Withdrawal effects appeared within 1 to 3 days and persisted for several weeks, and higher-than-recommended doses and longer use carried higher risk.

Participants / model

Adults with major depressive disorder not adequately responsive to other antidepressants; adults prescribed PARNATE, including postmarketing reports

Treatment

PARNATE film-coated oral tablets

Follow-up

Label version effective 2 July 2025

Study design

FDA prescribing information

Funding

not stated in the source

The label has no pharmacokinetics section beyond elimination within 24 hours and MAO recovery timing. Dosing, titration and washout day-counts are left out of this page.

Case report

Gahr M et al. Pharmacopsychiatry. 2013;46(4):123-9. PMID 23359339.

Delirium occurred in 13 of 25 published cases. All 18 patients in the withdrawal group had tranylcypromine abuse or dependence. Patients with delirium had higher mean prescribed doses (71.0 versus 38.3 mg a day) and actually taken doses (285.8 versus 187.7 mg a day), and effects began a mean of 1.9 to 2.2 days after stopping.

Participants / model

25 published case reports

Treatment

Oral tranylcypromine, often taken far above labeled doses

Follow-up

Effects began a mean of 1.9 to 2.2 days after stopping

Study design

Systematic review of case reports

Funding

not stated in the source

Case reports, so frequencies do not describe typical use.

Case report

Gahr M et al. Eur Neuropsychopharmacol. 2013;23(11):1364-72. PMID 23791433.

The review of 20 published poisonings found 10 deaths. Disturbed consciousness or cognitive dysfunction (90%), cardiovascular symptoms (55%), and hyperthermia (50%) were common, and 18 of 20 involved suicidal intent.

Participants / model

20 published poisoning cases

Treatment

Oral tranylcypromine overdose

Follow-up

not stated in the source

Study design

Systematic review of case reports

Funding

not stated in the source

Case reports of overdose, mostly with suicidal intent. Dose figures from the review are not reproduced here.

FDA prescribing information

DailyMed, U.S. National Library of Medicine. PARNATE (tranylcypromine sulfate) film-coated oral tablets, prescribing information, label version effective 2 July 2025. Set ID b72d8187-dfcc-4ea0-b5e9-c0be95b69a27.

PARNATE is labeled for major depressive disorder in adults who have not responded adequately to other antidepressants; the label says it is not indicated for initial treatment because of the potential for serious adverse reactions and drug interactions and the need for dietary restrictions. A boxed warning covers suicidal thoughts and behaviors in children and young adults and hypertensive crisis with significant tyramine intake or certain drugs, during use or after stopping. The label names the active ingredient (+/-)-trans-2-phenylcyclopropylamine sulfate (2:1), a racemate, and expresses doses as tranylcypromine. It is not approved for pediatric use. The label contraindicates use with, or in rapid succession with, other MAOIs; SSRIs, SNRIs, tricyclics, and other antidepressants including bupropion and trazodone; amphetamines, methylphenidates, and derivatives; sympathomimetic products, including cold, hay fever, or weight-reducing products with pseudoephedrine, phenylephrine, or ephedrine and dietary supplements containing sympathomimetics; triptans; and individual drugs including buspirone, meperidine, tapentadol, dextromethorphan, tryptophan, SAM-e, levodopa, carbamazepine, cyclobenzaprine, and milnacipran. Pheochromocytoma is also a contraindication. High-tyramine foods and drinks are to be avoided during treatment and after stopping, including aged cheeses, air-dried, aged, or fermented meats and salamis, pickled herring, spoiled meat, fava bean pods, tap and unpasteurized beer, concentrated yeast extract, sauerkraut, most soybean products, tyramine supplements, and chocolate; excessive caffeine is also listed, and alcohol is not recommended. A hypertensive emergency is described as, for example, blood pressure above 180/120 mm Hg with organ dysfunction, intracranial bleeding (sometimes fatal) has been reported, and blood pressure rises have also occurred without tyramine. Serotonin syndrome can occur with serotonergic drugs. Tranylcypromine is eliminated within 24 hours, but MAO activity takes up to 3 to 5 days to recover and inhibition may persist up to 10 days, and a washout period is required before starting another MAOI or a contraindicated antidepressant. The label reports abuse of PARNATE, in some cases in people with prior substance abuse, and dependence shown by withdrawal effects after abrupt discontinuation: delirium (even with low daily doses), restlessness, anxiety, confusion, hallucinations, headache, weakness, diarrhea, or rapid relapse into depression, plus thrombocytopenia and liver enzyme increases after withdrawal from high doses. Withdrawal effects appeared within 1 to 3 days and persisted for several weeks, and higher-than-recommended doses and longer use carried higher risk.

Participants / model

Adults with major depressive disorder not adequately responsive to other antidepressants; adults prescribed PARNATE, including postmarketing reports

Treatment

PARNATE film-coated oral tablets

Follow-up

Label version effective 2 July 2025

Study design

FDA prescribing information

Funding

not stated in the source

The label has no pharmacokinetics section beyond elimination within 24 hours and MAO recovery timing. Dosing, titration and washout day-counts are left out of this page.

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 012342 (PARNATE), with ANDA 040640. Dates read from the openFDA Drugs@FDA records.

FDA approved PARNATE under NDA 012342 on 21 February 1961; the application is now held by Advanz Pharma. A generic tranylcypromine sulfate tablet was approved under ANDA 040640 on 29 June 2006.

Participants / model

Not a clinical population

Treatment

Drug applications

Follow-up

Approvals in 1961 and 2006

Study design

FDA application records

Funding

not stated in the source

These records give approval dates and the current application holder. Indications come from the product label.

Systematic review and meta-analysis

Ricken R et al. Eur Neuropsychopharmacol. 2017;27(8):714-731. PMID 28579071.

Tranylcypromine was superior to placebo (pooled log odds ratio 0.509, 95% CI 0.026 to 0.993, 4 studies) and equal to other antidepressants (0.208, 95% CI -0.128 to 0.544, 10 studies). In depression resistant to tricyclics and SSRIs it was superior to placebo in one study (2.826, 95% CI 1.494 to 4.158) and to non-established antidepressants (1.976, 95% CI 0.907 to 3.045, 4 studies), and equal to other MAOIs and an antidepressant combination (-0.366, 95% CI -0.869 to 0.137, 4 studies). The authors cite controlled studies suggesting a particular advantage in atypical depression and note its third-line place in guidelines because of the tyramine-restricted diet.

Participants / model

Adults with depression, including treatment-resistant depression, in controlled trials

Treatment

Oral tranylcypromine

Follow-up

not stated in the source

Study design

Review with meta-analysis of controlled trials

Funding

not stated in the source

The atypical-depression advantage is cited by the authors from other controlled studies, not measured in this analysis.

Randomized controlled trial

McGrath PJ et al. Am J Psychiatry. 2006;163(9):1531-41; quiz 1666. PMID 16946177.

Remission rates were 6.9% on tranylcypromine (58 patients) and 13.7% on extended-release venlafaxine plus mirtazapine (51 patients), not significantly different. The mean exit dose of tranylcypromine was 36.9 mg, and tranylcypromine produced less symptom reduction and more attrition from intolerance.

Participants / model

109 adult outpatients with nonpsychotic major depression after three failed medication trials

Treatment

Oral tranylcypromine versus extended-release venlafaxine plus mirtazapine

Follow-up

not stated in the source

Study design

Open-label randomized trial; remission defined as HAM-D 7 or less

Funding

not stated in the source

Open-label, in people whose depression had not remitted after three prior medication trials.

PubMed search record

PubMed search run on 9 October 2026: tranylcypromine[tiab] AND (healthy OR volunteers OR volunteer)[tiab], 33 records returned; a second search for tranylcypromine with nootropic, cognitive enhancement, cognitive enhancer, smart drug, or neuroenhancement returned 9 records.

The healthy-volunteer search returned 33 records. They covered tyramine pressor testing, pharmacokinetics and assays, MAO inhibition, food and drug interactions, hormone levels, reviews, and unrelated laboratory work; none measured cognition, motivation, drive, or executive function. A second search for tranylcypromine with nootropic, cognitive enhancement, cognitive enhancer, smart drug, or neuroenhancement returned 9 records, all animal, in vitro, or assay work. No human study of tranylcypromine for cognitive or motivational enhancement in healthy people was found.

Participants / model

Records returned, not a population

Treatment

Not applicable

Follow-up

Searches run on 9 October 2026

Study design

Literature search

Funding

not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

FDA prescribing information

DailyMed, U.S. National Library of Medicine. PARNATE (tranylcypromine sulfate) film-coated oral tablets, prescribing information, label version effective 2 July 2025. Set ID b72d8187-dfcc-4ea0-b5e9-c0be95b69a27.

PARNATE is labeled for major depressive disorder in adults who have not responded adequately to other antidepressants; the label says it is not indicated for initial treatment because of the potential for serious adverse reactions and drug interactions and the need for dietary restrictions. A boxed warning covers suicidal thoughts and behaviors in children and young adults and hypertensive crisis with significant tyramine intake or certain drugs, during use or after stopping. The label names the active ingredient (+/-)-trans-2-phenylcyclopropylamine sulfate (2:1), a racemate, and expresses doses as tranylcypromine. It is not approved for pediatric use. The label contraindicates use with, or in rapid succession with, other MAOIs; SSRIs, SNRIs, tricyclics, and other antidepressants including bupropion and trazodone; amphetamines, methylphenidates, and derivatives; sympathomimetic products, including cold, hay fever, or weight-reducing products with pseudoephedrine, phenylephrine, or ephedrine and dietary supplements containing sympathomimetics; triptans; and individual drugs including buspirone, meperidine, tapentadol, dextromethorphan, tryptophan, SAM-e, levodopa, carbamazepine, cyclobenzaprine, and milnacipran. Pheochromocytoma is also a contraindication. High-tyramine foods and drinks are to be avoided during treatment and after stopping, including aged cheeses, air-dried, aged, or fermented meats and salamis, pickled herring, spoiled meat, fava bean pods, tap and unpasteurized beer, concentrated yeast extract, sauerkraut, most soybean products, tyramine supplements, and chocolate; excessive caffeine is also listed, and alcohol is not recommended. A hypertensive emergency is described as, for example, blood pressure above 180/120 mm Hg with organ dysfunction, intracranial bleeding (sometimes fatal) has been reported, and blood pressure rises have also occurred without tyramine. Serotonin syndrome can occur with serotonergic drugs. Tranylcypromine is eliminated within 24 hours, but MAO activity takes up to 3 to 5 days to recover and inhibition may persist up to 10 days, and a washout period is required before starting another MAOI or a contraindicated antidepressant. The label reports abuse of PARNATE, in some cases in people with prior substance abuse, and dependence shown by withdrawal effects after abrupt discontinuation: delirium (even with low daily doses), restlessness, anxiety, confusion, hallucinations, headache, weakness, diarrhea, or rapid relapse into depression, plus thrombocytopenia and liver enzyme increases after withdrawal from high doses. Withdrawal effects appeared within 1 to 3 days and persisted for several weeks, and higher-than-recommended doses and longer use carried higher risk.

Participants / model

Adults with major depressive disorder not adequately responsive to other antidepressants; adults prescribed PARNATE, including postmarketing reports

Treatment

PARNATE film-coated oral tablets

Follow-up

Label version effective 2 July 2025

Study design

FDA prescribing information

Funding

not stated in the source

The label has no pharmacokinetics section beyond elimination within 24 hours and MAO recovery timing. Dosing, titration and washout day-counts are left out of this page.

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 012342 (PARNATE), with ANDA 040640. Dates read from the openFDA Drugs@FDA records.

FDA approved PARNATE under NDA 012342 on 21 February 1961; the application is now held by Advanz Pharma. A generic tranylcypromine sulfate tablet was approved under ANDA 040640 on 29 June 2006.

Participants / model

Not a clinical population

Treatment

Drug applications

Follow-up

Approvals in 1961 and 2006

Study design

FDA application records

Funding

not stated in the source

These records give approval dates and the current application holder. Indications come from the product label.

Systematic review and meta-analysis

Ricken R et al. Eur Neuropsychopharmacol. 2017;27(8):714-731. PMID 28579071.

Tranylcypromine was superior to placebo (pooled log odds ratio 0.509, 95% CI 0.026 to 0.993, 4 studies) and equal to other antidepressants (0.208, 95% CI -0.128 to 0.544, 10 studies). In depression resistant to tricyclics and SSRIs it was superior to placebo in one study (2.826, 95% CI 1.494 to 4.158) and to non-established antidepressants (1.976, 95% CI 0.907 to 3.045, 4 studies), and equal to other MAOIs and an antidepressant combination (-0.366, 95% CI -0.869 to 0.137, 4 studies). The authors cite controlled studies suggesting a particular advantage in atypical depression and note its third-line place in guidelines because of the tyramine-restricted diet.

Participants / model

Adults with depression, including treatment-resistant depression, in controlled trials

Treatment

Oral tranylcypromine

Follow-up

not stated in the source

Study design

Review with meta-analysis of controlled trials

Funding

not stated in the source

The atypical-depression advantage is cited by the authors from other controlled studies, not measured in this analysis.

Randomized controlled trial

McGrath PJ et al. Am J Psychiatry. 2006;163(9):1531-41; quiz 1666. PMID 16946177.

Remission rates were 6.9% on tranylcypromine (58 patients) and 13.7% on extended-release venlafaxine plus mirtazapine (51 patients), not significantly different. The mean exit dose of tranylcypromine was 36.9 mg, and tranylcypromine produced less symptom reduction and more attrition from intolerance.

Participants / model

109 adult outpatients with nonpsychotic major depression after three failed medication trials

Treatment

Oral tranylcypromine versus extended-release venlafaxine plus mirtazapine

Follow-up

not stated in the source

Study design

Open-label randomized trial; remission defined as HAM-D 7 or less

Funding

not stated in the source

Open-label, in people whose depression had not remitted after three prior medication trials.

Randomized controlled trial

Himmelhoch JM et al. Am J Psychiatry. 1991;148(7):910-6. PMID 2053632.

Tranylcypromine produced lower attrition, greater symptom improvement, and higher global response than imipramine, without more treatment-emergent hypomania or mania. The authors link the advantage to anergia and reversed neurovegetative symptoms such as hypersomnia and hyperphagia.

Participants / model

56 outpatients with anergic bipolar I or II depression (28 per arm)

Treatment

Oral tranylcypromine versus imipramine

Follow-up

not stated in the source

Study design

Double-blind controlled trial

Funding

not stated in the source

The closest trial in these records to atypical or anergic presentations. It enrolled bipolar depression, not unipolar atypical depression.

Randomized controlled trial

Berlin I et al. Clin Pharmacol Ther. 1989;46(3):344-51. PMID 2673623.

Tyramine taken with a meal raised systolic pressure by 30 mm Hg at a mean of 1,200 mg (range 1,000 to 1,600) during placebo but at 35 mg (range 20 to 50) during tranylcypromine 10 mg twice daily, a factor of 38.2; moclobemide gave a factor of 5.0. The pressure rise lasted 126 minutes on tranylcypromine versus 69 on moclobemide.

Participants / model

16 healthy volunteers

Treatment

Oral tranylcypromine 10 mg twice daily; oral tyramine with meals

Follow-up

not stated in the source

Study design

Double-blind placebo-controlled parallel-group study

Funding

not stated in the source

A small healthy-volunteer study from 1988 or 1989. Thresholds in other people can differ.

Human study

Bieck PR et al. J Clin Psychopharmacol. 1988;8(4):237-45. PMID 3209716.

Unmedicated healthy volunteers needed 200 to 800 mg of tyramine to raise systolic pressure by 30 mm Hg. In 12 subjects on tranylcypromine for 8 to 16 days, tyramine sensitivity rose an estimated 56-fold, and full normalization of the pressor response took 30 days after the last dose. Systolic rises above 60 mm Hg occurred in 13% of all 296 tests in the program.

Participants / model

49 healthy volunteers, 12 of whom took tranylcypromine

Treatment

Oral tranylcypromine for 8 to 16 days; oral tyramine challenge

Follow-up

8 to 16 days of tranylcypromine; recovery followed for 30 days

Study design

Clinical pharmacology study with oral tyramine challenges

Funding

not stated in the source

A small healthy-volunteer study from 1988 or 1989.

Human study

Weber-Grandke H et al. Br J Clin Pharmacol. 1993;36(4):363-5. PMID 12959316.

After a single oral 20 mg dose of racemic tranylcypromine sulfate, exposure to the (-)-enantiomer far exceeded the (+)-enantiomer (mean AUC 197 versus 26 ng h/mL), and no conversion between enantiomers was detected. The two enantiomers are not interchangeable in exposure.

Participants / model

6 healthy subjects

Treatment

Oral racemic tranylcypromine sulfate 20 mg and single enantiomers 10 mg

Follow-up

Single doses

Study design

Clinical pharmacokinetic study

Funding

not stated in the source

A six-person study. The record reviewed reports no half-life.

Case report

Gahr M et al. Pharmacopsychiatry. 2013;46(4):123-9. PMID 23359339.

Delirium occurred in 13 of 25 published cases. All 18 patients in the withdrawal group had tranylcypromine abuse or dependence. Patients with delirium had higher mean prescribed doses (71.0 versus 38.3 mg a day) and actually taken doses (285.8 versus 187.7 mg a day), and effects began a mean of 1.9 to 2.2 days after stopping.

Participants / model

25 published case reports

Treatment

Oral tranylcypromine, often taken far above labeled doses

Follow-up

Effects began a mean of 1.9 to 2.2 days after stopping

Study design

Systematic review of case reports

Funding

not stated in the source

Case reports, so frequencies do not describe typical use.

Case report

Gahr M et al. Eur Neuropsychopharmacol. 2013;23(11):1364-72. PMID 23791433.

The review of 20 published poisonings found 10 deaths. Disturbed consciousness or cognitive dysfunction (90%), cardiovascular symptoms (55%), and hyperthermia (50%) were common, and 18 of 20 involved suicidal intent.

Participants / model

20 published poisoning cases

Treatment

Oral tranylcypromine overdose

Follow-up

not stated in the source

Study design

Systematic review of case reports

Funding

not stated in the source

Case reports of overdose, mostly with suicidal intent. Dose figures from the review are not reproduced here.

PubMed search record

PubMed search run on 9 October 2026: tranylcypromine[tiab] AND (healthy OR volunteers OR volunteer)[tiab], 33 records returned; a second search for tranylcypromine with nootropic, cognitive enhancement, cognitive enhancer, smart drug, or neuroenhancement returned 9 records.

The healthy-volunteer search returned 33 records. They covered tyramine pressor testing, pharmacokinetics and assays, MAO inhibition, food and drug interactions, hormone levels, reviews, and unrelated laboratory work; none measured cognition, motivation, drive, or executive function. A second search for tranylcypromine with nootropic, cognitive enhancement, cognitive enhancer, smart drug, or neuroenhancement returned 9 records, all animal, in vitro, or assay work. No human study of tranylcypromine for cognitive or motivational enhancement in healthy people was found.

Participants / model

Records returned, not a population

Treatment

Not applicable

Follow-up

Searches run on 9 October 2026

Study design

Literature search

Funding

not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Chemical identity record

National Library of Medicine. PubChem compound records CID 5530 (tranylcypromine) and CID 11473982 (tranylcypromine sulfate).

Tranylcypromine: PubChem CID 5530, C9H11N, 133.19 g/mol, named 2-phenylcyclopropan-1-amine without stereochemistry and listing several CAS-format synonyms (155-09-9, 54-97-7, 95-62-5). Tranylcypromine sulfate: CID 11473982, C18H24N2O4S, 364.5 g/mol, CAS 13492-01-8, but PubChem's computed name specifies the (1S,2R) form while the PARNATE label describes a racemate. Label doses are expressed as tranylcypromine.

Participants / model

Chemical identity, not a clinical population

Treatment

Base and sulfate salt

Follow-up

Not applicable

Study design

NLM chemical record

Funding

not stated in the source

PubChem's sulfate stereochemistry conflicts with the racemic label. Supplier products have not been compared with either record, so whether they are the racemate or a single enantiomer is unknown.