Tranylcypromine (Parnate)

Primer

Tranylcypromine (Trade name: Parnate), also known as trans-2-phenylcyclopropylamine, is an antidepressant in the irreversible monoamine oxidase inhibitor (MAOI) class used in the treatment of major depressive disorder.

Pharmacokinetics

See also article: Introduction to Pharmacology

Pharmacokinetics of Tranylcypromine

Absorption	Rapidly absorbed from the GI tract following oral administration. Peak plasma concentrations occur within 1 hour of dosing.
Distribution	Distributed widely throughout the body.
Metabolism	Liver; Phase I metabolism
Elimination	Excreted in the urine, mainly in the form of metabolites
Half-life	Although the half-life is only about 2 hours, the pharmacodynamic effects last several days to 1 week due to irreversible inhibition of MAO.^[1]

See also article: Cytochrome (CYP) P450 Metabolism

Tranylcypromine: Cytochrome P450 Metabolism

Substrate of (Metabolized by)	-
Induces	-
Inhibits	CYP 2A6

Pharmacodynamics

Mechanism of Action

Monoamine oxidase (MAO) is the enzyme that degrades neurotransmitters including dopamine, norepinephrine, and serotonin.
- MAO-A breaks down serotonin and norepinephrine and is found mainly in the gut.
- MAO-B metabolizes phenylethylamine and is present in high concentrations in the basal ganglia and platelets
- Both MAOA and MAOB break down dopamine
Tranylcypromine is mainly a non-hydrazine irreversible inhibitor of MAOA and is also an irreversible inhibitor of MAO-B but to a lesser degree.
Tranylcypromine thus increases levels of norepinephrine, epinephrine, serotonin, and dopamine.
- Tranylcypromine is also structurally similar to amphetamine, which may contribute to stimulant-like effects.

Toxicity

At toxic doses, individuals can experience dizziness, sedation, insomnia, restlessness, headache, ataxia, cardiovascular effects, respiratory depression, or coma.

Indications

Major depressive disorder

Dosing

Dosing for Tranylcypromine

Starting	10 mg PO daily
Titration	Increase by 10 mg every 1 to 3 weeks (may need to take in divided doses to manage side effects)
Maximum	60 mg PO daily
Taper	Generally can taper within a few weeks (make sure to not overlap with other antidepressants for at least

Formulations

Tranylcypromine comes in oral tablet formulation

Monitoring

Blood pressure should be monitored during treatment
Tranylcypromine increases the risk for a hypertensive crisis, especially if it interacts with other sympathomimetics.

Contraindications

Absolute

Meperidine, fentanyl, guanethidine, dextromethorphan, buspirone, bupropion, sympathomimetic, or L- tryptophan.
Patients should not be on another MAOI currently or any medications that could inhibit serotonin reuptake, including SSRIs, sibutramine, tramadol, milnacipran, duloxetine, venlafaxine, clomipramine, and other serotonergic psychotropics.
Medical conditions including pheochromocytoma, cardiovascular or cerebrovascular disease, history of liver disease, or frequent or severe headaches.

Relative

Individuals with upcoming procedures or surgery that requires the administration of general anesthesia are sometimes recommended to discontinue MAOIs for 2 weeks the procedure.
Patients must be able to follow a low-tyramine diet.

Drug-Drug Interactions

Most SSRIs require 2 weeks of washout before starting an MAOI
- Fluoxetine, however, because of its long half-life, requires a minimum of 5 weeks.^[2]

Side Effects

Side effects are dose-related so some patients may require splitting the dose into 3 to 4 doses each day to manage these side effects
Common side effects include dry mouth, headaches, diarrhea, urinary hesitancy, insomnia, agitation, anxiety, nausea, and sexual dysfunction.
- Postural hypotension, sometimes leading to syncope, is an important side effect to consider in the geriatric population
Increasing doses of tranylcypromine can increase supine blood pressure but not standing diastolic blood pressure.^[3]
- Note that this is separate from the tyramine-induced hypertensive crisis that can occur in MAOIs.

Adverse Events

Serotonin syndrome
The risk of severe cerebrovascular events associated with hypertensive reactions has been estimated to be 1.4 to 7.0 per 100 000 individuals treated with tranylcypromine.^[4]

Clinical Pearls

See also: Lafrenière, S., & Blier, P. (2022). Medical assistance in living after failure of ECT and ketamine. Journal of Psychiatry & Neuroscience: JPN, 47(5), E323.

The short half-life of tranylcypromine may be advantageous for use in older adults.

Special Populations

Geriatric

See main article: Geriatric Pharmacology

Pediatric

See main article: Pediatric Pharmacology

Obstetric and Fetal

See main article: Obstetric and Fetal Pharmacology

Medically Ill

See main article: Psychotropic Dosing in the Medically Ill

Resources

Parikh, N., Yilanli, M., & Saadabadi, A. (2017). Tranylcypromine.

¹⁾ Ulrich, S., Ricken, R., & Adli, M. (2017). Tranylcypromine in mind (Part I): Review of pharmacology. European Neuropsychopharmacology, 27(8), 697-713.

²⁾ Palaniyappan, L., Insole, L., & Ferrier, N. (2009). Combining antidepressants: a review of evidence. Advances in psychiatric treatment, 15(2), 90-99.

³⁾ Keck, P. E., Carter, W. P., Nierenberg, A. A., Cooper, T. B., Potter, W. Z., & Rothschild, A. J. (1991). Acute cardiovascular effects of tranylcypromine: correlation with plasma drug, metabolite, norepinephrine, and MHPG levels. The Journal of clinical psychiatry.

⁴⁾ Lafrenière, S., & Blier, P. (2022). Medical assistance in living after failure of ECT and ketamine. Journal of Psychiatry & Neuroscience: JPN, 47(5), E323.

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