- Last edited on September 20, 2022
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. |
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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) | - |
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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
Dosing
Dosing for Tranylcypromine
Starting | 10 mg PO daily |
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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
- 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
- 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
References
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.