Tranylcypromine

Article Author:
Nina Parikh
Article Editor:
Abdolreza Saadabadi
Updated:
3/1/2020 12:25:16 PM
PubMed Link:
Tranylcypromine

Indications

The main FDA-approved indication of tranylcypromine is for major depressive disorder without melancholia. The non-FDA-approved indications for this medication include treatment-resistant depression, treatment-resistant social anxiety disorder, treatment-resistant panic disorder, and atypical depression. Atypical depression consists of hyperphagia, hypersomnia, rejection sensitivity, and leaden paralysis accompanying the depression.[1][2][3][4][5]

Mechanism of Action

Monoamine oxidase inhibitors (MAOIs) were discovered in 1952 and were the first class of antidepressants to be used clinically. Tranylcypromine was the second MAOI discovered. Originally, it was intended as a nasal decongestant. However, after it had failed as a nasal decongestant, it was found to be an effective antidepressant. Monoamine oxidase inhibitor is the enzyme that degrades neurotransmitters such as dopamine, norepinephrine, and serotonin. There are two types of monoamine oxidase inhibitors, MAOa and MAOb. MAOa breaks down serotonin and norepinephrine and is found mainly in the gut. MAOb metabolizes phenylethylamine and is present in high concentration in the basal ganglia and platelets. Both MAOa and MAOb break down dopamine. This drug is mostly a nonhydrazine irreversible inhibitor of MAOa and is also an irreversible inhibitor of MAOb but to a lesser degree. Tranylcypromine also blocks the reuptake of catecholamines and serotonin. As a result, the levels of norepinephrine, epinephrine, serotonin, and dopamine increase. Tranylcypromine is also structurally similar to amphetamine, which may contribute to the reason why this drug has some stimulant-like effects. The onset of action for this drug is typically 2 to 4 weeks, and the duration is approximately 10 to 21 days.

Administration

This medication comes in a 10 mg oral tablet. It is also has a generic form available. The therapeutic dose is 30 mg/day in divided doses. The starting dose of tranylcypromine is usually 10 mg daily. The dose can then be titrated up to 30 mg daily. If the dosage needs to be titrated even further, after two weeks, the dose can be increased by 10 mg every 1 to 3 weeks until the maximum dosage of 60 mg daily is reached.

Adverse Effects

Common side effects of tranylcypromine include dry mouth, headaches, diarrhea, urinary hesitancy, insomnia, agitation, anxiety, nausea, and sexual dysfunction. Postural hypotension, sometimes leading to syncope, is another common side effect, which warrants special attention to elderly patients on this medication. This side effect is noted to be dose-related and may require splitting the dose into 3 to 4 doses each day. More serious side effects include hepatotoxicity, seizures, and induction of mania. Additionally, in the United States, there is a black-box warning stating that this medication may lead to the activation of suicidal ideation and behavior in children, adolescents, and young adults aged 18 to 24 years of age with major depressive disorder and other psychiatric disorders. It is important to monitor these patients during the first 1 to 2 months of treatment and when adjusting the dosage of this medication. A transient rise in blood pressure can also occur after dosing, but usually, resolves within 3 to 4 hours. This medication is less likely to cause weight gain in patients, and some patients may even experience weight loss. This MAOI runs the risk of hypertensive crisis, especially if it interacts with other sympathomimetics. Hypertensive crisis, severe increases in diastolic blood pressure more than 120 mmHg, will present with an occipital headache first followed by confusion, chest pain, blurred vision, nausea, vomiting, shortness of breath, palpitations, anxiety or seizures. A special diet limited in tyramine is an absolute necessity in those patients taking an MAOI to avoid a hypertensive crisis. When the MAOIs inactivate the MAO enzymes, the norepinephrine release by tyramine is not able to be properly broken down either, potentially resulting in high circulating levels of norepinephrine in the blood. High blood levels of norepinephrine released by tyramine can lead to dangerous levels of increased blood pressure. Dietary tyramine as low as 10 mg can cause an increase in blood pressure in the presence of an MAOI. Some of the most important food and drink items that patients are not allowed to consume includes all aged cheeses, all aged/smoked/pickled/cured meats/fish/poultry, sourdough bread, soy products, fava beans, over-ripened avocado, soy sauce, and tap/draft beers. There is also the risk of serotonin syndrome due to the interaction of this medication with other serotonergic medications.  Serotonin syndrome results from the build-up of too much serotonin. The Sternbach criteria for assessing serotonin toxicity include the recent addition of or increase in a serotonergic agent, absence of other etiologies, no recent addition of or increase of a neuroleptic agent and at least three of the following:

  • Agitation
  • Myoclonus
  • Hyperreflexia
  • Diaphoresis
  • Shivering
  • Tremor
  • Diarrhea
  • Ataxia or incoordination
  • Fever.

If the patient decides to switch from a serotonin reuptake inhibitor (SSRI) to MAOI, the SSRI should be stopped at least five half-lives depending on each drug, which usually is 10 to 14 days, before starting the MAOI. If the patient is switching from fluoxetine specifically, they should wait at least five weeks due to fluoxetine’s long half-life; this will prevent hypertensive crisis and serotonin syndrome from occurring. If the patient is switching from an MAOI to an SSRI, they must wait at least two weeks.[6][7][8]

Contraindications

Patients must not use tranylcypromine if they are currently taking meperidine, fentanyl, guanethidine, diuretics, dextromethorphan, buspirone, bupropion, sympathomimetic, or L- tryptophan. Additionally, patients should not be concurrently on another MAOI or any medications that could inhibit serotonin reuptake, including SSRIs, sibutramine, tramadol, milnacipran, duloxetine, venlafaxine, clomipramine, and others. If the patient has pheochromocytoma, cardiovascular or cerebrovascular disease, history of liver disease, or frequent or severe headaches, they should not take tranylcypromine. If a patient is undergoing surgery that requires the administration of general anesthesia, avoid this medication. Patients must be not on any prohibited substance. Patients must be able to follow a low-tyramine diet and must not have any history of allergy to tranylcypromine.

Monitoring

Monitoring parameters for this medication include renal function, hepatic function, heart rate, blood pressure, blood glucose, mental status, worsening depression, suicidality, or unusual behavioral changes. It is essential to prescribe this medication to only those patients who can be monitored closely and frequently.

Toxicity

Toxic doses of this medication are possible if the dosage exceeds 60 mg/day; the lethal dose is 75 mg/kg. There have been 20 acute overdoses and ten fatalities from tranylcypromine. If the patient takes this drug at toxic doses, you will see dizziness, sedation, insomnia, restlessness, headache, ataxia, cardiovascular effects, respiratory depression, or coma in your patient. A case report from January 2017 revealed that amphetamine and methamphetamine appeared in the urine of a patient who had suffered from a fatal tranylcypromine overdose. This finding brings into question and prompts further research investigating the breakdown of tranylcypromine into amphetamine and methamphetamine and the dangers that can impose.

Enhancing Healthcare Team Outcomes

All healthcare workers, including nurse practitioners who prescribe tranylcypromine, should be fully aware of its side effect profile and the rigid dietary requirements. Numerous litigations have occurred in the past because of the failure to educate the patient. To be on the safe side, this medication is best avoided as there are many other safer options.


References

[1] Wang X,Su M,Li Y,Liu T,Wang Y,Chen Y,Tang L,He YP,Ding X,Yu F,Shen J,Li J,Zhou Y,Chen YL,Xiong B, Tranylcypromine and 6-trifluoroethyl thienopyrimidine hybrid as LSD1 inhibitor. Bioorganic     [PubMed PMID: 30713023]
[2] Zugliani MM,Cabo MC,Nardi AE,Perna G,Freire RC, Pharmacological and Neuromodulatory Treatments for Panic Disorder: Clinical Trials from 2010 to 2018. Psychiatry investigation. 2019 Jan;     [PubMed PMID: 30696238]
[3] Shalom Feinberg S, Spontaneous MAOI hypertensive reaction, not likely armodafinil -tranylcypromine interaction. Journal of the neurological sciences. 2019 Jan 9;     [PubMed PMID: 30654092]
[4] van der Heide D,Merckelbach H,van Harten P, [Tranylcypromine and khat: a potentially fatal combination]. Tijdschrift voor psychiatrie. 2018;     [PubMed PMID: 30132583]
[5] Ferreira-Garcia R,da Rocha Freire RC,Appolinário JC,Levitan MN,Halkjær-Lassen RD,Bueno JR,Nardi AE, Tranylcypromine Plus Amitriptyline for Electroconvulsive Therapy-Resistant Depression: A Long-Term Study. Journal of clinical psychopharmacology. 2018 Oct;     [PubMed PMID: 30106881]
[6] Kinslow CJ,Shapiro SD,Grunebaum MF,Miller EC, Acute hypertensive crisis and severe headache after concurrent use of armodafinil and tranylcypromine: Case report and review of the literature. Journal of the neurological sciences. 2018 Oct 15;     [PubMed PMID: 30077942]
[7] Tranylcypromine 2006;     [PubMed PMID: 30000232]
[8] Ulrich S,Ricken R,Adli M, Tranylcypromine in mind (Part I): Review of pharmacology. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2017 Aug;     [PubMed PMID: 28655495]