tranylcypromine

Actions and Spectrum: 

tranylcypromine is a monoamine oxidase inhibitor (MAOI) primarily used to treat major depressive disorder. It works by inhibiting the activity of monoamine oxidase, an enzyme that breaks down neurotransmitters such as serotonin, norepinephrine, and dopamine. This results in increased levels of these neurotransmitters in the brain, which can help alleviate depressive symptoms. 

The spectrum of actions of tranylcypromine includes: 

• Antidepressant effects: tranylcypromine is primarily used to treat major depressive disorder and effectively relieves depressive symptoms in many patients. 
• Anxiolytic effects: tranylcypromine may also have anxiolytic effects, which can reduce anxiety in some patients. 
• Anti-obsessional effects: tranylcypromine may also effectively treat obsessive-compulsive disorder (OCD) and other related disorders. 
• Anti-panic effects: tranylcypromine may also help reduce some patients’ panic attacks’ frequency and severity. 
• Antiaggressive effects: tranylcypromine may also have anti-aggressive effects, which have been used to treat impulsive aggression. 

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency not defined 

Drowsiness 

Sleep disturbance 

Fatigue 

Orthostatic hypotension 

Dizziness 

Headache 

Weakness 

Tremor 

Hyperreflexia 

Confusion 

Decreased memory 

Nystagmus 

Constipation 

Dry mouth 

Paresthesia 

Anorexia 

Impotence 

Irritation 

Hypomania 

Hypermetabolic syndrome 

Urinary frequency or retention 

Anxiety 

Arthralgia 

Edema 

SIADH 

Jaundice 

Visual disturbance  

Ataxia 

Seizure 

Black Box Warning: 

tranylcypromine increases the risk of suicidal thoughts and alters behavior in young adults. The drug is not meant for pediatrics. 

Contraindication/Caution: 

tranylcypromine has several contraindications and precautions to be considered before prescribing or taking the medication. These include: 

• Contraindications with other medications: tranylcypromine should not be taken with other antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants, due to the risk of serotonin syndrome. Additionally, it should not be taken with stimulants, such as amphetamines or cocaine, or with certain pain medications, such as meperidine. 
• Hypertensive crisis: tranylcypromine can cause a hypertensive crisis, a severe increase in blood pressure that can lead to a stroke or heart attack. This can occur if the medication is taken with certain foods or drinks that contain tyramine, such as aged cheeses, cured meats, and some alcoholic beverages. It is essential to avoid these foods and drinks while taking tranylcypromine. 
• Cardiovascular disease: tranylcypromine should be used with caution in patients with a history of cardiovascular disease, including hypertension, angina, or heart failure 
• Liver disease: tranylcypromine should be used cautiously in patients with liver disease, as the liver primarily metabolizes it and may accumulate in the body in patients with impaired liver function. 
• Pregnancy and breastfeeding: tranylcypromine should be used cautiously in pregnant or breastfeeding women, as there is limited data on its safety in these populations. 
• Other medical conditions: tranylcypromine should be used cautiously in patients with other medical conditions, including diabetes, hyperthyroidism, and epilepsy, as it can exacerbate these conditions. 

Pregnancy consideration:  

No data available for utilization in pregnant women 

Breastfeeding warnings:  

Drug distribution in breast milk is unknown, so use the drug cautiously during lactation. 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: No evidence of risk to the fetus is found in animal reproduction studies, and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a human product; Pregnant women must take care of the potential risks. 
• Category D: There is adequate data with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergencies for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. The drug is not for pregnant women. 
• Category N: No data for the drug under this category is available. 

Pharmacology: 

tranylcypromine is a monoamine oxidase inhibitor (MAOI) that irreversibly inhibits the activity of monoamine oxidase (MAO) enzymes, specifically MAO-A and MAO-B, in the central nervous system. These enzymes break down neurotransmitters such as serotonin, norepinephrine, and dopamine, which regulate mood, anxiety, and other emotional states. 

By inhibiting the breakdown of these neurotransmitters, tranylcypromine increases their availability in the brain, leading to increased activity of these pathways and a reduction in depressive symptoms. This effect is thought to be due to the increase in the levels of these neurotransmitters, which can enhance mood, increase energy levels, and improve motivation and pleasure. 

Pharmacodynamics: 

The pharmacodynamics of tranylcypromine primarily involve its inhibition of monoamine oxidase (MAO) enzymes, which increases neurotransmitters such as serotonin, norepinephrine, and dopamine levels in the brain. This increase in neurotransmitter levels can have several effects on the central nervous system, including: 

• Antidepressant effects: By increasing the availability of neurotransmitters involved in mood regulation, tranylcypromine can reduce symptoms of depression, such as low mood, lack of energy, and loss of pleasure. 
• Anxiolytic effects: Increased neurotransmitters such as serotonin and norepinephrine can also have anxiolytic effects, reducing symptoms of anxiety and tension. 
• Cognitive effects: Increased dopamine levels can improve cognitive function, including memory, attention, and motivation. 
• Cardiovascular effects: tranylcypromine can cause an increase in blood pressure due to its inhibition of MAO-A enzymes, which break down norepinephrine in the blood vessels. This can lead to vasoconstriction and an increase in blood pressure. 
• Adverse effects: tranylcypromine can also have several adverse effects, including insomnia, agitation, nausea, and tremors, which may be related to its effects on other neurotransmitter systems, such as the histaminergic and cholinergic systems. 

Pharmacokinetics: 

Absorption 

tranylcypromine is rapidly and completely absorbed after oral administration, with peak plasma concentrations reached within 1-2 hours.  

Distribution 

The bioavailability of tranylcypromine is approximately 100%, meaning that all the drug taken orally reaches systemic circulation. 

It is highly bound to plasma proteins, with approximately 90% of the drug bound to albumin. 

Metabolism 

tranylcypromine is extensively metabolized in the liver by the cytochrome P450 enzyme system, primarily by the CYP2A6 and CYP2C19 enzymes. The primary metabolite is phenylacetic acid, which is excreted in the urine. Other metabolites include amphetamine and methamphetamine, which can lead to false positive results in drug tests. 

Elimination and Excretion 

tranylcypromine has a short elimination half-life of around 2-3 hours, but its effects can persist for several weeks due to its irreversible inhibition of monoamine oxidase enzymes. As new MAO enzymes are synthesized, the effects of tranylcypromine will gradually dissipate, although this process may take several weeks. 

tranylcypromine is eliminated primarily by renal excretion of its metabolites, with approximately 60-70% of the dose excreted in the urine within 24 hours. The remaining 30-40% is excreted in the feces. 

tranylcypromine has a low volume of distribution, indicating that it is primarily distributed in the plasma and extracellular fluid.

Administration: 

tranylcypromine is typically administered orally as a tablet or capsule, with doses ranging from 10 to 60 mg daily. The recommended starting dose is usually 10 mg once or twice a day, gradually increasing over several weeks to a maximum of 60 mg per day if needed. 

tranylcypromine should be taken with food to reduce the risk of gastrointestinal side effects. It is essential to avoid foods and beverages that contain high levels of tyramine while taking tranylcypromine, as this can cause a potentially life-threatening hypertensive crisis. Foods and beverages to avoid include aged cheeses, cured meats, pickled or fermented foods, beer, red wine, and certain fruits and vegetables. 

tranylcypromine should be used with caution in patients with cardiovascular disease, hypertension, or seizure disorders, as it can cause an increase in blood pressure or worsen seizures. It should also be used cautiously in patients taking other medications that can interact with tranylcypromine, such as other MAO inhibitors, sympathomimetic agents, and certain antidepressants. 

tranylcypromine should not be abruptly discontinued, as this can lead to withdrawal symptoms such as depression, anxiety, and insomnia. Instead, the dose should be gradually tapered off over several weeks under the supervision of a healthcare provider. 

Patient information leaflet 

Generic Name:  tranylcypromine 

Pronounced: TRAN-il-SIP-roe-meen 

Why do we use tranylcypromine? 

tranylcypromine is used primarily as an antidepressant medication for treating major depressive disorder, particularly when other antidepressants have been ineffective or poorly tolerated. It is a member of the class of drugs known as monoamine oxidase inhibitors (MAOIs), which work by inhibiting the enzyme monoamine oxidase (MAO), thereby increasing neurotransmitter levels such as serotonin, norepinephrine, and dopamine in the brain. tranylcypromine has also been used off-label to treat other conditions, such as anxiety, panic, and social phobia.