Usage
- Tranylcypromine is primarily indicated for the treatment of major depressive disorder (MDD), particularly in cases where other antidepressant medications have proven ineffective. It may also be used off-label for conditions like obsessive-compulsive disorder (OCD), seasonal affective disorder, and social phobia.
- Pharmacological Classification: Monoamine oxidase inhibitor (MAOI).
- Mechanism of Action: Tranylcypromine irreversibly inhibits both monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B), enzymes responsible for breaking down neurotransmitters like dopamine, norepinephrine, and serotonin. This leads to increased levels of these neurotransmitters in the brain, which are believed to play a crucial role in mood regulation. It also blocks the reuptake of these neurotransmitters, further contributing to their elevated levels. Additionally, its structural similarity to amphetamine may contribute to its stimulant-like effects.
Alternate Names
- International Nonproprietary Name (INN): Tranylcypromine
- Brand Name: Parnate
How It Works
- Pharmacodynamics: Tranylcypromine elevates levels of dopamine, norepinephrine, and serotonin in the brain by inhibiting MAO-A and MAO-B, resulting in improved mood and alleviation of depressive symptoms. Its amphetamine-like structure may contribute to its stimulant effects.
- Pharmacokinetics:
- Absorption: Tranylcypromine is well-absorbed orally.
- Metabolism: The metabolic pathways are not fully elucidated, but research suggests potential breakdown into amphetamine and methamphetamine, although the clinical significance of this requires further investigation.
- Elimination: The precise elimination pathways are not fully defined in the provided sources.
- Mode of Action: Tranylcypromine irreversibly binds to and inhibits MAO-A and MAO-B, preventing the breakdown of dopamine, norepinephrine, and serotonin. This results in an accumulation of these neurotransmitters in the synaptic cleft, increasing their availability to interact with postsynaptic receptors.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Tranylcypromine’s primary action is the irreversible inhibition of MAO-A and MAO-B. It also inhibits the reuptake of dopamine, serotonin, and norepinephrine.
- Elimination Pathways: Although not fully detailed in the sources, information suggests both renal and hepatic involvement in the drug’s elimination.
Dosage
Standard Dosage
Adults:
- Initial: 20 mg/day (10 mg in the morning and 10 mg in the afternoon). If no response is observed within 2-3 weeks, increase to 30 mg/day (20 mg in the morning and 10 mg in the afternoon). Further increases can be made in 10 mg increments every 1-3 weeks up to a maximum of 60 mg/day, divided into two doses. Maintenance dosage: Usually 10 mg/day once a response is obtained. Another dosing regimen suggests starting at 15 mg every 12 hours, increasing in 5 mg increments every 1-3 weeks as needed, not to exceed 60 mg per day.
Children: Use is not recommended.
Special Cases:
- Elderly Patients: Start at a lower dose (e.g., 10 mg/day) and increase cautiously, as elderly patients may be more susceptible to side effects like orthostatic hypotension.
- Patients with Renal Impairment: Exercise caution and consider dose adjustments.
- Patients with Hepatic Dysfunction: Exercise caution and consider dose adjustments.
- Patients with Comorbid Conditions: Careful monitoring and dose adjustments may be necessary for patients with conditions like diabetes, cardiovascular disease, epilepsy, hyperthyroidism, or a history of drug or alcohol dependence.
Clinical Use Cases
Tranylcypromine does not have a specific indicated use for the conditions you mentioned, it’s important to clarify. The scenarios below like intubation, surgical procedures, mechanical ventilation and ICU are more relevant to anesthetic and other critical care medications.
Dosage Adjustments
Dose adjustments may be necessary based on individual patient response, tolerability, renal or hepatic function, and the presence of comorbid conditions. Close monitoring of blood pressure, heart rate, blood glucose, liver and kidney function, and mental status is essential.
Side Effects
Common Side Effects:
Dry mouth, dizziness, insomnia, drowsiness, weakness, loss of appetite, diarrhea, constipation, stomach pain, blurred vision, chills, ringing in the ears, muscle tightening or jerking, uncontrollable shaking, numbness, burning or tingling in the extremities, difficulty urinating, decreased sexual ability, hair loss, rash.
Rare but Serious Side Effects:
Hypertensive crisis (sudden, severe headache, nausea, vomiting, stiff neck, fast or irregular heartbeat), serotonin syndrome (mental status changes, autonomic instability, neuromuscular hyperactivity), liver damage (right upper belly pain, loss of appetite, nausea, light-colored stool, dark urine, jaundice), suicidal thoughts and behaviors, mania or hypomania, orthostatic hypotension.
Long-Term Effects:
Potential long-term effects may include dependence, withdrawal symptoms upon discontinuation (irritability, nausea, dizziness, vomiting, nightmares, headache, paresthesia), and chronic complications related to untreated underlying conditions.
Adverse Drug Reactions (ADR):
Clinically significant ADRs include hypertensive crisis, serotonin syndrome, liver injury, severe allergic reactions, and suicidal ideation. These reactions require immediate medical intervention.
Contraindications
Absolute contraindications include pheochromocytoma, other catecholamine-releasing paragangliomas, concurrent use of MAOIs or serotonin reuptake inhibitors (SSRIs, SNRIs, TCAs within 14 days – 5 weeks for fluoxetine), and hypersensitivity to tranylcypromine. Relative contraindications include cardiovascular or cerebrovascular disease, severe liver or kidney disease, history of seizures, hyperthyroidism, and uncontrolled hypertension.
Drug Interactions
Tranylcypromine interacts with numerous medications, including other antidepressants (SSRIs, SNRIs, TCAs), MAOIs, sympathomimetics (e.g., ephedrine, pseudoephedrine), certain analgesics (e.g., meperidine, tramadol), some antihypertensives (e.g., methyldopa), and certain foods containing tyramine. It can also interact with alcohol, OTC drugs, and herbal supplements. Refer to a comprehensive drug interaction database for detailed information as there are a significant number of interactions that cannot be comprehensively listed within this format.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not assigned. Limited data are available, but potential risks include placental infarction and congenital anomalies. Generally, MAOI use is discouraged during pregnancy due to the risk of maternal hypertensive crisis.
- Breastfeeding: Tranylcypromine passes into breast milk. Breastfeeding is contraindicated due to the potential for serious adverse reactions in the infant.
Drug Profile Summary
- Mechanism of Action: Irreversible MAO-A and MAO-B inhibition, increasing levels of dopamine, norepinephrine, and serotonin; also inhibits reuptake of these neurotransmitters.
- Side Effects: Dry mouth, dizziness, insomnia, postural hypotension; rarely, hypertensive crisis, serotonin syndrome, liver damage, suicidal thoughts.
- Contraindications: Pheochromocytoma, concurrent use of MAOIs or serotonin reuptake inhibitors.
- Drug Interactions: Numerous drug interactions, including other antidepressants, sympathomimetics, and tyramine-containing foods.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: Initially 20 mg/day, increasing as needed up to 60 mg/day; Children: Not recommended.
- Monitoring Parameters: Blood pressure, heart rate, blood glucose, liver and renal function, mental status.
Popular Combinations
Combining tranylcypromine with other antidepressants is generally contraindicated due to the risk of serotonin syndrome. Some clinicians have reported using tranylcypromine in combination with mirtazapine or amitriptyline in treatment-resistant depression, but this practice carries significant risks and requires careful monitoring.
Precautions
- General Precautions: Pre-screening for allergies, cardiovascular disease, liver or renal dysfunction, and drug interactions is essential.
- Specific Populations: Pregnant and breastfeeding women should not take tranylcypromine. Use with caution in elderly patients and those with renal or hepatic impairment. Pediatric use is not recommended.
- Lifestyle Considerations: Avoid alcohol and tyramine-rich foods. Caution regarding driving and operating machinery due to potential drowsiness and dizziness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Tranylcypromine?
A: Adults: Initial dose is typically 20mg/day, divided into two doses. This may be increased gradually as needed up to a maximum of 60 mg/day based on patient response. Children: Use is not recommended. Elderly patients: Initiate therapy at a lower dose and titrate cautiously.
Q2: What are the common side effects of Tranylcypromine?
A: Common side effects include dry mouth, dizziness, insomnia, postural hypotension, drowsiness, constipation, and blurred vision.
Q3: What are the serious side effects of tranylcypromine?
A: Serious side effects include hypertensive crisis, serotonin syndrome, and liver damage. These warrant immediate medical attention.
Q4: What foods should be avoided while taking tranylcypromine?
A: Foods high in tyramine should be avoided, including aged cheeses, cured meats, fermented foods, and certain alcoholic beverages. This is to prevent hypertensive crisis.
Q5: Can Tranylcypromine be taken with other antidepressants?
A: Combining tranylcypromine with other antidepressants, particularly SSRIs, SNRIs, and TCAs, is generally contraindicated due to the high risk of serotonin syndrome.
Q6: What are the signs of a hypertensive crisis?
A: Signs of a hypertensive crisis include a sudden, severe headache, nausea, vomiting, stiff neck, rapid or irregular heartbeat, sweating, and visual disturbances.
Q7: What should I do if I miss a dose of Tranylcypromine?
A: Take the missed dose as soon as you remember, unless it is close to the time for your next dose. Do not double the dose to catch up.
Q8: Can Tranylcypromine be used during pregnancy or breastfeeding?
A: Tranylcypromine is contraindicated during pregnancy and breastfeeding due to potential risks to the fetus/infant.
Q9: How long does it take for Tranylcypromine to start working?
A: It typically takes 2-4 weeks for tranylcypromine to produce a noticeable improvement in depressive symptoms.
Q10: What are the withdrawal symptoms associated with stopping Tranylcypromine?
A: Abrupt discontinuation can lead to withdrawal symptoms such as irritability, nausea, dizziness, vomiting, nightmares, headache, and paresthesia. It should be tapered off gradually under medical supervision.
