isocarboxazid

Actions and Spectrum: 

isocarboxazid is a medication that belongs to a class of drugs known as monoamine oxidase inhibitors (MAOIs). It is primarily used to treat depression and can also be used to treat anxiety and other psychiatric conditions. 

The action of isocarboxazid involves the inhibition of the enzyme monoamine oxidase, which is responsible for breaking down neurotransmitters such as serotonin, dopamine, and norepinephrine in the brain. By inhibiting this enzyme, isocarboxazid increases the levels of these neurotransmitters in the brain, which can help to improve mood and reduce symptoms of depression and anxiety. 

The spectrum of isocarboxazid is primarily focused on treating depression, but it can also be used to treat other psychiatric conditions, such as anxiety and panic disorders. It is not recommended for use in individuals with a history of liver disease or those taking other medications that can interact with MAOIs, including certain antidepressants, opioids, and stimulants. 

It is important to note that isocarboxazid can have significant side effects, including potentially life-threatening interactions with certain foods and beverages that contain tyramine, such as aged cheeses, cured meats, and fermented foods.

Individuals taking isocarboxazid should be cautious about their diet and avoid consuming these foods and beverages to prevent serious side effects such as hypertensive crisis. It is essential to talk to your healthcare provider about the risks and benefits of using isocarboxazid and to follow their instructions closely to ensure safe and effective treatment.

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency not defined 

Drowsiness 

Fatigue 

Headache 

Weakness 

Tremor 

Orthostatic hypotension 

Dizziness 

Hyperreflexia 

Sleep disturbance 

Constipation 

Dry mouth 

Anxiety 

Edema 

Irritation 

Hypomania 

Arthralgia 

SIADH 

Jaundice 

Seizure 

Visual disturbance  

Ataxia 

Black Box Warning: 

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

Contraindication/Caution: 

Contraindications: 

• Hypersensitivity to isocarboxazid  
• Concurrent use with other MAO inhibitors, including linezolid, methylene blue, and intravenous methylene blue 
• Pheochromocytoma 
• History of cerebrovascular disease 
• History of liver disease 
• Severe renal impairment 
• Uncontrolled hypertension 
• Cardiovascular disease 
• History of seizures 
• Patients under the age of 16 years 

Cautions: 

• Elderly patients 
• History of mania/hypomania or bipolar disorder 
• Patients with a history of drug abuse or dependence or suicidal thoughts or behaviors 
• Patients with diabetes mellitus 
• Patients with hyperthyroidism 
• Patients with a history of glaucoma 
• Patients with a history of obstructive uropathy or urinary retention  
• Patients with a history of seizures or epilepsy 
• Patients undergoing elective surgery 

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: 

isocarboxazid is a monoamine oxidase inhibitor (MAOI) that works by inhibiting the activity of monoamine oxidase enzymes in the brain, which break down neurotransmitters such as serotonin, norepinephrine, and dopamine. By inhibiting the breakdown of these neurotransmitters, isocarboxazid increases their levels in the brain, which is believed to improve mood and alleviate symptoms of depression. 

isocarboxazid is a non-selective, irreversible MAOI that binds covalently to the enzyme and permanently inactivates it. This effect can last for several weeks after discontinuation of the medication, which is why there is a risk of drug interactions with other medications and dietary restrictions during and after treatment with isocarboxazid. 

Pharmacodynamics: 

The pharmacodynamics of isocarboxazid is primarily related to its mechanism of action as a monoamine oxidase inhibitor (MAOI). By inhibiting the activity of MAO enzymes in the brain, isocarboxazid increases monoamine neurotransmitters such as serotonin, norepinephrine, and dopamine. This increase in neurotransmitter levels is thought to be responsible for the antidepressant effects of isocarboxazid. 

Serotonin, norepinephrine, and dopamine are all involved in regulating mood, emotion, and behavior. Serotonin is associated with feelings of happiness, relaxation, and well-being, while norepinephrine is involved in the body’s response to stress and regulates attention and arousal. Dopamine is associated with pleasure, reward, and motivation. 

By increasing the levels of these neurotransmitters, isocarboxazid can improve mood, alleviate symptoms of depression, and improve motivation and pleasure in daily activities. However, because isocarboxazid is a non-selective and irreversible monoamine oxidase inhibitor, it can also lead to potentially dangerous interactions with other medications and dietary restrictions. 

Individual variations can also influence the pharmacodynamics of isocarboxazid in metabolism and genetic factors. For example, some individuals may have a genetic predisposition to faster or slower metabolism of isocarboxazid, which can affect its efficacy and safety. 

Pharmacokinetics: 

Absorption 

isocarboxazid is well absorbed after oral administration, with peak plasma concentrations occurring approximately 1-2 hours after dosing. 

Distribution 

The absolute bioavailability of isocarboxazid is not well-established, but it is believed to be approximately 50%. 

Metabolism 

isocarboxazid is extensively metabolized in the liver, primarily by the enzyme monoamine oxidase (MAO), which converts the drug to an active metabolite called 2-phenyl propionic acid. This metabolite is responsible for the antidepressant effects of isocarboxazid. 

Elimination and Excretion 

The elimination half-life of isocarboxazid is approximately 2 hours, while that of the active metabolite is approximately 5 hours. isocarboxazid and its metabolites are eliminated mainly in the urine, with a small amount eliminated in the feces. 

Individual differences in metabolism can affect the pharmacokinetics of isocarboxazid. For example, the activity of the MAO enzyme can vary between individuals due to genetic factors, age, and other medications that may induce or inhibit its activity.

Additionally, diet can affect the pharmacokinetics of isocarboxazid since the drug is an irreversible inhibitor of MAO and can lead to a buildup of tyramine and other monoamines in certain foods. Consumption of these foods can lead to a hypertensive crisis in individuals taking isocarboxazid. 

Administration: 

isocarboxazid is typically administered orally as a tablet, usually taken two to three times daily with meals. The dose of isocarboxazid is individualized based on the patient’s age, weight, medical history, and response to treatment. The starting dose is usually 10 mg twice daily, with gradual titration up to a maximum dose of 60 mg daily. It is essential to follow the dosing instructions provided by the healthcare professional. 

isocarboxazid should be taken with food to minimize gastrointestinal side effects. Additionally, because isocarboxazid is an irreversible inhibitor of monoamine oxidase (MAO), it is essential to adhere to dietary restrictions to avoid potentially dangerous interactions with tyramine-containing foods. These restrictions include avoiding aged cheeses, cured meats, fermented or pickled foods, certain types of beer and wine, and other foods high in tyramine. 

isocarboxazid should not be abruptly discontinued, as this can lead to withdrawal symptoms such as headache, anxiety, and depression. Instead, the dose should be gradually tapered under the supervision of a healthcare professional. 

Patient information leaflet 

Generic Name:  isocarboxazid 

Pronounced: iso-carb-oxa-zid 

Why do we use isocarboxazid? 

isocarboxazid is primarily used to treat depression, particularly major depressive disorder (MDD), when other antidepressant treatments have failed or are not well-tolerated. It is a type of medication known as a monoamine oxidase inhibitor (MAOI), which works by increasing the levels of certain neurotransmitters in the brain, such as serotonin, norepinephrine, and dopamine. 

isocarboxazid is particularly useful for treating depression in individuals who have not responded to other antidepressant treatments or experienced intolerable side effects from other medications. It may also be effective for depression with atypical features, such as increased appetite, weight gain, and sleep.