Understanding the Medication Classification of Isocarboxazid

October 12, 2025 •

2 min read

Isocarboxazid, an older antidepressant approved in the US in 1959, belongs to a medication classification known as monoamine oxidase inhibitors (MAOIs). While its use has declined due to newer antidepressants with fewer side effects, it remains a valuable option for certain cases of severe depression resistant to other treatments.

Quick Summary

Isocarboxazid is classified as a non-selective, irreversible monoamine oxidase inhibitor (MAOI), a class of medications that block the MAO enzyme to increase neurotransmitter levels. It is used for severe depression but requires strict dietary and medication precautions due to serious interaction risks.

Key Points

Monoamine Oxidase Inhibitor (MAOI): Isocarboxazid is primarily classified as an MAOI, a class of antidepressant drugs that inhibit the monoamine oxidase enzyme.
Non-Selective Inhibition: It blocks both MAO-A and MAO-B enzymes, which affect the metabolism of several neurotransmitters and tyramine, a compound found in many foods.
Irreversible Action: Isocarboxazid permanently deactivates the MAO enzyme, requiring the body to synthesize new enzymes to restore normal function.
High-Risk Interactions: Taking isocarboxazid requires avoiding tyramine-rich foods and many medications due to the risk of hypertensive crisis or serotonin syndrome.
Last-Resort Treatment: Due to its side effects and interaction risks, isocarboxazid is typically reserved for severe depression that has not responded to other treatments.
Extensive Precautions: Patients must be closely monitored and educated on necessary dietary changes and contraindicated medications to ensure safe use.

The Monoamine Oxidase Inhibitor (MAOI) Class

Isocarboxazid is classified as a monoamine oxidase inhibitor (MAOI), a historical class of antidepressant drugs. MAOIs work by inhibiting the monoamine oxidase enzyme, which helps regulate neurotransmitters in the brain. Unlike newer antidepressants, MAOIs have a broader effect and require careful monitoring due to potential side effects and interactions with certain foods and other medications.

Isocarboxazid's Specific Mechanism and Subclass

Isocarboxazid is a non-selective, irreversible MAOI of the hydrazine chemical class.

Non-selective: It inhibits both MAO-A and MAO-B enzymes, which affects various neurotransmitters and tyramine. This non-selective action contributes to its effects and the need for strict dietary restrictions to avoid hypertensive crisis from tyramine buildup.
Irreversible: Isocarboxazid permanently binds to and deactivates the MAO enzyme, meaning the body needs to create new enzymes for normal function. This process can take up to two weeks or more after stopping the medication.
Hydrazine Class: Chemically, it's a hydrazine compound, differing from other MAOIs like tranylcypromine.

Clinical Use, Precautions, and Contraindications

Isocarboxazid (Marplan) is used for major depressive disorder, especially when other antidepressants haven't been effective. It's not a first-line treatment due to its risks and necessary precautions.

Critical precautions and side effects

Dietary Restrictions: A strict low-tyramine diet is essential. Tyramine in aged or fermented foods can cause a dangerous hypertensive crisis.
Serious Drug Interactions: Combining isocarboxazid with many medications can lead to severe conditions like serotonin syndrome or hypertensive crisis. Contraindicated drugs include SSRIs, other MAOIs, TCAs, sympathomimetics, certain pain medications (like meperidine), dextromethorphan, stimulants, and diet pills.
Contraindications: Certain conditions preclude its use, such as cardiovascular disease, hypertension, liver or kidney disease, pheochromocytoma, and a history of headaches or stroke.

Comparison of MAOIs

The table below outlines key differences between isocarboxazid and other common MAOIs.


Feature	Isocarboxazid (Marplan)	Phenelzine (Nardil)	Tranylcypromine (Parnate)	Moclobemide (reversible MAOI)
Selectivity	Non-selective	Non-selective	Non-selective	Reversible, selective for MAO-A
Reversibility	Irreversible	Irreversible	Irreversible	Reversible
Chemical Class	Hydrazine	Hydrazine	Non-hydrazine	Non-hydrazine
Action	Inhibits MAO	Inhibits MAO	Inhibits MAO with stimulating effect	Reversibly inhibits MAO-A
Dietary Restriction	Strict restrictions required	Strict restrictions required	Strict restrictions required	Less strict restrictions

Side Effects and Patient Considerations

Common side effects of isocarboxazid can include dizziness, orthostatic hypotension, drowsiness, insomnia, dry mouth, constipation, diarrhea, weight gain, and sexual dysfunction. Patient education on dietary and drug interactions is crucial, including recognizing symptoms of a hypertensive crisis. Close medical supervision is needed throughout treatment. While its complex risk profile has led to it being less used than newer antidepressants, isocarboxazid can be beneficial for certain patients under careful medical guidance.

Conclusion

Isocarboxazid is classified as a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class. It's used for severe depression but requires significant precautions due to the risk of serious interactions with certain foods and medications, such as hypertensive crisis or serotonin syndrome. Strict adherence to dietary restrictions and avoiding contraindicated drugs is essential for safe use. Further information is available on the FDA website.

Frequently Asked Questions

The primary medication class of isocarboxazid is a monoamine oxidase inhibitor (MAOI).

Strict dietary restrictions are necessary to avoid foods high in tyramine, which can cause a potentially life-threatening hypertensive crisis when the MAO enzyme is inhibited.

Isocarboxazid works by blocking the monoamine oxidase enzyme, which prevents the breakdown of neurotransmitters like serotonin and norepinephrine, increasing their levels in the brain.

Serious side effects can include hypertensive crisis, serotonin syndrome, severe headaches, chest pain, and significant fluctuations in vital signs.

No, isocarboxazid is not a first-line treatment. It is usually reserved for patients with severe depression who have not responded to more modern antidepressants due to its significant side effects and interactions.

Due to its irreversible action, the effects of isocarboxazid can last for at least 10 to 14 days after discontinuation while the body produces new MAO enzymes.

Combining isocarboxazid with other antidepressants, especially SSRIs, can cause a dangerous drug interaction known as serotonin syndrome.