What type of drug is isocarboxazid? A Comprehensive Guide to MAOIs

October 7, 2025 •

3 min read

Isocarboxazid (brand name Marplan), an older antidepressant approved in the U.S. in 1959, is in the class of medications called monoamine oxidase (MAO) inhibitors. It is not considered a first-line treatment for depression due to its complex dietary and drug interactions, but it can be highly effective for those who have not responded to other antidepressants.

Quick Summary

Isocarboxazid is a monoamine oxidase inhibitor (MAOI) prescribed for severe depression, particularly in patients who have not responded to other treatments. Its mechanism involves inhibiting the enzyme monoamine oxidase, leading to increased levels of neurotransmitters like serotonin and norepinephrine. Its use requires strict adherence to dietary and medication precautions to prevent dangerous side effects.

Key Points

Isocarboxazid is a monoamine oxidase inhibitor (MAOI): It belongs to an older class of antidepressants that prevent the breakdown of key neurotransmitters in the brain.
Reserved for severe or treatment-resistant depression: Due to its complex safety profile, isocarboxazid is not a first-line treatment but is used for patients who have not responded to other antidepressants.
Requires strict dietary restrictions: Patients must avoid foods and beverages high in tyramine, as consumption can trigger a dangerous spike in blood pressure known as a hypertensive crisis.
Dangerous drug interactions are a major concern: Isocarboxazid should not be taken with other antidepressants (especially SSRIs), stimulants, or certain over-the-counter drugs due to the risk of severe side effects like serotonin syndrome.
Mechanism involves increasing neurotransmitters: By inhibiting the MAO enzyme, isocarboxazid increases the levels of serotonin, norepinephrine, and dopamine, helping to improve mood.
Available under the brand name Marplan: While often referred to by its generic name, the medication is also known by its brand name, Marplan.
Requires careful medical supervision: Treatment with isocarboxazid necessitates close monitoring by a healthcare professional to manage potential side effects and ensure safety.

Understanding the Mechanism of Isocarboxazid

Isocarboxazid belongs to the class of monoamine oxidase inhibitors (MAOIs). MAO is an enzyme that breaks down neurotransmitters such as serotonin, norepinephrine, and dopamine. By inhibiting MAO, isocarboxazid increases the levels of these neurotransmitters in the brain, helping to improve mood and reduce depressive symptoms. This mechanism makes it particularly useful for treatment-resistant depression or atypical depression when other antidepressants have not been effective. However, the risk of serious interactions limits its use to cases where other treatments have failed.

Therapeutic Uses and Place in Therapy

Isocarboxazid is primarily used to treat major depressive disorder, especially in severe or treatment-resistant cases where other medications have not worked. It is also considered for atypical depression and, in some instances, for panic disorders and social anxieties. Due to potential risks, its prescription requires careful consideration and close medical supervision.

Common Uses of Isocarboxazid

Treatment-resistant depression: For patients unresponsive to multiple other antidepressants.
Atypical depression: Effective for specific symptoms like increased appetite or fatigue.
Anxiety and phobic disorders: May be used for panic disorders and certain social anxieties.

Critical Safety Information: Dietary and Drug Interactions

A critical aspect of taking isocarboxazid is the need to avoid foods high in tyramine, an amino acid. Since isocarboxazid inhibits the breakdown of tyramine, consuming these foods can lead to a dangerous surge in blood pressure called a hypertensive crisis, which can be life-threatening. Symptoms include severe headache and chest pain.

Foods High in Tyramine to Avoid:

Aged cheeses
Cured or fermented meats
Soy products
Certain alcoholic beverages
Yeast extracts
Broad bean pods

Isocarboxazid also interacts with many medications. Combining it with other antidepressants, stimulants, or some pain relievers can cause serious side effects like serotonin syndrome. A period without medication is usually necessary when switching from an MAOI to another antidepressant.

MAOI vs. Newer Antidepressants

To highlight the unique nature of isocarboxazid, consider this comparison with more modern antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).


Feature	Isocarboxazid (MAOI)	Newer Antidepressants (SSRIs/SNRIs)
Drug Class	Monoamine Oxidase Inhibitor	Selective Serotonin Reuptake Inhibitor / Serotonin-Norepinephrine Reuptake Inhibitor
Mechanism of Action	Inhibits the enzyme monoamine oxidase, increasing levels of serotonin, norepinephrine, and dopamine.	Inhibits the reuptake of serotonin (SSRIs) or serotonin and norepinephrine (SNRIs).
Dietary Restrictions	Requires strict avoidance of tyramine-rich foods to prevent hypertensive crisis.	Generally requires no specific dietary restrictions, although some precautions with alcohol may be advised.
Drug Interactions	Numerous potentially serious interactions with other antidepressants, stimulants, and over-the-counter medications.	Fewer serious interactions than MAOIs, but still requires caution, especially with other serotonergic agents.
Typical Use	Reserved for treatment-resistant depression or atypical depression due to significant risks.	Widely used as a first-line treatment for depression, anxiety, and other conditions.
Major Risks	Hypertensive crisis from tyramine, serotonin syndrome from drug interactions.	Lower risk of severe interactions, though serotonin syndrome is still a possibility with other serotonergic drugs.

Conclusion

Isocarboxazid is an MAOI antidepressant used for severe or treatment-resistant depression. Its effectiveness stems from increasing neurotransmitter levels by inhibiting the MAO enzyme. However, its use demands strict adherence to dietary restrictions regarding tyramine and careful management of other medications to avoid dangerous interactions like hypertensive crisis or serotonin syndrome. Close medical supervision is essential for safe and effective treatment with isocarboxazid.

Authoritative Resource for Further Reading

For additional information regarding the safety and proper use of isocarboxazid, the FDA provides the prescribing information and Medication Guide for its brand name, Marplan: accessdata.fda.gov/drugsatfda_docs/label/2007/011961s039lbl.pdf

Disclaimer

This article is for informational purposes only and does not constitute medical advice. Consult with a qualified healthcare professional before making any decisions about your treatment plan. The risks and benefits of taking isocarboxazid must be thoroughly discussed with a doctor, who will determine if it is the right medication for your specific condition. Never start, stop, or change your medication without medical supervision.

Frequently Asked Questions

The primary function of an MAOI like isocarboxazid is to inhibit the monoamine oxidase enzyme, which normally breaks down neurotransmitters. By blocking this enzyme, isocarboxazid increases the levels of serotonin, norepinephrine, and dopamine in the brain, helping to regulate mood.

Isocarboxazid is typically not a first-choice antidepressant due to its significant and potentially dangerous interactions with certain foods and medications. These risks mean it is generally reserved for patients with severe depression who have not responded to safer, newer treatments.

Eating foods rich in tyramine while taking isocarboxazid can cause a hypertensive crisis. This is a severe and rapid increase in blood pressure that can lead to symptoms like a sudden, severe headache, stiff neck, and a fast heartbeat.

Many medications should be avoided, including other MAOIs, SSRIs, SNRIs, certain pain medications (like tramadol), stimulants, and some over-the-counter cold and cough medicines. It is crucial to inform your doctor about all medications and supplements you are taking.

Serotonin syndrome is a potentially life-threatening condition caused by an excess of serotonin in the brain. It can be triggered by combining isocarboxazid with other serotonergic drugs, leading to symptoms like confusion, muscle rigidity, and rapid heart rate.

Dietary restrictions must be continued for at least two weeks after discontinuing isocarboxazid. This is because the drug's enzyme-inhibiting effects can persist in the body for a substantial period after the last dose.

Common side effects include drowsiness, dizziness, dry mouth, constipation, and sexual dysfunction. More serious side effects can occur, and any concerning symptoms should be reported to a healthcare provider immediately.