What does isocarboxazid do? An in-depth pharmacological guide

October 6, 2025 •

3 min read

Isocarboxazid is a monoamine oxidase inhibitor (MAOI) that works by altering the brain's chemical balance to help lift mood. While it is a potent and effective antidepressant, its use requires strict dietary and medication precautions due to potentially dangerous interactions.

Quick Summary

Isocarboxazid treats severe, treatment-resistant depression by inhibiting monoamine oxidase, which increases key neurotransmitter levels in the brain. Its use mandates strict dietary precautions and monitoring for drug interactions.

Key Points

Inhibition of MAO: Isocarboxazid belongs to the MAOI class, which blocks the monoamine oxidase enzyme responsible for breaking down key neurotransmitters.
Increased Neurotransmitter Levels: By inhibiting MAO, the medication increases brain levels of serotonin, norepinephrine, and dopamine to improve mood and emotional balance.
Treatment-Resistant Depression: It is typically used for severe depression, especially when other antidepressants, like SSRIs, have been ineffective.
Critical Dietary Restrictions: Patients must avoid foods and beverages high in tyramine (aged cheese, fermented meats, certain alcohols) to prevent a dangerous hypertensive crisis.
Significant Drug Interactions: Combining isocarboxazid with other antidepressants, stimulants, and certain pain medications is extremely dangerous and can cause severe reactions like serotonin syndrome.
Serious Side Effects: Potential adverse effects include hypertensive crisis, suicidal ideation, and hepatotoxicity, necessitating close medical supervision.

What does isocarboxazid do in the brain?

Isocarboxazid, marketed as Marplan®, is a monoamine oxidase inhibitor (MAOI). It functions by irreversibly blocking the monoamine oxidase (MAO) enzyme, which normally metabolizes monoamine neurotransmitters like serotonin, norepinephrine, and dopamine. By inhibiting MAO, isocarboxazid raises the levels of these neurotransmitters in the brain, which helps to alleviate depressive symptoms.

The mechanism of action: Blocking the MAO enzyme

MAO is present throughout the body in two forms, MAO-A and MAO-B. Isocarboxazid inhibits both types, impacting a wider range of neurotransmitters than some newer antidepressants. The resulting increase in serotonin, norepinephrine, and dopamine contributes to improved mood, alertness, and motivation.

Therapeutic applications: Who benefits from isocarboxazid?

Isocarboxazid is not typically the initial treatment for depression due to its potential side effects and interactions. It is primarily used for severe depression, especially in patients who have not responded to other antidepressants like SSRIs. It can be particularly effective for atypical depression, characterized by mood reactivity, increased appetite, and excessive sleep. It may also help with panic disorders and social anxiety.

Critical dietary and drug interactions

A critical consideration when using isocarboxazid is the need for strict dietary and medication precautions.

The tyramine effect

Isocarboxazid's inhibition of MAO prevents the breakdown of tyramine, a compound found in many aged and fermented foods. A buildup of tyramine can lead to a hypertensive crisis, a dangerous surge in blood pressure. Foods to avoid include aged cheeses, cured meats, fermented foods, certain alcoholic beverages, and excessive caffeine.

Dangerous drug combinations

Isocarboxazid interacts with numerous medications. Combining it with other antidepressants like SSRIs can cause serotonin syndrome, a potentially fatal condition. Stimulants and certain pain medications, such as meperidine and tramadol, should also be avoided due to the risk of hypertensive crisis or other severe reactions. St. John's Wort should not be used with isocarboxazid.

Side effects and monitoring

Side effects can vary, and close medical monitoring is necessary.

Common side effects

Common side effects include dry mouth, dizziness, constipation or diarrhea, changes in sleep patterns, and sexual dysfunction.

Serious adverse events

Serious risks include hypertensive crisis, serotonin syndrome, increased suicidal thoughts (especially in young adults), and rare liver injury. Symptoms of hypertensive crisis or serotonin syndrome require immediate medical attention.

Isocarboxazid vs. other antidepressants


Feature	Isocarboxazid (MAOI)	Sertraline (SSRI)
Drug Class	Monoamine Oxidase Inhibitor	Selective Serotonin Reuptake Inhibitor
Mechanism	Non-selectively inhibits MAO, increasing serotonin, norepinephrine, and dopamine.	Selectively inhibits serotonin reuptake, increasing serotonin.
Dietary Restrictions	Strict avoidance of tyramine-rich foods and beverages required.	None typically required.
Drug Interactions	Numerous and severe interactions with other antidepressants, stimulants, and certain pain meds.	Potential interactions, but generally safer profile than MAOIs.
First-line Treatment	No; reserved for treatment-resistant depression.	Yes; often a first-line option.
Onset of Action	Can be slow, taking weeks to reach full effect.	Can also be slow, often 4-6 weeks for full therapeutic effect.
Common Side Effects	Dizziness, dry mouth, sexual dysfunction, insomnia.	Nausea, headache, sexual dysfunction, insomnia.
Serious Side Effects	Hypertensive crisis, serotonin syndrome, hepatotoxicity.	Serotonin syndrome (rare), increased bleeding risk, suicidal thoughts (boxed warning).

Conclusion

Isocarboxazid is a potent MAOI antidepressant used for severe, treatment-resistant depression. It increases neurotransmitter levels by inhibiting the MAO enzyme. However, its use requires strict dietary and medication precautions due to the risk of serious interactions like hypertensive crisis and serotonin syndrome. While not a first-line treatment, it can be beneficial for patients who haven't responded to other therapies. The risks and benefits must be carefully evaluated, and close medical supervision is essential.

Disclaimer: This article is for informational purposes only and is not a substitute for professional medical advice. Always consult a qualified healthcare provider for any medical concerns or before starting or changing any treatment.

Frequently Asked Questions

The brand name for isocarboxazid is Marplan®, which is available as an oral tablet.

Strict dietary restrictions are necessary because isocarboxazid blocks the enzyme that breaks down tyramine. Consuming tyramine-rich foods can lead to a severe and potentially fatal spike in blood pressure, known as a hypertensive crisis.

You should avoid aged cheeses, cured meats, fermented products, certain alcoholic beverages like red wine and beer, and foods with excessive caffeine. It is critical to get a detailed list from your healthcare provider.

No, combining isocarboxazid with SSRIs or other antidepressants is extremely dangerous and can lead to serotonin syndrome, a life-threatening condition caused by too much serotonin.

Serotonin syndrome is a serious and potentially fatal condition resulting from an excess of serotonin. Symptoms can include high fever, muscle rigidity, confusion, and agitation.

Common side effects include dizziness, dry mouth, constipation, insomnia or drowsiness, and decreased sexual ability.

No, it is not a first-line treatment. Due to its potential for severe side effects and interactions, it is usually reserved for patients with severe or treatment-resistant depression who have not responded to other medications.