What Does Isocarboxazid Treat? An MAOI for Severe Depression

October 8, 2025 •

4 min read

Over 20 million adults experience major depressive episodes annually in the U.S.. For those who haven't found relief with common medications, what does isocarboxazid treat? Isocarboxazid is a potent monoamine oxidase inhibitor (MAOI) reserved for treatment-resistant depression and specific anxiety disorders.

Quick Summary

Isocarboxazid is a powerful MAOI antidepressant used for severe, treatment-resistant depression, atypical depression, and certain anxiety and panic disorders after other medications have failed.

Key Points

For Treatment-Resistant Depression: Isocarboxazid is primarily used when other standard antidepressants, like SSRIs or SNRIs, have failed to provide relief.
Targets Atypical Depression: It is particularly effective for depression with atypical features, such as increased appetite, oversleeping, and mood reactivity.
Treats Co-Occurring Anxiety: The medication can also be prescribed to address co-occurring anxiety disorders, panic disorder, and social phobia.
Requires Strict Dietary Adherence: Patients must follow a low-tyramine diet to avoid a life-threatening hypertensive crisis.
Dangerous Drug Interactions Exist: Isocarboxazid interacts negatively with numerous medications, necessitating careful avoidance of other antidepressants, decongestants, and some pain relievers.
MAOI Mechanism of Action: As an MAOI, it increases the levels of mood-regulating neurotransmitters like serotonin and norepinephrine by inhibiting their breakdown.
Reserved for Specialized Use: Due to its safety profile and complex management, it is not a first-line medication but a specialized option for specific patient populations.

What is Isocarboxazid?

Isocarboxazid, sold under the brand name Marplan, is a type of antidepressant belonging to a class of drugs known as monoamine oxidase inhibitors (MAOIs). As one of the earliest antidepressants developed in the 1950s, it works by targeting the monoamine oxidase enzyme in the brain. Due to its significant side effect profile and extensive food and drug interactions, it is not a first-line treatment. Instead, it is reserved for patients whose depression has not responded to other, newer antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

How Isocarboxazid Works

To understand what isocarboxazid treats, it is important to know its mechanism of action. The monoamine oxidase enzyme naturally breaks down monoamine neurotransmitters, which include serotonin, norepinephrine, and dopamine. Low levels of these neurotransmitters are thought to play a role in depression. Isocarboxazid inhibits this enzyme, preventing the breakdown of these crucial mood-regulating chemicals. By doing so, it increases the concentration of these neurotransmitters in the brain, which helps to alleviate depressive symptoms. This action can help restore mental balance in some individuals.

Primary Indications for Isocarboxazid

Isocarboxazid is primarily used to treat severe depression that is resistant to other forms of therapy. Specific types of depression for which it may be particularly effective include:

Treatment-Resistant Depression (TRD): For individuals who have tried multiple courses of other antidepressants without success, isocarboxazid offers an alternative pathway to address their symptoms.
Atypical Depression: This subtype of depression often features mood reactivity (mood temporarily brightens in response to positive events), weight gain, hypersomnia (oversleeping), and a feeling of heaviness in the limbs known as "leaden paralysis". MAOIs are sometimes favored for treating these specific features.

Additional Approved and Off-Label Uses

Beyond its primary use for depression, isocarboxazid can also be effective for a range of other conditions when prescribed by a healthcare provider, sometimes in an off-label capacity. These include:

Anxiety and Panic Disorders: Isocarboxazid can be used to treat certain anxiety disorders and panic attacks. Its mechanism of action can help regulate the neurochemical imbalances contributing to these conditions.
Social Phobia: In some cases, isocarboxazid has been shown to reduce excessive nervousness in individuals with social anxiety disorder.
Historical and Investigational Uses: Historically, MAOIs were investigated for other neurological conditions. Some sources mention investigation in the treatment of schizophrenia, Parkinson's disease, and other dementia-related disorders. However, newer, more targeted treatments are now standard for these conditions.

Crucial Dietary and Drug Interactions

One of the main reasons isocarboxazid is not a first-line treatment is its potential for dangerous interactions with certain foods and other medications. These interactions can lead to a severe and potentially life-threatening condition known as a hypertensive crisis, characterized by a sudden, dangerous spike in blood pressure.

Foods to avoid when taking Isocarboxazid

Aged and Fermented Foods: Cheeses (especially aged ones like cheddar, blue, and Swiss), sour cream, and yogurt.
Cured and Processed Meats: Salami, pepperoni, pickled herring, anchovies, and liver.
Alcoholic Beverages: Chianti wine, sherry, liqueurs, and all beer, including non-alcoholic versions.
Other High-Tyramine Foods: Soy sauce, sauerkraut, fava beans, and yeast extracts.
Excessive Caffeine: Large quantities of caffeine can also pose a risk and should be avoided.

Medications to avoid when taking Isocarboxazid

Combining isocarboxazid with certain medications can lead to dangerous side effects, including serotonin syndrome, a life-threatening condition caused by an excess of serotonin. A comprehensive list of contraindicated medications includes:

Other MAOIs: Must not be used within 14 days of each other.
SSRIs and SNRIs: A waiting period of several weeks is required when switching between these drugs and an MAOI.
Tricyclic Antidepressants (TCAs).
Opioid Pain Medications: Such as meperidine and tramadol.
Certain ADHD Medications: Amphetamines and methylphenidate.
Over-the-Counter Drugs: Including decongestants and cough medicines containing dextromethorphan.
Sympathomimetics.
St. John's Wort: An herbal supplement.

Isocarboxazid vs. Modern Antidepressants

To highlight why isocarboxazid is a reserved option, the following table compares MAOIs with more commonly prescribed SSRIs/SNRIs.


Feature	Isocarboxazid (MAOI)	SSRIs/SNRIs
Mechanism of Action	Inhibits the enzyme monoamine oxidase, increasing levels of multiple neurotransmitters (serotonin, norepinephrine, dopamine).	Selectively inhibits the reuptake of serotonin (SSRIs) or both serotonin and norepinephrine (SNRIs).
Efficacy	Often highly effective for treatment-resistant and atypical depression, sometimes superior to newer drugs for specific patients.	Effective for a wide range of depressive and anxiety disorders, and generally well-tolerated by most patients.
First-Line Status	Not a first-line treatment due to safety concerns and dietary restrictions.	Often considered a first-line treatment for depression.
Dietary Restrictions	Requires a strict low-tyramine diet to prevent hypertensive crisis.	No dietary restrictions are required.
Drug Interactions	Extensive, potentially life-threatening interactions with many common medications.	Fewer serious drug interactions compared to MAOIs, but still require caution with other serotonergic agents.
Side Effects	Can include dizziness, insomnia, dry mouth, and weight gain. Has a risk of rare but serious reactions like hypertensive crisis and serotonin syndrome.	May include nausea, dizziness, sexual dysfunction, and agitation, but generally milder and more manageable.

Conclusion

Isocarboxazid is a powerful monoamine oxidase inhibitor (MAOI) that serves as a critical treatment option for individuals with severe, treatment-resistant, or atypical depression who have not responded to other antidepressants. While effective, its use requires careful management and strict adherence to dietary restrictions and medication interaction guidelines to prevent serious adverse effects like hypertensive crisis. For some patients, navigating these complexities is worth the potential for significant symptom relief when other options have failed. The decision to use isocarboxazid should always be made in close consultation with a healthcare professional, with careful monitoring and patient education.

Frequently Asked Questions

The primary purpose of isocarboxazid is to treat severe depression, especially in cases where other antidepressant medications have been ineffective. It is also used for specific anxiety and panic disorders.

Isocarboxazid is not a first-choice antidepressant because it belongs to a class of drugs (MAOIs) with potentially dangerous food and drug interactions. It requires strict dietary restrictions and careful medication management to avoid serious side effects.

Patients must avoid foods high in tyramine, which can cause a hypertensive crisis. This includes aged cheeses, cured meats, fermented products like soy sauce and sauerkraut, and some types of alcohol.

Isocarboxazid works by inhibiting the monoamine oxidase enzyme, which normally breaks down neurotransmitters like serotonin, norepinephrine, and dopamine. By blocking this enzyme, isocarboxazid increases the levels of these mood-regulating chemicals in the brain.

No, you should not take other antidepressants, including SSRIs, SNRIs, and TCAs, with isocarboxazid. Doing so can lead to dangerous side effects like serotonin syndrome. There are specific waiting periods required when switching between these medications.

Common side effects include drowsiness, dizziness, insomnia, dry mouth, constipation, and decreased sexual ability. Less common but more severe side effects, like a hypertensive crisis, can occur with improper use.

Yes, aside from its use for treatment-resistant and atypical depression, isocarboxazid is also prescribed for anxiety disorders, panic disorder, and social phobia.