Isocarboxazid (Marplan)

What it treats

Isocarboxazid is approved by the U.S. Food and Drug Administration to treat depression, particularly depression that hasn't responded to other treatments.

Off-label use for anxiety disorders happens but is uncommon. Off-label means a purpose the label doesn't formally list even though evidence and practice support it.

How it works

Isocarboxazid blocks monoamine oxidase, or MAO, the enzyme that breaks down serotonin, norepinephrine, and dopamine (and dietary tyramine). Blocking it raises levels of these messengers in the brain.

Its block is irreversible: it permanently disables the MAO molecules it binds. New MAO takes about two weeks to regenerate, which is why diet and drug restrictions have to hold for two weeks after the last dose.

Receptor mechanism (detail)

Isocarboxazid is an irreversible, non-selective inhibitor of MAO-A and MAO-B. Its clinical profile is broadly similar to phenelzine. Because it blocks MAO-A in the gut, dietary tyramine restrictions apply. Because it blocks serotonin metabolism, other serotonergic drugs risk serotonin syndrome.

Potency and typical dosing pattern

Ranges are typical framework only, not a prescription for any individual.

Starting is 10 mg twice a day. Titration goes to 40 to 60 mg per day divided.

Safety monitoring

• Blood pressure at every visit. Both hypertensive crisis and orthostatic hypotension are on the table.
• Tyramine-restricted diet. Avoid aged cheeses, cured or aged meats, tap or unpasteurized beer, sauerkraut, kimchi, soy sauce and other fermented soy products, fava beans, and overripe or spoiled foods.
• 14-day washout before starting most other antidepressants and 14 days after stopping isocarboxazid before starting them. For fluoxetine specifically, wait 5 weeks after stopping it before starting isocarboxazid.
• Avoid serotonergic drugs during and for 14 days after: SSRIs, SNRIs, tramadol, meperidine, dextromethorphan, triptans, linezolid, methylene blue, St. John's wort, MDMA.
• Suicidality in the first 4 weeks, especially under age 25 (FDA boxed warning).
• Liver function occasionally checked given rare hepatotoxicity reports.

What to expect

Common side effects

Common side effects include:

• Dizziness on standing.
• Dry mouth.
• Constipation.
• Sleep disturbance.
• Sexual side effects.
• Weight gain.
• Edema.

If a side effect is severe, or it isn't improving, that's a conversation to have with the prescriber rather than a reason to stop on your own.

Serious side effects and warnings

Serious problems are uncommon, but a few really matter.

Boxed warning. Like all antidepressants, isocarboxazid carries an FDA boxed warning that it can increase suicidal thoughts and behaviors in children, teenagers, and young adults under 25, especially in the first weeks of treatment or after a dose change.

• Hypertensive crisis. Tyramine-rich foods or sympathomimetic drugs (some cold medicines, ephedra, some ADHD stimulants, cocaine, amphetamine) can drive blood pressure to dangerous levels. Severe pounding headache, chest pain, nausea and vomiting, sweating, and racing heart are warning signs. Medical emergency.
• Serotonin syndrome. Combining isocarboxazid with other serotonergic drugs can cause severe agitation, fever, muscle rigidity, and altered mental status. Also a medical emergency.
• Orthostatic hypotension.
• Liver injury. Rare but reported; liver function is worth watching.

Sexual side effects

Sexual side effects (reduced desire, delayed orgasm, erectile difficulty) are common, at rates similar to phenelzine. If they appear, they're worth raising with the prescriber.

Weight, appetite, and sleep

Isocarboxazid can cause weight gain, though usually less than phenelzine. Sleep effects are variable.

Starting and dosing basics

This section is general background, not a dosing instruction for any individual. The right dose is a decision for a prescriber.

Isocarboxazid comes as tablets. Starting is at 10 mg twice a day, with steps up over days to weeks. A prescriber comfortable with MAOIs will walk through the diet and drug rules in detail before the first dose.

Missed doses and interactions

If you miss a dose, take it when you remember, unless it's almost time for the next dose. Skip the missed dose and carry on. Don't take two doses to make up for one.

Interactions are extensive. Common categories:

• Do not combine with SSRIs, SNRIs, other MAOIs, tramadol, meperidine, dextromethorphan, triptans, linezolid, methylene blue, St. John's wort, MDMA, or amphetamines.
• Use with caution with sympathomimetic decongestants, tyramine-rich foods, and any drug that raises blood pressure.
• Wait 14 days after stopping isocarboxazid before starting a serotonergic drug (5 weeks after fluoxetine before starting isocarboxazid).

Give every prescriber and pharmacist a full list of your medications and supplements, including over-the-counter ones. Carry a card that says you take an MAOI.

Stopping and tapering

Isocarboxazid isn't a controlled substance and isn't habit-forming in the usual sense.

The body does adjust to it, though, and stopping abruptly can cause discontinuation symptoms. The 14-day period after stopping is also when tyramine restrictions and drug interactions still hold. A prescriber typically tapers rather than stopping suddenly.

Pregnancy and breastfeeding

This is an area where individual circumstances matter and the decision belongs with a clinician. Data in pregnancy are limited, and MAOIs are generally avoided when alternatives exist. Anyone who is pregnant, planning a pregnancy, or breastfeeding should talk it through with their prescriber so the specific risks and benefits can be weighed for their situation.

Cost and generic availability

Isocarboxazid isn't widely stocked because it isn't commonly prescribed. Availability and cost vary; a pharmacy may need time to source it.

Common questions

How is isocarboxazid different from phenelzine and tranylcypromine? All three are irreversible non-selective MAOIs with the same diet and drug rules. Clinically they're similar. Isocarboxazid is the least prescribed of the three in the U.S., largely for historical reasons and reduced familiarity.

Do I still need the tyramine diet? Yes. Non-selective MAO-A inhibition is what forces the diet.

Do MAOIs still work when SSRIs haven't? Yes, often. That's the niche for isocarboxazid today.

Why 14 days between MAOIs and other antidepressants? Isocarboxazid irreversibly inactivates MAO. New enzyme takes about two weeks. During that window, combining serotonergic drugs can cause serotonin syndrome.

Is it addictive? No. It's not a controlled substance and doesn't cause cravings. Stopping should still be planned with a prescriber.

Questions to ask your prescriber

• Is my prescriber comfortable with MAOIs, or should we consider a referral?
• Can we go through the tyramine diet together, and can I get a printed list?
• Which medications and supplements do I need to avoid?
• What warning signs should send me to the emergency room?
• If we decide to stop it later, how would we do that safely, and how long do the diet rules hold after stopping?

Sources

This guide draws on current prescribing information and public health references and current as of June 8, 2026. It is reviewed for clinical accuracy and updated as guidance changes.

• U.S. Food and Drug Administration. Isocarboxazid (Marplan) prescribing information.
• MedlinePlus, U.S. National Library of Medicine. Isocarboxazid.
• National Institute of Mental Health. Mental health medications.
• American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder.
• National Institute for Health and Care Excellence (NICE). NG222, Depression in adults.