Isocarboxazid (Marplan)

Isocarboxazid is a mono amine oxidase inhibitor antidepressant. It was introduced by Hoffman-LaRoche Pharmaceuticals in 1959. They stopped manufacturing Marplan in 1994, but resumed compassionate distribution (limited distribution to people who could not switch to other medications) shortly afterward. Oxford Pharmaceuticals purchased distribution rights in 1998 and they continue to supply Marplan in the US.

The Bottom Line: What You Really Need to Know

Uses of isocarboxazid

In the US, isocarboxazid is approved for the treatment of depression and panic disorder. In the United Kingdom, it is only approved to treat depression that does not respond to SSRI antidepressants. It may also be useful in treating bulimia.

Isocarboxazid is not usually used as a "first line" drug in treating depression; it is reserved for people who do not respond to other drugs.

Dosage and instructions

You have to gradually increase the dose of isocarboxazid when you start taking it. You usually start with 10 mg twice a day and increase your dose by 10 mg/day every 2-4 days as directed by your doctor until you are taking a total of 40 mg/day. At that point, your doctor may have you take 20 mg twice a day or 10 mg 4 times a day.

The maximum recommended dose of isocarboxazid is 60 mg daily; however, amounts over 40 mg/day should be used with caution.

It takes 3-6 weeks for isocarboxazid to take effect.

How isocarboxazid works

Isocarboxazid inhibits the action of a complex enzyme system known as mono amine oxidase. It works in the brain, heart and liver. How MOA inhibition helps depression is not clearly understood.

Side effects

One of the reasons isocarboxazid is rarely used, especially as a first line drug, is that it has so many possible side effects. (The other reason is that it interacts with many medications and foods.) The most common side effects are nausea, constipation or diarrhea, dry mouth and dizziness.

Some of the other side effects that can occur with isocarboxazid are:

Interactions

Isocarboxazid interacts with many medications, including:

Isocarboxazide interacts with many foods, too, especially foods that have been aged. Some foods that interact are:

You can download a pocket food guide at http://validuspharma.com/dev/MarplanDietCard.pdf.

Withdrawal

When you stop taking isocarboxazid, it must be tapered to prevent withdrawal symptoms. The dose is usually decreased by 10 mg every 2-4 days until you are taking 20 mg/day, then it can be stopped. If you experience withdrawal symptoms, however, more gradual tapering is needed. Symptoms of isocarboxazid withdrawal are restlessness, anxiety, worsening depression, confusion, hallucinations, headache, weakness and diarrhea.

Warnings, precautions and contraindications

Contraindications: You should not take isocarboxazid if you have a history of cerebrovascular or cardiovascular disease, hypertension, pheochromocytoma, liver disease, kidney disease or chronic headaches.

Serious and sometimes fatal reactions can occur between isocarboxazid and SSRI medications. At least two weeks should elapse between stopping one medication and starting the other.

Hypertensive crisis: Hypertensive crisis can occur when you take isocarboxazid, especially if you are taking incompatible medications or foods. In hypertensive crisis, your blood pressure gets very high very quickly. Symptoms of hypertensive crisis can include severe headache, neck pain and stiffness, chest pain and sweating. Heart attack, stroke or death can occur.

You should monitor your blood pressure while you are taking isocarboxazide and notify your doctor immediately if it is higher than usual or if you experience headache, chest pain or other symptoms.

Hypotension: Isocarboxazid can also cause low blood pressure (hypotension). This is most likely to occur when you stand up suddenly and "all the blood rushes to your feet." You feel faint or dizzy and may pass out.

Until you know how your body reacts to isocarboxazid you should stand up slowly to give your body time to adjust.

Hepatotoxicity: Isocarboxazid can cause damage to your liver or make pre-existing damage worse. Your doctor will probably order liver function tests periodically. Notify your doctor if you notice yellowing of your eyes or skin.

Seizures: Isocarboxazid increases the frequency of seizures in some people.

Suicidal tendencies: There is an increased risk of suicide in the first few weeks of therapy with any antidepressant. You will have frequent appointments with your physician or a therapist for the first month or two. A friend or family member will need to check on you every day and ask how you are doing. The physician should be notified if you are having thoughts of harming yourself or others, deepening depression, agitation and restlessness, unusual thoughts or other symptoms.

Activation of mania: Depressed people sometimes also experience anxiety and agitation; isocarboxazid can increase those feelings. That is also true with schizophrenic people. Isocarboxazid can trigger a manic episode in people who have bipolar disease and can cause rapid cycling between depression and mania.

Pregnancy: In one small study, there was evidence that isocarboxazid is associated with birth defects when taken during the first trimester of pregnancy.

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