Isocarboxazid
Isocarboxazid
Purpose
Isocarboxazid (brand name Marplan) is an older-generation antidepressant drug. It is used to treat symptoms associated with major depressive disorder. Major depressive disorder refers to a long-lasting bout of depressed mood that is severe enough to interfere with basic life activities like work, relationships, sleeping, and eating. Feelings of self-worth, interest, motivation, and pleasure are typically absent while worthlessness, emptiness, being overwhelmed, and sadness are often reported.
Isocarboxazid is used for long-term maintenance of major depression and may be most useful for patients whose depression has atypical features. Unless effectiveness has already been established for a particular patient, isocarboxazid would not be the first drug of choice. Its use is limited to those patients who do not respond to first-line antidepressants and who are amenable to close supervision. Isocarboxazid’s status as a drug of last resort (as is the case with other drugs in its class) is due to its potentially dangerous side effects and the dietary restrictions taking it requires.
The safety of isocarboxazid in children has not been established.
Description
Isocarboxazid belongs to the class of antidepressants known as monoamine oxidase inhibitors (MAOIs). The MAOIs inhibit the function of an enzyme in the body called monoamine oxidase; that enzyme breaks down monoamine neurotransmitters—namely serotonin, dopamine , and norepinephrine. Under normal conditions, monoamine oxidase halts the action of these neurotransmitters. With MAOIs, the neurotransmitters last longer and accumulate, and their action is enhanced. It is this enhancement of neurotransmitter action that is thought to contribute to isocarboxazid’s therapeutic efficacy.
There are two types of monoamine oxidases; they are denoted MAO-A and MAO-B. Isocarboxazid acts on both types, as do other nonselective monoamine oxidase inhibitors such as phenelzine and tranylcypormine.
Monoamine oxidase inhibitors do not elevate mood in non-depressed people. In depressed patients, they are used when other, first-line antidepressants are ineffective.
Recommended dosage
Isocarboxazid is taken orally. As is the case with most antidepressant drugs, patients are started at one dose and medication is gradually increased to a so-called maintenance dose to achieve the best outcome. For isocarboxazid, the starting dose is 10 mg, twice a day. Whereas dosage can vary widely in individual patients, a typical progression would be to increase the dose gradually to 15-30 mg twice a day as a maintenance dose. Because of the delayed therapeutic response, at least one to two weeks should pass before increasing the dose.
Precautions
Patients taking isocarboxzaid must be warned about food interactions. Foods like aged cheese, beer, and red wine contain tyramine and in concert with MAOIs can result in hypertensive crisis. Other foods high in tyramine (or dopamine itself) are bananas, fava beans, figs, raisins, yogurt, sour cream, soy sauce, pickled herring, caviar, liver, and tenderized meats; these foods should not be consumed when taking isocarboxazid.
Hypertensive crisis can also occur with certain drug interactions (detailed below). Monoamine oxidase inhibitors should not be taken with asthma drugs, cold and allergy medications, or diet drugs. Patients taking isocarboxazid should inform their doctors and dentists of that fact to avoid being administered a contraindicated medication.
Isocarboxazid use may negatively interact with certain health conditions. It should not be used in patients with cardiovascaular disease, cerebrovascular disease, or liver disease, and great caution should be used if there is poor kidney function or a history of seizures.
KEY TERMS
Antidepressant —A medication taken to alleviate clinical depression.
Major depressive disorder —A clinical psychiatric diagnosis of chronic depressed mood that interferes with normal life activities.
Dopamine —A chemical messenger in the brain that regulates reward and movement.
Hypertensive crisis —A precipitous rise in high blood pressure that can lead to brain hemorrhage or heart failure.
Monoamine oxidase inhibitors (MAOIs) —A class of antidepressant drugs that work by enhancing the neurotransmitters dopamine, norepinephrine, and serotonin in the brain.
Neurotransmitters —Chemical messengers that transmit signals between nerves.
Norepinephrine —A chemical messenger in the brain that regulates arousal and attention.
Serotonin —A chemical messenger in the brain that regulates arousal and mood.
Worsening of depression and risk of suicide are relevant to isocarboxazid, as they are to all antidepressant drugs. The risk is especially high during the lag time until therapeutic efficacy can be achieved. Close monitoring of patients for the first four weeks of treatment is advised.
Side effects
Isocarboxazid, like the other MAOIs, can cause a variety of side effects apart from the food interactions described above. Common side effects include dizziness and fainting associated with low blood pressure when standing up (orthostatic hypotension), sexual dysfunction, anxiety , headache, nausea, sleep disturbances, edema, constipation, and weight gain. Serious but less common side effects include hepatic damage.
Interactions
A patient should not take isocarboxazid at the same time as other antidepressants. Two to five weeks of wash-out time must pass before switching from a non-MAOI antidepressant drug to isocarboxazid.
The following drugs should not be taken with MAOIs: Stimulants like amphetamine, methylphenidate , and epinephrine; dopaminergic drugs like levodopan, L-tryptophan, and phenylalanine;over-the-counter cold and allergy medications like pseudoephedrine and dextromethorphan; diet drugs like ephedrine and phenylpropanolamine; and analgesics like meperidine.
Resources
BOOKS
Charney, Dennis S., MD, and Charles B. Nemeroff, MD, PhD. The Peace of Mind Prescription: An Authoritative Guide to Finding the Most Effective Treatment for Anxiety and Depression. New York: Houghton Mifflin, 2004.
Morrison, Andrew L., MD, The Antidepressant Sourcebook:A User’s Guide for Patients and Families. New York: Doubleday, 1999.
Beers, Mark H., ed. “Depressive Disorders.” The Merck Manual of Diagnosis and Therapy, Professional Edition. 18th ed. Whitehouse Station, NJ: Merck, 2005.
McEvoy, Gerald K., ed. “Monoamine Oxidase Inhibitors.” AHFS Drug Information Pharm.D. Bethesda: American Society of Health-System Pharmacists, 2006.
First, Michael B., MD, and Laura J. Fochtmann, MD, eds. “Treating Major Depressive Disorder: A Quick Reference Guide.” The American Psychiatric Association’s Quick Reference Guides. 2nd ed. Arlington: American Psychiatric Press, 2000.
Jill U. Adams