Phenelzine is classified as a monoamine oxidase (MAO) inhibitor. In the United States, phenelzine is sold under the brand name Nardil.


Phenelzine is used to treat certain types of serious depression and severe depression complicated by severe anxiety that do not respond to other antidepressant drugs.


Phenelzine is a member of a class of drugs called monoamine oxidase inhibitors. Monoamine oxidase, or MAO, is an enzyme found throughout the body. In the brain , MAO breaks down norepinephrine and serotonin, two naturally occurring chemicals that are important in maintaining mental well-being and preventing depression. Monoamine oxidase inhibitors, such as phenelzine, reduce the activity of MAO. Less norepinephrine and serotonin are broken down, so their levels rise. This helps to lift depression.

Phenelzine is effective for treating depression, especially complicated types of depression that have not responded to more traditional antidepressants. However, phenelzine also affects the MAO enzyme in many other areas of the body. This accounts for the large number of serious side effects and drug interactions it causes.

Recommended dosage

Adults are usually started on 15 mg of phenelzine three times per day. This dosage can be increased to a maximum of 90 mg per day if lower doses are not effective, and the patient can tolerate the higher dose without excessive side effects. After the maximum benefits are achieved, the dosage is usually lowered over several weeks to the lowest level that is effective. This could be as little as 15 mg daily or every other day.

In general, phenelzine is not recommended for people over the age of 60. When it is used by the elderly, the starting dosage is usually 15 mg taken in the morning. This dose may be gradually increased over time to a maximum of 60 mg. Phenelzine is not frequently given to children under the age of 16, and recommended dosage in such cases has not been established.

Phenelzine can be taken with food or on an empty stomach. It should not be taken close to bedtime, because it can interfere with sleep. The benefits of this drug may not become apparent for as long as four to eight weeks. Patients should be aware of this and continue taking the drug as directed even if they do not see an immediate improvement.


People with a history of congestive heart failure, high blood pressure, cardiovascular disease, headache, kidney disease, or liver disease should not take phenelzine or, if they do take it, they should be under careful medical supervision and monitoring. Children under the age of 16 and people with a history of low blood pressure, bipolar disorders , angina, hyperactivity, diabetes mellitus, seizures , suicidal thoughts, and overactive thyroid should discuss the risks and benefits of this drug with their physician, and a decision to treat should be made on an individual basis. If these patients receive phenelzine, it should be taken only under the careful supervision of a doctor. Evidence suggests that phenelzine should not be used during pregnancy or while nursing.

People taking phenelzine should get up slowly from a reclining position to prevent dizziness. Those who use phenelzine should use caution when operating heavy machinery or performing hazardous activities that require alertness.

It is very important for the doctor to determine the lowest dosage of phenelzine that produces benefits. When this dosage is exceeded, side effects and interactions increase substantially. Over-the-counter medications that contain decongestants or dextromethorphan (for example, some cough syrups and cold remedies) should not be taken while using phenelzine (see "Interactions," below). In addition, foods and beverages that contain tyramine should not be eaten while using this medication. These foods include yeast or meat extracts, fermented sausage, overripe fruit, sauerkraut, cheese, and fava beans. Phenelzine should not be used within two weeks of undergoing surgery that requires anesthesia.

Side effects

The enzyme monoamine oxidase regulates functions throughout the body. Phenelzine decreases the activity of monoamine oxidase in all the areas of the body where it exists, not just in the brain. This is why phenelzine is capable of causing a wide variety of side effects in many different organ systems.

The most common and unavoidable side effects associated with phenelzine use are swelling of the feet and ankles, low blood pressure upon arising from a reclining position, and insomnia if taken near bedtime. Mild side effects and ones that are not frequent include skin rash, headache, dizziness, confusion, memory impairment, drowsiness, weakness, shakiness, muscle twitching, constipation, indigestion, appetite changes, and dry mouth. Although these side effects are considered mild, they should be reported to the treating doctor.

More serious side effects include hepatitis coupled with jaundice, high blood pressure crisis, excessive nervousness, and changes in heart rate. The high blood pressure crisis involves significantly increased blood pressure, severe headache, heart palpitations, nausea, vomiting, and sweating. These symptoms need immediate medical attention. Sexual function can be affected in both men and women.


Phenelzine interacts with a long list of drugs. Some of these interactions can cause death. This section is not a complete list of interactions, but it includes the most serious ones. Patients must make sure that every health care professional who takes care of them (for example, doctors, dentists, podiatrists, optometrists, pharmacists, nurses) knows that they take phenelzine, as well as all of the other prescription, nonprescription, and herbal drugs they take.

All foods and beverages containing tyramine need to be avoided while taking this medication. Coffee, tea, and cola beverages should be restricted to one serving per day. Alcohol should not be used while taking phenelzine, because it can significantly increase blood pressure.

Any type of amphetamine and other stimulant should not be used, because this combination can increase blood pressure to dangerously high levels. Phenelzine should not be combined with other antidepressants, because of increased risk of dangerously high blood pressure and manic episodes. Patients taking phenelzine should stop the drug, then wait at least 14 days before starting any other antidepressant. The same holds true when discontinuing another antidepressant and starting phenelzine. Phenelzine combined with barbiturates can prolong the effects of barbiturates.

Phenelzine combined with clomipramine (Anafranil) can cause death. Diet drugs and decongestants containing compounds such as dextromethorphan should not be combined with phenelzine because of an increased risk of seizures and agitation. Phenelzine can decrease the effectiveness of high blood pressure drugs, such as guanadrel (Hylorel) and guanethidine (Ismelin). Phenelzine combined with the Parkinson disease drug levodopa (Dopar, Larodopa) can produce severely high blood pressure. Lithium should not be used with phenelzine because of the risk of developing extremely high fever. Phenelzine can prolong the effects of muscle relaxants when the two are combined.



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Mark Mitchell, M.D.

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