Phenelzine (Nardil)

Phenelzine is an older, non-selective mono amine oxidase inhibitor. It has an irreversible effect on MAO, so its effect lasts for months.

Phenelzine is rarely used anymore; it is estimated that between 75,000 and 85,000 people world-wide take the drug. Although the patent has expired for Nardil, generic brands haven't emerged because the market is too small.

The Bottom Line: What You Really Need to Know

Uses of phenelzine

Phenelzine is approved for the treatment of anxiety, atypical depression, bulimia, depression that does not respond to other methods of treatment and social anxiety disorder. Phenelzine is rarely used as a first-line drug; rather it is reserved for instances when other medications don't work.

Dosage and instructions

Phenelzine therapy is started at 15 mg three times a day and rapidly increased to a total of 60 mg/day. The maximum recommended dose is 90 mg/day. It can take up to four weeks to get the full effect of phenelzine.

Once the maximum benefit has been obtained, the dose of phenelzine is slowly reduced to the lowest dose that maintains the benefit. This can be as low as 15 mg once a day. Therapy continues at that dose for as long as needed.

How phenelzine works

Phenelzine inhibits the function of mono amine oxidase, a complex enzyme system, throughout the body. MAO has many functions, one of which is regulation of various neurochemicals that are implicated in depression and anxiety.

Phenelzine is a non-selective MAOI and it inhibits both MAO-A and MAO-B.

The half-life (time it remains in your body) of phenelzine is short, but its effect on MAO is irreversible. It takes your body months to create new MAO, so the effect of phenelzine lasts for a long time.

Phenelzine is broken down in the liver and removed from the body through the urine.

Side Effects

Side effects with phenelzine are usually mild to moderate in severity and often resolve over time or with a reduction in dose. The most common side effects are:

Interactions with other medications and food

Phenelzine interacts with many medications and with foods containing the amino acid tyramine. Tyramine-containing foods have usually been aged-things like wine, cheese, aged meats, sauerkraut, chocolate and caffeine. If you are taking phenelzine, make sure you have a complete list of foods you need to avoid and do avoid those foods. Eating tyramine-containing foods while taking phenelzine can cause a hypertensive crisis and result in a stroke or heart attack.

There is a long list of medications that have serious and potentially fatal interactions with phenelzine. Some of them are:

Warnings, precautions and contraindications

Suicide risk: It is believed that all antidepressants can increase the risk of suicide, especially in the first weeks or months of therapy. Anyone who starts taking any new antidepressant should be closely monitored for signs of worsening depression and thoughts of harming self or others.

Medication interactions: Phenelzine can produce serious and even fatal interactions with many foods and medications. Make sure you have a complete list of foods that you should avoid. Also, make sure your doctor and pharmacist know about all of the medications you take, even if they are over-the-counter and you only take them occasionally. Make sure to include all vitamins and supplements on your medication list.

Activation of mania: Phenelzine can activate manic episodes in people with bipolar disease and can cause rapid cycling between mania and depression. Psychosis, self-destructive behavior and violence can occur. Depressed people should be screened for bipolar disease before beginning treatment with phenelzine.


In 2003, Pfizer reformulated the inactive ingredients in Nardil; users noticed a change in the effectiveness of the drug and began to experience side effects and loss of effectiveness of the drug. There have been complaints that the change was made to cut expenses in manufacturing the drug and that the manufacturer has been unresponsive to the needs of the customers.

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