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Phenelzine (Nardil) Uses, Side Effects, & Diet

Written by Mathew Eng, PharmD | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Mathew Eng, PharmD | Last updated:

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Phenelzine is only approved for the treatment of major depressive disorder, although it’s sometimes prescribed for other mental health issues. If your doctor prescribed you this drug, you’ll need to adapt your diet to avoid blood pressure spikes. Read on to learn more about phenelzine uses and side effects.

What Is Phenelzine (Nardil)?

Phenelzine (brand name Nardil) is a prescription medication that is primarily used to treat depression. It is also sometimes used for other mental disorders, such as anxiety and PTSD.

Phenelzine belongs to a group of medications called monoamine oxidase inhibitors (MAOIs). MAOIs are among the earliest drugs used for depression. However, due to their many drug interactions and diet restrictions, MAOIs today are usually reserved as last-line treatment options [1].

How Does It Work?

Phenelzine is a monoamine oxidase inhibitor (MAOI), which means it inhibits the MAO enzyme. This enzyme is responsible for breaking down neurotransmitters, such as dopamine, epinephrine, norepinephrine, serotonin, and tyramine [2].

Phenelzine is classified as a non-selective and irreversible MAOI.

  • Non-selective means that phenelzine inhibits both types of MAO (the A and B types).
  • Irreversible MAOIs cannot be detached from the MAO enzyme once it is bound, which means the effects of the drug may persist for 2-3 weeks after discontinuation.

There is also some evidence that MAOIs inhibit other enzymes, such as ALA-T and GABA-T [3, 4].

Phenelzine Uses

FDA-Approved Uses

1) Depression

Phenelzine is FDA-approved for the treatment of depression. However, physicians commonly do not use phenelzine as a first choice antidepressant due to its numerous drug interactions and dietary restrictions [2].

Despite this decrease in popularity in recent years, research does show that phenelzine is safe and effective for treating symptoms of depression. In fact, MAOIs appear to be particularly effective for specific types of depression [2].

For example, research shows that MAOIs like phenelzine may be superior to other common antidepressants for the treatment of atypical depression, a specific form of depression where mood can improve in response to positive events [5].

There is some evidence that MAOIs may be particularly effective for depression associated with bipolar disorder. Phenelzine is also an option for patients who fail to respond to other antidepressants [2].

Off-Label Uses

Phenelzine is sometimes used for several off-label conditions, which we’ll discuss in the following sections. If you are prescribed phenelzine, always take the medication as directed by your doctor.

2) Dysthymia

Phenelzine is sometimes used to treat dysthymia (also known as persistent depressive disorder) a mood disorder similar to depression, but where symptoms are usually milder and longer lasting [6].

A 6-week double-blind trial of 32 patients with dysthymia found that phenelzine may be more effective at reducing depressive symptoms compared to imipramine, another common antidepressant [7].

3) Borderline Personality Disorder

A placebo-controlled trial of 53 patients with borderline personality disorder suggests that phenelzine may reduce symptoms of depression and irritability, while increasing excitement and reactivity [8].

4) Social Phobia

In an 11 person study, phenelzine improved social phobias and reduced interpersonal hypersensitivity [9].

According to a double-blind study of 40 patients with social phobia, phenelzine may reduce subjective anxiety during phobic experiences [10].

In a 6-person study, phenelzine was effective in treating social phobias that had been unresponsive to other treatments [11].

5) PTSD

A small study looked at the effects of phenelzine in 5 patients with PTSD who did not respond to other medications. The patients reported feeling calmer and experiencing fewer traumatic nightmares and flashbacks. Instances of startled reactions and violent outbursts also decreased [12].

Another study of 25 war veterans found that phenelzine reduces sleep disturbances. However, the medication did not improve any other symptoms of PTSD in the study [13].

In a study of 34 male veterans, phenelzine improved PTSD symptoms, including reduced anxiety, nightmares, flashbacks, and intrusive thoughts. However, emotional numbing, emotional distance, and suppression of memories did not improve [14].

6) Bulimia

In a placebo-controlled study of 50 bulimic patients, phenelzine significantly decreased binge eating frequency. However, its side effects caused some patients to discontinue phenelzine use [15].

Another study of 24 patients suggests that phenelzine improves depressive and bulimic symptoms better than imipramine (an antidepressant) or placebo [16].

7) OCD

In a study of 30 OCD patients, phenelzine decreased obsessive-compulsive and depressive symptoms [17].

Phenelzine Diet

Individuals taking phenelzine (or any type of MAOI) have to be careful about what they eat.

The problem comes from foods and drinks that contain the amino acid tyramine. Normally, tyramine is metabolized by MAO in the body. Taking an MAO inhibitor can disrupt this process [18].

High levels of tyramine can cause blood pressure to skyrocket, leading to a condition called hypertensive crisis. This condition is potentially life-threatening and requires immediate care [18].

For this reason, MAOI users should avoid foods high in tyramine. Research shows that consuming just 6 mg of tyramine can lead to symptoms [19].

Tyramine is naturally found in foods that contain protein, like meats. Foods that have been aged, cured, smoked, or processed are usually high in tyramine [20].

Some examples of foods to avoid include [20, 19, 21]:

  • Cured meats (air-dried sausage, pepperoni)
  • Aged cheeses (blue cheeses, Swiss)
  • Pickled or fermented foods (sauerkraut, pickles, kimchi)
  • Fermented soybean products (soy sauce, tempeh)
  • Chocolate
  • Alcoholic beverages (especially tap beers)
  • Dried or overripe fruits (raisins, prunes)

These are some common examples, but this is not a complete list. If you’re unsure about a certain food, it’s better to consult your doctor first. A good strategy is to try to stick to fresh foods as much as possible [21].

Phenelzine Safety

Side Effects

Below are some reported side effects of phenelzine. If any side effects persist or worsen, let your doctor know. This is not a complete list of possible side effects. Tell your doctor if you experience any serious side effects or notice any effects not listed here.

Some common side effects include [22]:

  • Dizziness
  • Headache
  • Drowsiness
  • Trouble sleeping
  • Tiredness
  • Tremors and twitching
  • Constipation
  • Dry mouth
  • Weight gain
  • Low blood pressure
  • Swelling
  • Sexual dysfunction

Some serious side effects include [22]:

  • Behavioral changes
  • Severe stomach pain
  • Persistent nausea or vomiting
  • Seizures
  • Chest pain
  • Frequent or severe headaches

Warnings

Increased Risk of Suicide

Antidepressants are associated with a higher risk of suicidal thinking and behavior, especially in children and young adults. Those taking phenelzine should be monitored and any changes in behavior should be reported to a doctor [22].

Hypertensive Crisis

As mentioned earlier, phenelzine can potentially cause a condition called hypertensive crisis where blood pressure dramatically increases. This condition can be fatal and requires immediate medical attention. Some signs of hypertensive crisis include [22]:

  • Severe chest pain
  • Persistent or severe headache
  • Shortness of breath
  • Seizures
  • Persistent nausea or vomiting

Certain foods, drinks, and medications can interact with phenelzine to cause this condition. Patients taking phenelzine should discuss with their doctor what foods and medications to avoid.

Pregnancy and Breastfeeding Considerations

Due to a lack of clinical research, it’s unclear how phenelzine affects the fetus. Evidence from some animal studies suggests there may be some negative effects. Phenelzine should only be used during pregnancy if a doctor determines that the benefits outweigh risks [23].

It is also unclear if phenelzine is safe to use while breastfeeding. Again, a doctor will decide if phenelzine can be used during breastfeeding [23].

Contraindications

People who are sensitive or allergic to phenelzine or any of its components should avoid using this medication [22].

Phenelzine should also not be taken with certain medications, which will be detailed in the next section.

Drug Interactions

Phenelzine has many potentially serious drug interactions, some of which are listed below. However, this is not a complete list, let your doctor know of all the medications you are currently taking to avoid any unexpected interactions.

  • Cold and cough medications
  • Other antidepressants
  • Certain blood pressure medications, including atenolol and clonidine
  • Stimulants, such as amphetamines, epinephrine, and phenylalanine
  • Anesthesia
  • Certain pain medications, including meperidine and tramadol
  • Tobacco

Phenelzine Dosage

The dosing of phenelzine can vary. Always take this medication as directed by a doctor.

For depression in adults, an initial dose is typically 15 mg three times a day.

This dose is usually then increased rapidly up to 60 to 90 mg per day, depending on patient response and tolerance. Once a maximum benefit dose is reached, doses are typically reduced until a maintenance dose is established.

Similar to other antidepressants, it may take several weeks to several months before patients may see any effect from this medication.

Phenelzine should not be abruptly discontinued. If the medication needs to be stopped, the dose must be gradually lowered to minimize withdrawal symptoms.

When switching to or from phenelzine to another antidepressant, patients typically must wait a certain period of time before starting the new medication. Switching medications too quickly may cause side effects [22].

About the Author

Mathew Eng

Mathew Eng

PharmD
Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.
Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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