Phenelzine (Nardil)

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Generic name: Phenelzine (FEN el zeen)

Brand name: Nardil®

• Tablets: 15 mg

All FDA warnings are at the end of this fact sheet. Please consult them before taking this medication.

What Is Phenelzine And What Does It Treat?

Phenelzine is an antidepressant medication that works in the brain. It belongs to the monoamine oxidase inhibitors (MAOIs) class of drugs. It is approved for the treatment of atypical, nonendogenous, or neurotic depression.

Symptoms of depression include:

• Depressed mood – feeling sad, empty, or tearful
• Feeling worthless, guilty, hopeless, and helpless
• Loss of interest or pleasure in your usual activities
• Sleep and eat more or less than usual (for most people it is less)
• Low energy, trouble concentrating, or thoughts of death (suicidal thinking)
• Psychomotor agitation (‘nervous energy’)
• Psychomotor retardation (feeling like you are moving and thinking in slow motion)
• Suicidal thoughts or behaviors

Phenelzine may help some or all these symptoms.

What Is The Most Important Information I Should Know About Phenelzine?

Do not stop taking phenelzine, even when you feel better. With input from you, your healthcare provider will assess how long you will need to take the medicine.

Missing doses of phenelzine may increase your risk for relapse in your symptoms.

Stopping phenelzine abruptly may result in one or more of the following withdrawal symptoms: irritability, nausea, dizziness, vomiting, nightmares, headache, and/or paresthesias (prickling, tingling sensation on the skin).

Depression is also a part of bipolar illness. People with bipolar disorder who take antidepressants may be at risk for “switching” from depression into mania. Symptoms of mania include “high” or irritable mood, very high self-esteem, decreased need for sleep, pressure to keep talking, racing thoughts, being easily distracted, frequently involved in activities with a large risk for bad consequences (for example, excessive buying sprees).

Medical attention should be sought if serotonin syndrome is suspected. Please refer to serious side effects for signs/symptoms.

Are There Specific Concerns About Phenelzine And Pregnancy?

The safety of phenelzine use during pregnancy or breastfeeding has not been established. In general, using MAOIs is not recommended during pregnancy as the mother could develop hypertensive crisis, which could be detrimental to the fetus If you are planning on becoming pregnant, or breastfeeding notify your health care provider to best manage your medications. People living with depression who wish to become pregnant face important decisions. Untreated depression has risks to the fetus, as well as the mother. It is important to discuss the risks and benefits of treatment with your doctor and caregivers.

What Should I Discuss with My Health Care Provider Before Taking Phenelzine?

• Symptoms of your condition that bother you the most
• If you have thoughts of suicide or harming yourself
• Medications you have taken in the past for your condition, whether they were effective or caused any adverse effects
• If you experience side effects from your medications, discuss them with your provider. Some side effects may pass with time, but others may require changes in the medication.
• Any other psychiatric or medical problems you have, including a history of bipolar disorder
• If you have a family history of diabetes or heart disease, liver disease, high blood pressure, brain blood vessel disease, history of headache
• All other medications you are currently taking (including over the counter products, herbal and nutritional supplements) and any medication allergies you have
• Other non-medication treatment you are receiving, such as talk therapy or substance abuse treatment. Your provider can explain how these different treatments work with the medication.
• If you are pregnant, plan to become pregnant, or are breastfeeding
• If you drink alcohol or use drugs

How Should I Take Phenelzine?

Phenelzine is usually taken three to four times per day with or without food.

Typically patients begin at a low dose of medicine and the dose is increased at least 60 mg a day at a rapid pace per patient’s tolerance.

The dose usually ranges from 15 mg to 90 mg per day. Only your healthcare provider can determine the correct dose for you.

Consider using a calendar, pillbox, alarm clock, or cell phone alert to help you remember to take your medication. You may also ask a family member or friend to remind you or check in with you to be sure you are taking your medication.

What Happens If I Miss A Dose Of Phenelzine?

If you miss a dose of phenelzine take it as soon as you remember, unless it is closer to the time of your next dose. Discuss this with your healthcare provider. Do not double your next dose or take more than what is prescribed.

What Should I Avoid While Taking Phenelzine?

Avoid drinking alcohol or using illegal drugs while you are taking antidepressant medications. They may decrease the benefits (e.g., worsen your condition) and increase adverse effects (e.g., sedation) of the medication.

Special Dietary Considerations: Foods rich in tyramine and may cause a sudden and severe high blood pressure (hypertensive crisis). Avoid high protein food that has undergone protein break down via aging, fermentation, pickling, smoking, or bacterial contamination. Also avoid beverages containing tyramine. Food freshness is also important; avoid any food that may potentially be spoiled, improperly refrigerated, stored, or handled. Ask your provider to give you a complete list of food and drinks containing tyramine.

Example of food to avoid include:

• Dry sausage (salami, pepperoni)
• Cheeses (aged cheeses including parmesan, aged cheddar, bleu cheese)
• Beer, wine
• Pickled herring
• Liver
• Fava or broad bean pods
• Sauerkraut
• Avoid foods/beverages with excessive amounts of caffeine/chocolate

These dietary considerations should be taken into consideration for 2 weeks even after phenelzine is discontinued.

What Happens If I Overdose With Phenelzine?

If an overdose occurs, call your doctor or 911. You may need urgent medical care. You may also contact the poison control center at 1-800-222-1222.

A specific treatment to reverse the effects of phenelzine does not exist.

What Are The Possible Side Effects Of Phenelzine?

Common side effects

• Sedation
• Dry mouth
• Weight gain
• Decreased blood pressure (hypotension)
• Headache
• Constipation
• Sexual dysfunction
• Blurred vision
• Urinary retention

Rare side effects

• Liver dysfunction
• Skin rash
• Seizures
• Edema of glottis
• Hypertensive crisis; especially if low tyramine diet is not followed
• Serotonin Syndrome
• Depression, suicidal thought, and suicide

Hypertensive crisis (symptoms may include occipital headache-start in the back and radiate to the front, heart palpitations, nausea/vomiting, neck stiffness/soreness, light sensitivity, sweating)

Serotonin syndrome (symptoms may include shivering, diarrhea, confusion, severe muscle tightness, fever, seizures, and death)

Are There Any Risks For Taking Phenelzine For Long Periods Of Time?

To date, there are no known problems associated with long term use of phenelzine. It is a safe and effective medication when used as directed.

What Other Medications May Interact With Phenelzine?

Phenelzine should not be taken with or within 2 weeks (5 weeks for fluoxetine) of any other mental health medications including other antidepressants, mood stabilizers, antipsychotics, and ant-anxiety medications. Phenelzine may also interact with some pain medication, medications for migraines, amphetamines, and antibiotics. Please inform your healthcare providers of all your current medications and any substance use at the time of prescribing to avoid any potential side effects.

There is an increased risk of serotonin syndrome when phenelzine is used with other medications that increase serotonin, such as other antidepressants, migraine medications called “triptans” (e.g., Imitrex®), some pain medications (e.g., tramadol [Ultram®]), amphetamines, and the antibiotic linezolid (Zyvox®).

The following medications may increase the levels and effects of phenelzine: alcohol, alfuzosin, amantadine, antipsychotics, barbiturates, blood pressure lowering agents, buprenorphine, buspirone, carbamazepine, cyclobenzaprine, fentanyl, ipratropium (oral inhalation), levodopa, methadone, methylene blue, oxycodone, opioid analgesics, pentoxifylline, pheniramine, phosphodiesterase 5 inhibitors (including sildenafil), tramadol, tetrabenazine, valbenazine

The following medications may decrease the levels and effects of phenelzine: acetylcholinesterase inhibitors, amifampridine, cyproheptadine, domperidone

Phenelzine may increase the levels and effects of: antipsychotics, atomoxetine, bupropion, cyproheptadine, deutetrabenazine, dopamine, dextromethorphan, codeine, heroin, hydrocodone, lithium, methylphenidate, morphine, mirtazapine, MAO-Is, norepinephrine, opioid analgesics, pindolol, SSRIs, SNRIs, topiramate, tramadol, tricyclic antidepressants

Phenelzine may decrease the levels and effects of acetylcholinesterase inhibitors, gastrointestinal agents, amifampridine, domperidone, and nitroglycerin

How Long Does It Take For Phenelzine To Work?

Sleep, energy, or appetite may show some improvement within the first 1-2 weeks. Improvement in these physical symptoms can be an important early signal that the medication is working. Depressed mood and lack of interest in activities may need up to 6-8 weeks to fully improve.

Summary of Black Box Warnings

Suicidal Thoughts or Actions in Children and Adults

Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications. This risk may persist until significant remission occurs.

In short-term studies, antidepressants increased the risk of suicidality in children, adolescents, and young adults when compared to placebo. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24. Adults age 65 and older taking antidepressants have a decreased risk of suicidality. Patients, their families, and caregivers should be alert to the emergence of anxiety, restlessness, irritability, aggressiveness and insomnia. If these symptoms emerge, they should be reported to the patient’s prescriber or health care professional. All patients being treated with this medication for depression should watch for and notify their health care provider for worsening symptoms, suicidality and unusual changes in behavior, especially during the first few months of treatment.

Last Reviewed: December 2024

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Important Disclosure: This information is being provided as a community outreach effort of the American Association of Psychiatric Pharmacists. This information is for educational and informational purposes only and is not medical advice. This information contains a summary of important points and is not an exhaustive review of information about the medication. Always seek the advice of a physician or other qualified medical professional with any questions you may have regarding medications or medical conditions. Never delay seeking professional medical advice or disregard medical professional advice as a result of any information provided herein. The American Association of Psychiatric Pharmacists disclaims any and all liability alleged as a result of the information provided herein.

©2024 The American Association of Psychiatric Pharmacists (AAPP) and the National Alliance on Mental Illness (NAMI). AAPP and NAMI make this document available under the Creative Commons Attribution-NoDerivatives 4.0 International License. Last Updated: June 2024.