Phenelzine, or Nardil as it’s typically called, is a monoamine oxidase inhibitor (MAOI) used to treat depression. Most side effects are minor, but severe symptoms, including seizures and serotonin syndrome, may occur, especially if taken without regard for a doctor’s instructions.

Phenelzine brand names

Phenelzine has one brand name, Nardil.

What is phenelzine prescribed for?

The most common use of phenelzine is to treat depression, specifically major depressive disorder but also for other disorders with symptoms of depression such as bipolar disorder. Usually, phenelzine is for patients who have not experienced improvement while on other antidepressant medications, such as fluoxetine.[2] Major depression has many hallmark symptoms, including:[1]

  • Feelings of sadness or emptiness
  • Loss of interest in once pleasurable activities
  • Changes in sleep patterns
  • Changes in eating patterns
  • Feelings of worthlessness, hopelessness, or guilt
  • Psychomotor agitation or retardation
  • Risk of suicidality

In addition, some people with major depression experience suicidal ideation, low energy, and difficulty concentrating.

In some cases, phenelzine is an option for treating panic and social anxiety disorders. Again, it’s usually only for cases in which the patient has not responded well to other drug treatments.[3]

Panic disorder is characterized by the sudden onset of panic, anxiety, and stress, usually for no apparent reason. These are commonly referred to as panic attacks. Symptoms include:[4]

  • Anxiety
  • Hot flashes
  • Trembling
  • Elevated heart rate
  • Sweating

Other symptoms include shortness of breath, tingling in the fingers, and dizziness. A 45-90mg dose of phenelzine has shown efficacy in treating these symptoms in open and controlled trials.[5]

Social anxiety disorder involves intense and persistent fears of being judged or watched by others. Symptoms include:[6]

  • Anxiety
  • Fear
  • Rapid heart rate
  • Trembling
  • Blushing

People with social anxiety disorder typically have difficulty making eye contact, especially with people they don’t know. Other symptoms include self-consciousness, avoidance of public places, and a persistent fear of being judged negatively.

In clinical trials, a combination of phenelzine and cognitive behavioral therapy (CBT) showed greater efficacy than either treatment alone. Likewise, the combination of CBT and phenelzine outperformed a placebo.[7]

How does phenelzine work?

Phenelzine sulfate is an MAOI. More specifically, it’s a nonselective MAOI A and B inhibitor.[3]

This means that phenelzine prevents several neurotransmitters (serotonin, dopamine, and norepinephrine) from breaking down. Likewise, phenelzine increases gamma-aminobutyric acid levels.

By preventing these neurotransmitters from breaking down, phenelzine gives them more time to work on their receptors in the brain. This action targets what researchers call the “monoamine deficiency hypothesis” [8] of depression, which posits that depression is related to a chemical deficiency of one of the neurotransmitters listed above.

The effect of phenelzine isn’t immediate, though. In most cases, symptom improvement takes about two weeks. However, mental health providers typically like to wait six to eight weeks to see how phenelzine affects their patients. If there’s little or no improvement after six to eight weeks, an increase in dosage may be in order.[3]

It’s common to start with a low dose of phenelzine sulfate and gradually increase the dosage (which helps minimize side effects). Because of this, it’s important to gradually reduce the dosage for the same reason.

How is phenelzine usually taken?

Phenelzine sulfate comes in tablet form and is taken three to four times a day. It can be taken with or without food.

As noted above, it’s common to begin with a low dose of phenelzine, say 7.5mg, then work up to a higher dosage. Most prescriptions are for 15-90mg, though this is highly dependent upon the individual and might be more or less depending on the specific circumstances.[1]

How long does phenelzine stay in your system?

According to the Federal Drug Administration, Nardil is absorbed in under an hour - the peak plasma concentration of the drug occurs about 43 minutes after ingesting it.[9]

Not only is Nardil quickly absorbed, but it’s also quickly metabolized. The FDA notes that the half-life of a 30mg dose of phenelzine is 11.6 hours. Approximately 73 percent of the dosage is eliminated in the urine within 96 hours of administration.[9] However, phenelzine remains in the system for up to two to three weeks at reduced levels.

Since trace amounts of phenelzine remain in your system for an extended period, you must speak with your doctor before taking other medications, particularly other types of antidepressants, to avoid drug-drug interactions.[2]

Phenelzine side effects

Phenelzine sulfate comes with a risk of mild to severe side effects. Fortunately, most common side effects are mild and can be relieved by adjusting the drug dosage. These include:[1]

  • Headache
  • Blurred vision
  • Dry mouth
  • Urinary retention and constipation
  • Sleepiness
  • Weight gain
  • Sexual dysfunction

Hypotension, or decreased blood pressure, is also a common side effect.

More severe adverse effects of phenelzine use include:[1]

  • Seizures
  • Skin rash
  • Liver dysfunction
  • High sodium levels
  • Suicidal thinking

Additionally, there are two extremely severe side effects of which to be aware: hypertensive crisis and serotonin syndrome. If any of the symptoms of these conditions present themselves you should seek immediate medical attention. 

A hypertensive crisis occurs with sudden and severe blood pressure increases (e.g., 180/120 or higher). When this happens, a myriad of symptoms might occur, including:[10]

  • Heart palpitations
  • Light sensitivity
  • Nausea and vomiting
  • Sweating
  • Neck stiffness and soreness
  • Headache pain in the occipital region

Serotonin syndrome is a potentially life-threatening condition that results from elevated levels of serotonin in the brain. Symptoms of serotonin syndrome range from mild to severe, including:[11]

  • Confusion
  • Diarrhea
  • Shivering
  • Fever
  • Severe muscle tightness
  • Seizures
  • Death

If you experience any mild phenelzine side effects discussed earlier, you must seek medical advice to make a dosage change. However, if you experience any of the severe symptoms listed above, you might be in danger of a life-threatening health issue. Talk to your doctor immediately, or call 9-1-1 if necessary.

Phenelzine precautions

Taking any drug requires a measured approach, which should begin with a conversation with your doctor about any drugs you’re currently taking. This includes prescription and non-prescription drugs, illicit drugs, herbal supplements, and vitamins.

A discussion about medical and mental health history in depressed patients is also in order before you take phenelzine sulfate. Tell your doctor if you have:[2]

  • Diabetes
  • High blood pressure
  • Seizures
  • Asthma
  • Hyperactivity or agitation
  • A movement disorder
  • Schizophrenia

Your doctor should also know if you’re pregnant, breastfeeding, or planning to become pregnant. Likewise, if you require surgery while on phenelzine, let the surgeon know ahead of time.

Additionally, you should avoid drinking alcohol as it can worsen the symptoms of depression while making the phenelzine side effects worse. Since phenelzine can make you tired, take care when driving a vehicle or operating machinery.

Phenelzine interactions

Phenelzine, like other MAOIs, has a long list of potential interactions with other drugs. Therefore, as outlined in the previous section, the most prudent approach is to provide your doctor with a detailed list of the substances you currently take or have recently taken. Doing so allows your doctor to check for possible interactions.

Having said that, certain drugs more commonly interact with Nardil than other types. This includes, but is not limited to, the following:[3]

  • Other antidepressants (e.g., mirtazapine, nefazodone, maprotiline)
  • Other MAOIs (e.g., metaxalone, procarbazine, tranylcypromine)
  • Medications for high blood pressure (e.g., methyldopa, beta-blockers)
  • Stimulants, like those used for attention deficit disorder (e.g., methylphenidate, atomoxetine)
  • Opioids (e.g., fentanyl, methadone, meperidine, tapentadol)

Additionally, tell your doctor if you’re taking medications for Parkinson’s, migraine headaches, or appetite suppression.

The most dangerous interactions occur between phenelzine and other drugs that increase serotonin levels in the brain (e.g., ecstasy, fluoxetine, duloxetine, St. John’s wort). Combining any of these drugs with phenelzine can increase the likelihood of developing serotonin syndrome.[3]

There are some foods you should avoid while taking phenelzine, too. Most notable are those with high levels of tyramine (e.g., pickled, smoked, or fermented foods), which can result in the onset of a hypertensive crisis.[1] These foods include:

  • Liver
  • Sauerkraut
  • Dry sausages (e.g., pepperoni, salami)
  • Aged cheeses
  • Beer
  • Wine

Also, avoid intaking foods or drinks with excessive caffeine (e.g., energy drinks) or chocolate.

Phenelzine storage

Nardil should be stored in its original container away from light, heat, and moisture in a climate-controlled area with temperatures between 59-86 degrees Fahrenheit.[9] The bathroom is not a good location for storing this drug, given its wide temperature and moisture fluctuations.

Keep Nardil out of sight and out of reach of children and pets. A safe place might be on the top shelf of a kitchen cupboard where kids and pets cannot reach.

Proper storage of Nardil is critical for preventing accidental overdoses in children and maintaining the medication's integrity. Keep an eye on the expiration date of the drug as well. Expired medications should be properly disposed of following the direction of your doctor or pharmacist.[12]

What to do if you overdose on phenelzine

The most common symptoms of phenelzine overdose include dilated pupils, involuntary muscle movements (especially of the eyes and face), and hypertension. However, overdose symptoms range widely from reasonably mild (e.g., agitation) to severe (e.g., coma).[3]

Call your doctor or 9-1-1 immediately if an overdose is suspected, as supportive treatment can help stabilize the situation. For example, diazepam can help reduce stimulation of the central nervous system, while chlorpromazine is another option for reducing the likelihood of a hypertensive crisis.[3]

When help arrives, tell them how much phenelzine was taken and when. This helps them understand the severity of the situation.

Frequently asked questions about phenelzine

Can you drink alcohol with phenelzine?

Combining phenelzine and alcohol isn't recommended. As discussed earlier, consuming alcohol might worsen the symptoms of depression. It can also increase the side effects associated with phenelzine, especially sedative properties.[1]

Are there any alternatives to phenelzine?

Other MAOIs might be used in place of phenelzine, such as isocarboxazid or tranylcypromine. However, usage of MAOIs is rare, given the increased likelihood of severe side effects. This is why MAOIs are considered a medication of last resort when newer medications (e.g., selective serotonin reuptake inhibitors or SSRIs) don’t provide the desired effect.[13]

Resources:

  1. Phenelzine (Nardil). (2020, December). National Alliance on Mental Illness. Retrieved October 31, 2022, fromhttps://www.nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Phenelzine-(Nardil)
  2. Phenelzine. (2017, May 15). MedlinePlus. Retrieved October 31, 2022, fromhttps://medlineplus.gov/druginfo/meds/a682089.html
  3. Sidhu, G, & Marwaha, R. Phenelzine. (2022, March 12). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:https://www.ncbi.nlm.nih.gov/books/NBK554508/
  4. National Health Service. (2022, March 29). Panic disorder. Retrieved October 31, 2022, fromhttps://www.nhs.uk/mental-health/conditions/panic-disorder/
  5. Saeed, S. A., & Bruce, T. J. (1998, May 15). Panic Disorder: Effective Treatment Options. American Family Physician, 57(10), 2405–2420. Retrieved October 31, 2022, fromhttps://www.aafp.org/pubs/afp/issues/1998/0515/p2405.html
  6. Social Anxiety Disorder: More Than Just Shyness. (n.d.) National Institute of Mental Health. Retrieved October 31, 2022, fromhttps://www.nimh.nih.gov/health/publications/social-anxiety-disorder-more-than-just-shyness
  7. Blanco, C., Heimberg, R. G., Schneier, F. R., Fresco, D. M., Chen, H., Turk, C. L., Vermes, D., Erwin, B. A., Schmidt, A. B., Juster, H. R., Campeas, R., & Liebowitz, M. R. (2010). A Placebo-Controlled Trial of Phenelzine, Cognitive Behavioral Group Therapy, and Their Combination for Social Anxiety Disorder. Archives of General Psychiatry, 67(3), 286–295.https://doi.org/10.1001/archgenpsychiatry.2010.11
  8. How Depression Affects the Brain. (2021, June 17). Yale Medicine. Retrieved November 1, 2022, fromhttps://www.yalemedicine.org/news/neurobiology-depression
  9. Nardil Medication Guide. (2006, July). Parke-Davis Division of Pfizer Inc, NY. Retrieved November 1, 2022, fromhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s036lbl.pdf
  10. Hypertensive Crisis: When You Should Call 911 for High Blood Pressure. (2022, October 14). www.heart.org.https://www.heart.org/en/health-topics/high-blood-pressure/understanding-blood-pressure-readings/hypertensive-crisis-when-you-should-call-911-for-high-blood-pressure
  11. Foong, A. L., Grindrod, K. A., Patel, T., & Kellar, J. Demystifying serotonin syndrome (or serotonin toxicity). (2018). Canadian family physician Medecin de famille canadien, 64(10), 720–727. Retrieved November 1, 2022, fromhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6184959/
  12. Phenelzine. (2019, November 25). Memorial Sloan Kettering Cancer Center. Retrieved November 2, 2022, fromhttps://www.mskcc.org/cancer-care/patient-education/medications/phenelzine
  13. National Health Service. (2021, November 4). Overview - Antidepressants. Retrieved November 2, 2022, fromhttps://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/antidepressants/overview/