Evidence Based
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Phenelzine (Nardil) Uses, Side Effects, Diet & Natural Options

Written by Mathew Eng, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology) | Written by Mathew Eng, PharmD | Reviewed by Ana Aleksic, MSc (Pharmacy) | 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, side effects, and the best natural alternatives.

Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific and clinical literature. Please discuss your medications with your doctor.

What Is Phenelzine?

Phenelzine sulfate, also known as Nardil, is a monoamine oxidase inhibitor. Monoamine oxidase inhibitors (MAOIs) are effective antidepressants [1].

Phenelzine was first recognized in the 1950s when its clinical application became evident, and it has since gained a great deal of attention as an all-encompassing treatment for multiple mental disorders. From anxiety to PTSD, phenelzine has been a prominent player in the psychological pharmaceutical industry for some time now.

Mechanisms of Action

1) Inhibits MAO

Phenelzine is a non-selective monoamine oxidase inhibitor (MAOI) that inhibits both type A and B MAOs. MAOs inactivate monoamine and indolamine neurotransmitters that include dopamine, epinephrine, norepinephrine, serotonin, and tyramine [2].

MAO inhibitors, such as phenelzine, are also capable of increasing and decreasing insulin release [3].

2) Other Mechanisms

Phenelzine decreases tyrosine aminotransferase, an enzyme thought to play a role in tyrosinemia type II (Richner-Hanhart syndrome), hepatitis (a virus that attacks the liver), and hepatic carcinoma (liver cancer) recovery in the livers of rats [4, 5].

In rat brains, phenelzine also decreases the aromatic L-amino acid decarboxylase activity, which promotes neurotransmitter production and plays a role in metabolic pathways in the brain [4, 6].

Uses

1) Major Depression and Anxiety

A study of patients with major depression found that 45 and 60 mg daily doses of phenelzine were significantly more effective at preventing depression relapse than placebo [7].

In addition, in cases of psychotic, probably psychotic, and non-psychotic depression, all forms were improved with phenelzine [8].

A study of 117 neurotic patients, phenelzine reduced anxiety and depression symptoms [9].

Phenelzine also treated chronic daily headaches associated with depression and anxiety in a study of 11 depression patients [10].

2) Phobias

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

Phenelzine reduced subjective anxiety during exposure to predetermined phobias in a study of 40 social phobia patients [12].

In a 6-person study, phenelzine was effective in treating social phobias that had been unresponsive to other treatments [13].

3) Borderline Personality Disorder

In a study of 54 borderline personality patients, phenelzine decreased depression and irritability while increasing excitement and reactivity [14].

Phenelzine was tested against imipramine and placebo. It demonstrated the highest percentage of improvement in the symptoms of 60 patients who had atypical depression and borderline personality disorder [15].

4) PTSD

Five patients treated with phenelzine felt calmer and stopped having nightmares and flashbacks of traumatic experiences during war. Their behavior was also significantly less violent and their startle reactions were lessened [16].

Phenelzine also significantly reduced sleep disturbance in combat veterans [17].

In a study of 34 male veterans, phenelzine supplementation (15 to 75 mg daily) significantly reduced PTSD symptoms. The subjects reported less anxiety, nightmares, flashbacks, and intrusive thoughts. However, their emotional numbing, emotional distance, and suppression of memories did not improve [18].

5) Mutism

Phenelzine successfully cured selective mutism (anxiety disorder where people who can normally speak cannot speak in certain situations) in a case study [19].

It also cured selective mutism in four children, ages 5½ to 7. There was no recurrence of mutism after discontinuing phenelzine use [20].

6) May Help with Cocaine Addiction

Phenelzine corrected neurotransmitter defects caused by chronic cocaine usage in 26 addiction patients. This reduced their craving for cocaine and successfully treated their cocaine addiction [21].

7) Bulimia

In a study of 50 bulimic patients, phenelzine decreased binge eating frequency. However, its side effects caused some patients to discontinue phenelzine use [22].

It also decreased bulimic and depressive symptoms in another 24 person study [23].

8) OCD

In a study of 30 OCD patients, phenelzine decreased obsessive-compulsive and depressive symptoms [24].

Dosage

Dosages for phenelzine often vary depending on its use:

In patients recovering from acute depression, 45 – 60 mg/day is recommended [25].

For the treatment of social anxiety disorder, a dose of 66 mg/day is effective [13].

In patients with depression, anxiety, and severe phobias, both 45 and 90 mg daily doses of phenelzine improved their symptoms. However, 90 mg was more effective [26].

For curing selective mutism in children, 30 – 60 mg/day of phenelzine is effective [20].

For treating PTSD, 60 mg/day is an effective treatment dosage [17].

Limitations and Caveats

Many of phenelzine’s benefits have yet to be investigated outside of animal studies. Physicians should be cautious when prescribing phenelzine for any unapproved indication. All MAOIs require a prescription.

Phenelzine Side Effects

Phenelzine can be addictive [27].

Phenelzine has been reported to cause death, but only when taken at abnormally high doses (10-50 times greater than a clinical dosage) [28].

Phenelzine has, in rare cases, caused liver failure [29].

Common side effects include [13, 10, 30, 31]:

  • Weight gain
  • Low blood pressure
  • Hypertension (high blood pressure)
  • Tachycardia (abnormally rapid heart rate)
  • Sexual dysfunction
  • Urinary hesitancy (involuntary hesitation during urination)
  • Myoclonic jerks (brief involuntary muscle twitching)
  • Constipation
  • Dry mouth
  • Headache

Less Common Side Effects

1) Reduces Blood Levels of Vitamin B6

In one study, all 19 patients taking phenelzine had reduced vitamin B6 blood levels by an average of 54% compared to the control group [32].

Pyridoxine (vitamin B6) deficiency developed in two young men, and six patients in a separate study, that were treated with phenelzine [33, 34].

2) May Cause Heart Failure

High doses of phenelzine may cause acute myocarditis, inflammation of the middle layer of the heart wall [31].

A 23-year-old woman had massive phenelzine overdose (2,760 mg) and developed severe and unexplained hypotension, impaired left ventricular function, and acute myocarditis. She died 3 days after [35].

3) May Cause Low Blood Sugar

Based on the cross-referencing of depression, antidepressant drugs, and diabetes, phenelzine and other MAOI have induced hypoglycemia (low blood sugar) [36].

4) Mental Health Complications

A reported case of delusional parasitosis (the mistaken belief that one is being infested by parasites) has been associated with taking phenelzine [37].

Phenelzine is also associated with increased hostility [38].

Drug Interactions

Phenelzine should not be taken in conjunction with general anesthetics, as it prolongs the effects of these medications, such as suxamethonium [39].

When taken with venlafaxine or morphine, phenelzine can cause serotonin syndrome. Serotonin syndrome is a potentially life-threatening condition caused by excessive stimulation of serotonin [40, 41].

Rapid switch from phenelzine to tranylcypromine may induce stroke [42].

Phenelzine may cause delirium when coupled with L-tryptophan [43].

In combination with ginseng, phenelzine may cause sleeplessness, nervousness, hypertension, euphoria, and headaches [44].

Phenelzine Antidote

There is no specific antidote for phenelzine poisoning (or MAOI poisoning in general). Charcoal can reduce its absorption, but only if very shortly after taking the drug. Once signs of poisoning appear, activated charcoal will not be effective [45].

If you suspect phenelzine poisoning or are concerned about someone close to you, go to the nearest emergency department straight away. Phenelzine poisoning can be life-threatening [45].

Specialists at the emergency department will treat the poisoning depending on your symptoms and health status [45].

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. But taking an MAO inhibitor will disrupt this process [46].

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 [46].

For this reason, MAOI users should avoid foods high in tyramine. Research shows that consuming just 6 mg of tyramine can lead to symptoms [47].

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 [48].

Some examples of foods to avoid include [48, 47, 49]:

  • 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 [49].

Natural Alternatives

There are several plant-derived compounds that have antidepressant effects. Some of these natural substances inhibit the MAO enzyme similar to phenelzine.

The following list details the natural alternatives that have been best studied in clinical trials.

Remember: You should always consult your doctor before changing or stopping your medications, especially with phenelzine. Taking multiple MAOIs can cause serious side effects and even life-threatening poisoning.

It’s also important to let your doctor know of all the supplements you are currently taking to avoid any potential interactions.

1) St John’s Wort

St John’s wort (Hypericum perforatum) is a flowering plant that has historically been used as a medicinal herb [50].

Cell studies indicate that St John’s wort inhibits both MAO-A and MAO-B, similar to phenelzine. It also may block the reuptake of serotonin, dopamine, and norepinephrine, which is how newer antidepressants work [51].

St John’s wort is just as effective as SSRIs, a commonly prescribed group of antidepressants. Also, fewer side effects are reported with St John’s wort. This is all according to a recent review of 27 clinical trials including almost 4k patients [52].

A different review of 35 clinical trials and ~7k people revealed similar results [53].

However, there are a few things to note.

St John’s wort is only effective in mild-to-moderate depression. It is not helpful for severe symptoms. It’s also not clear if it helps with suicide risk [52, 53].

Another issue is that there is little information on long-term effects [52, 53].

St John’s wort also suffers from many of the same problems that phenelzine faces. It may lead to serious interactions with other medications and food [54].

Bottom Line

St John’s wort has the same effectiveness as many commonly used antidepressants, but only for mild-to-moderate depression. It also appears to cause fewer side effects [52, 53].

But be careful: St John’s wort has many of the same drug and food interactions as phenelzine. You should consult your doctor if you plan to use St John’s wort to avoid any issues [54].

2) Curcumin

Curcumin is one of the main compounds found inside turmeric. Research has identified many potential health benefits of curcumin, including antidepressant effects [55].

Studies using cells suggest that curcumin inhibits MAO-A and MAO-B. It may also directly work on serotonin receptors [56, 57].

Curcumin is safe and effective for depression, according to one analysis of 6 clinical trials with 377 patients [58].

Specifically, curcumin improves depression and anxiety symptoms. No side effects were reported in any of the studies. Other reviews have found similar results [58, 59].

Interestingly, one study found no difference between low dose (250 mg twice a day) and high dose (500 mg twice a day) curcumin – both were equally effective for depression [60].

A major issue with curcumin is that it’s poorly absorbed and has very low bioavailability – only 1% according to some studies [61].

This is why curcumin is often formulated as liposomes, theracurmin, or with other compounds, to improve absorption. A common combination is with piperine (black pepper), which can increase bioavailability by up to 2,000%. Many studies that look at curcumin use this specific combination [62, 63, 61, 59].

Bottom Line

Curcumin may safely improve depression and anxiety, even at moderate doses. But it works only if taken as an adequate formulation (liposomal, theracurmin, or in combination with piperine).

3) Rhodiola rosea

Several countries use the plant Rhodiola rosea as a traditional remedy for fatigue, stress, and depression [64].

Compounds inside Rhodiola rosea are able to strongly inhibit both MAO-A and MAO-B, according to cell studies [65].

A study of 57 people found that Rhodiola rosea improves depression symptoms, but not as well as sertraline (Zoloft), a commonly prescribed antidepressant. However, about 30% fewer side effects were reported with Rhodiola rosea [66].

Rhodiola rosea extract may also reduce anxiety, stress, anger, and confusion, according to a study of 80 people [67].

Bottom Line

Rhodiola’s antidepressant effects are similar to phenelzine, but much weaker. On the upside, side effects are rare and it may help people with mild symptoms.

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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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