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Because of its wide range of application, phenelzine has been evaluated through countless case studies for nearly seventy years within the scientific research community. Whether the drug is being used to improve social phobias, alleviate depression, or treat various addictions, it has undoubtedly proven it’s useful clinical application.   

Read on to learn the many benefits phenelzine may bring to one’s life and the drawbacks that it possesses.

Note: 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 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 [R].

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 ailments. From anxiety to PTSD, phenelzine has been a prominent player in the psychological pharmaceutical industry for some time now.

Mechanisms of Phenelzine

1) Phenelzine Inhibits MAO

Phenelzine decreases both monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase activities. Fat tissue contains high amounts of these enzymes. In turn, phenelzine directly decreases fat cell storage and production [R].

MAOs inactivate monoamine and indolamine neurotransmitters that include dopamine, epinephrine, norepinephrine, serotonin, and tyramine [R].

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

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 rat livers [R, R].

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

Uses of Phenelzine

1) Phenelzine Treats Major Depression and Anxiety

In a study (DB-RCT) of patients with major depression, 45 and 60 mg daily doses of phenelzine were significantly more effective at preventing depression relapse than the placebo [R].

Additionally, in cases of psychotic, probably psychotic, and nonpsychotic depression, all forms were improved with phenelzine [R].

In a study (DB-RCT) of 117 neurotic patients, phenelzine reduced anxiety and depression symptoms [R].

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

2) Phenelzine Improves Phobias

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

Phenelzine reduced subjective anxiety during exposure to predetermined phobias in a study (DB-RCT) of 40 social phobia patients [R].

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

3) Phenelzine Helps Treat Borderline Personality Disorder

In a study (DB-RCT) of 54 borderline personality patients, phenelzine decreased depression and irritability while increasing excitement and reactivity [R].

Phenelzine was tested against imipiramine and a placebo. It demonstrated the highest percentage of improvement in the symptoms of 60 patients (DB-RCT) who have atypical depression and borderline personality disorder [R].

4) Phenelzine Treats PTSD

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

Phenelzine significantly reduced sleep disturbance in combat veterans [R].

In a study (DB-RCT) 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 [R].

5) Phenelzine Treats Mutism

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

It also cured selective mutism in four children, ages 5 ½ to 7. There was no recurrence of mutism after discontinuing phenelzine use [R].

6) Phenelzine 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 [R].

7) Phenelzine Treats Bulimia

In a study (DB-RCT) of 50 bulimic patients, phenelzine decreased binge eating frequency. However, its side effects caused some patients to discontinue phenelzine use [R].

It also decreased bulimic and depressive symptoms in another 24 person study (DB-RCT) [R].

8) Phenelzine May Decrease Nicotine Dependence

In a study of rats, phenelzine decreased dependence of high doses of nicotine [R].

9) Phenelzine May Increase Pain Resistance

In mice, injections (either by itself or in combination with amitriptyline) increased tolerance to pain. The mice injected with phenelzine were more tolerant to pain than mice injected with salt water for up to 24 hours [R].

10) Phenelzine May Treat OCD

In a study (DB-RCT) of 30 OCD patients, phenelzine decreased obsessive-compulsive and depressive symptoms [R].

11) Phenelzine May Relieve Chronic Diarrhea

Phenelzine cured a patient of chronic (36-year lasting) diarrhea and underlying depression [R].

Side Effects of Nardil

Phenelzine can be addictive [R].

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

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

Common Side Effects of Phenelzine

Common side effects include [R, R, R, R]:

  • 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

Phenelzine Reduces Blood Levels of Vitamin B6

In a study of 19 patients who took phenelzine, their vitamin B6 blood levels were reduced by an average of 54% compared to the control group [R].

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

Phenelzine May Cause Heart Failure

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

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 [R].

Phenelzine May Cause Low Blood Sugar

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

Phenelzine Can Damage Mental Health

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

Phenelzine is also associated with increased hostility [R].

Limitations and Caveats

Many of Phenelzine’s benefits have yet to be investigated outside of animal studies.

Though these studies point in the direction of benefit, it is still advised to be cautious when using and supplementing the drug. All MAOIs should be obtained through prescription, and only after consulting a physician on your possible need for the medication.

Drug Interactions

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

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 [R, R].

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

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

Other Interactions

Phenelzine may increase blood pressure when coupled with intravenous, or oral, intake of tyramine [R].

Beers on tap may contain high tyramine levels and should not be consumed while taking phenelzine as it could result in hypertensive episodes [R].

Surprisingly, phenelzine may cause hypertensive crises when taken with cheese. Cheese has been found to also be high in tyramine [R].

When phenelzine is taken with ginseng, the resulting side effects may include sleeplessness, nervousness, hypertension, euphoria, and headaches [R].

Dosage

Dosages for phenelzine/Nardil often vary depending on its use:

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

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

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 [R].

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

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

User Reviews

Users commented that Nardil improved their anxiety, depression, and PTSD. It also helped with their social phobias. Phenelzine was effective in treating their symptoms when many other drugs did not work.

However, one user noted that Nardil caused him to gain over 50 pounds, and have sexual dysfunction after 4 years of use.

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

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The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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2 COMMENTS

  • J Wolf

    I take it you were paid well to push this drug that has long fallen out of favor because of serious ‘side effects.’

    1. Caroline Lam

      Hi, we only try to provide information based on peer-reviewed scientific articles available on PubMed. In fact, we have many drug posts, which all have a disclaimer saying we aren’t advocating for its use, only providing information. Hope that helps!

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