Phenelzine is only approved for the treatment of major depressive disorder (MDD) but has a wide range of applications. It is used “off-label” to improve social phobias, alleviate depression, and treat various addictions. Read on to learn more about how phenelzine works, what it is used for, and its side effects.

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 [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 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 [R].

MAO inhibitors, such as phenelzine, are also capable of 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 the livers of rats [R, R].

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 [R, R].

Uses of Phenelzine

1) Improves 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 [R].

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

A study 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) 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 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) May Help Improve Borderline Personality Disorder

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

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 [R].

4) Helps 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 [R].

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

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 [R].

5) May Improve 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 5½ to 7. There was no recurrence of mutism after discontinuing phenelzine use [R].

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 [R].

7) May Improve Bulimia

In a study 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 [R].

8) May Improve OCD

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

Side Effects and Precautions

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

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

Less Common Side Effects

1) 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].

2) 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].

3) Phenelzine 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) [R].

4) 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].

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 often vary depending on its use:

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

For the 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].

Limitations and Caveats

Many of phenelzine’s benefits have yet to be investigated outside of animal studies. Therefore caution should always be used when using phenelzine for anything other than what it was approved to treat (major depressive disorder – MDD). All MAOIs should be obtained through prescription, and only after consulting with a qualified healthcare provider.

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