Reviewed on 5/5/2022

What Is Phenelzine and How Does It Work?

Phenelzine is a prescription medicine used to treat the symptoms of depression.

  • Phenelzine is available under the following different brand names: Nardil

What Are Dosages of Phenelzine?

Adult dosage


  • 15mg


Adult and geriatric dosage

  • Initial 15 mg orally every 8 hours, increase not to exceed 20-30 mg every 8 hours
  • Dosage should be increased to at least 60 mg/day at a fairly rapid pace consistent with patient tolerance; may be necessary to increase dosage up to 90 mg/day to obtain sufficient MAO inhibition; many patients do not show a clinical response until treatment at 60 mg has been continued for at least 4 weeks
  • After maximum benefit from the drug is achieved, decrease the dose after the maximum response (2-6 weeks) over a 2-6 week period to maintain a dose as low as 15 mg once daily or every other day

Dosage Considerations – Should be Given as Follows: 

  • See “Dosages”

What Are Side Effects Associated with Using Phenelzine?

Common side effects of Phenelzine include:

  • dizziness,
  • drowsiness,
  • weakness,
  • sleep problems (insomnia),
  • constipation,
  • upset stomach,
  • dry mouth,
  • decreased urination,
  • impotence, and
  • difficulty having an orgasm.

Serious side effects of Phenelzine include:

  • hives,
  • difficulty breathing,
  • swelling of face, lips, tongue, or throat,
  • mood changes,
  • anxiety,
  • panic attacks,
  • trouble sleeping,
  • impulsive behavior,
  • irritableness,
  • agitation,
  • hostility,
  • aggression,
  • restlessness,
  • hyperactivity (mentally or physically),
  • increased depression,
  • suicidal thoughts,
  • sudden and severe headache,
  • rapid heartbeat,
  • stiffness in the neck,
  • nausea,
  • vomiting,
  • cold sweat,
  • sweating,
  • vision problems,
  • sensitivity to light,
  • chest pain,
  • fast or slow heart rate,
  • swelling,
  • rapid weight gain,
  • unusual thoughts or behavior,
  • lightheadedness, and
  • fainting.

Rare side effects of Phenelzine include:

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Other Drugs Interact with Phenelzine?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

  • Phenelzine has severe interactions with at least 90 other drugs.
  • Phenelzine has serious interactions with at least 81 other drugs.
  • Phenelzine has moderate interactions with at least 87 other drugs.
  • Phenelzine has minor interactions with the following drugs: 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

What Are Warnings and Precautions for Phenelzine?


Effects of drug abuse

  • None

Short-Term Effects

  • See “What Are Side Effects Associated with Using Phenelzine?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Phenelzine?”


  • Orthostatic hypotension may occur
  • Hypertensive reactions may occur from the consumption of foods high in tyramine or supplements containing caffeine, tyrosine, tryptophan, phenylalanine, or phenylalanine
  • Not first-line therapy
  • Discontinue 10 days before surgery
  • Therapy is not approved for treating any indications in the pediatric population
  • Most serious reactions involve changes in blood pressure
  • Therapy may cause excessive stimulation in schizophrenic patients
  • Drug potentiates hexobarbital hypnosis in animals; barbiturates should be given at a reduced dose with phenelzine
  • Drugs should be used with caution in diabetes mellitus; increased insulin sensitivity may occur; requirements for insulin or oral hypoglycemics may be decreased; there is conflicting evidence as to whether or not MAO inhibitors affect glucose metabolism or potentiate hypoglycemic agents; this should be kept in mind if the drug is administered to diabetics
  • Hypertensive crises
    • The most important reaction associated with therapy is the occurrence of hypertensive crises, which have sometimes been fatal
    • The crises are characterized by the occipital headache which may radiate frontally, palpitation, neck stiffness or soreness, nausea, vomiting, sweating (sometimes with fever and sometimes with cold, clammy skin), dilated pupils, and photophobia; either tachycardia or bradycardia may be present and can be associated with constricting chest pain
    • Intracranial bleeding has been reported in association with an increase in blood pressure; blood pressure should be observed frequently to detect evidence of any pressor response in all patients receiving therapy; therapy should be discontinued immediately upon the occurrence of palpitation or frequent headaches during therapy
    • If a hypertensive crisis occurs, the drug should be discontinued immediately and therapy to lower blood pressure should be instituted immediately; based on present evidence, phentolamine is recommended; the dosage reported for phentolamine is 5 mg intravenously; care should be taken to administer this drug slowly to avoid producing an excessive hypotensive effect; fever should be managed using external cooling
  • Suicide risk
    • 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, and this risk may persist until significant remission occurs
    • Unknown whether the suicidality risk extends to longer-term use, ie, beyond several months; however, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression
    • All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decrease
    • The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric; although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality
    • Consider changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms
    • Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior; monitoring should include daily observation by families and caregivers; prescriptions should be written for the smallest quantity of tablets consistent with good patient management, to reduce risk of overdose
  • Bipolar disorder
    • A major depressive episode may be the initial presentation of bipolar disorder; it is generally believed that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder; whether any of the symptoms of depression described representing such a conversion is unknown
    • Of the more severe side effects reported with any consistency, hypomania has been the most common; this reaction has been largely limited to patients in whom disorders characterized by hyperkinetic symptoms coexist, but are obscured by, depressive effect; hypomania usually appeared as depression improved; if agitation is present, maybe increased with therapy; hypomania and agitation have also been reported at higher than recommended doses or following long-term therapy
    • Before initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression; therapy is not approved to treat bipolar depression
  • Drug interaction overview
    • In patients receiving nonselective monoamine oxidase (MAO) inhibitors in combination with serotoninergic agents, there have been reports of serious, sometimes fatal, reactions; phenelzine should not be used concomitantly with a serotoninergic agent
    • Administration of guanethidine to patients receiving an MAO inhibitor can produce moderate to severe hypertension due to the release of catecholamines; at least two weeks should elapse between the withdrawal of the MAO inhibitor and initiation of guanethidine

Pregnancy and Lactation

  • Use with caution if benefits outweigh risks during pregnancy/
  • Lactation
    • unknown; use caution
Medscape. Phenelzine.

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