Phenelzine

Mechanism-of-action class: Monoamine Oxidase Inhibitors.

• Phenelzine Sulfate Tablets, USP has been found to be effective in depressed patients clinically characterized as "atypical," "nonendogenous," or "neurotic." These patients often have mixed anxiety and depression and phobic or hypochondriacal features. There is less conclusive evidence of its usefulness with severely depressed patients with endogenous features.

• Phenelzine Sulfate Tablets should not be used in patients who are hypersensitive to the drug or its ingredients, with pheochromocytoma, congestive heart failure, severe renal impairment or renal disease, a history of liver disease, or abnormal liver function tests. The potentiation of sympathomimetic substances and related compounds by MAO inhibitors may result in hypertensive crises (see WARNINGS ).contraindicated

Initial dose The usual starting dose of Phenelzine Sulfate Tablets is one tablet (15 mg) three times a day. Early phase treatment Dosage should be increased to at least 60 mg per day at a fairly rapid pace consistent with patient tolerance. It may be necessary to increase dosage up to 90 mg per 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. Maintenance dose After maximum benefit from Phenelzine Sulfate Tablets is achieved, dosage should be reduced slowly over several weeks. Maintenance dose may be as low as one tablet, 15 mg, a day or every other day, and should be continued for as long as is required.

Clinical Worsening and 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. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18–24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients.

Phenelzine Sulfate Tablets is a potent inhibitor of monoamine oxidase. Because this enzyme is widely distributed throughout the body, diverse pharmacologic effects can be expected to occur. When they occur, such effects tend to be mild or moderate in severity (see below), often subside as treatment continues, and can be minimized by adjusting dosage; rarely is it necessary to institute counteracting measures or to discontinue Phenelzine Sulfate Tablets. Common side effects include: Nervous System —Dizziness, headache, drowsiness, sleep disturbances (including insomnia and hypersomnia), fatigue, weakness, tremors, twitching, myoclonic movements, hyperreflexia. Gastrointestinal —Constipation, dry mouth, gastrointestinal disturbances, elevated serum transaminases (without accompanying signs and symptoms). Metabolic —Weight gain. Cardiovascular —Postural hypotension, edema. Genitourinary —Sexual disturbances, eg, anorgasmia and ejaculatory disturbances and impotence. Less common mild to moderate side effects (some of which have been reported in a single patient or by a single physician) include: Nervous System —Jitteriness, palilalia, euphoria, nystagmus, paresthesias. Genitourinary —Urinary retention. Metabolic —Hypernatremia. Dermatologic —Pruritus, skin rash, sweating. Special Senses —Blurred vision, angle-closure glaucoma.

Metabolism

Absorption Following a single 30 mg dose of Phenelzine Sulfate Tablets (2 × 15 mg tablets), a mean peak plasma concentration (C max ) of 19.8 ng/mL occurred at a time (T max ) of 43 minutes postdose. Metabolism Phenelzine Sulfate Tablets is extensively metabolized, primarily by oxidation via monoamine oxidase.

Note —For management of hypertensive crises see WARNINGS section. Accidental or intentional overdosage may be more common in patients who are depressed. It should be remembered that multiple drugs and/or alcohol may have been ingested. Depending on the amount of overdosage with Phenelzine Sulfate Tablets, a varying and mixed clinical picture may develop, including signs and symptoms of central nervous system and cardiovascular stimulation and/or depression. Signs and symptoms may be absent or minimal during the initial 12-hour period following ingestion and may develop slowly thereafter, reaching a maximum in 24–48 hours. Death has been reported following overdosage. Therefore, immediate hospitalization, with continuous patient observation and monitoring throughout this period, is essential.

• Jun 9, 1961NDANDA011909Parke Davis
• Dec 8, 2010ANDAANDA200181Novel Labs Inc

1. 1Drug Ineffective33021%
2. 2Depression18712%
3. 3Headache1378.8%
4. 4Anxiety1298.3%
5. 5Weight Increased1217.8%
6. 6Insomnia1046.7%
7. 7Drug Interaction1006.4%
8. 8Dizziness996.4%
9. 9Pharmaceutical Product Complaint976.2%
10. 10Fatigue946.0%
11. 11Feeling Abnormal895.7%
12. 12Malaise785.0%
13. 13Nausea774.9%
14. 14Hypertension764.9%
15. 15Fall613.9%

Recent PubMed references pinned to Phenelzine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Rapid Monoamine Oxidase Inhibitor Switches in Treatment-Resistant Depression: Safety Evaluation in 3 Cases.
  Journal of psychiatric practice · 2025 · Rached G, Fiani D, Campana AM, et al.
  PMID 40679804DOI 10.1097/PRA.0000000000000869
• An analog of phenelzine demonstrates effective acrolein scavenging and neuroprotection without monoamine oxidase inhibition in a rat SCI model.
  Neuroscience · 2025 · Sun S, Tian R, Alford A, et al.
  PMID 40189130DOI 10.1016/j.neuroscience.2025.04.005
• Identification of core genes, critical signaling pathways, and potential drugs for countering BPA-induced hippocampal neurotoxicity in male mice.
  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2023 · Lei X, Hao Z, Wang H, et al.
  PMID 37992956DOI 10.1016/j.fct.2023.114195
• Classics in Chemical Neuroscience: Selegiline, Isocarboxazid, Phenelzine, and Tranylcypromine.
  ACS chemical neuroscience · 2023 · Hoffman GR, Olson MG, Schoffstall AM, et al.
  PMID 37966854DOI 10.1021/acschemneuro.3c00591
• Phenelzine-based probes reveal Secernin-3 is involved in thermal nociception.
  Molecular and cellular neurosciences · 2023 · Bustin KA, Shishikura K, Chen I, et al.
  PMID 36924917DOI 10.1016/j.mcn.2023.103842
• The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression.
  CNS spectrums · 2023 · Van den Eynde V, Abdelmoemin WR, Abraham MM, et al.
  PMID 35837681DOI 10.1017/S1092852922000906
• Time to Reconsider Monoamine Oxidase Inhibitors for Obsessive Compulsive Disorder?: A Case Series Using Phenelzine.
  Journal of clinical psychopharmacology · 2021 · Grant JE, Baldwin DS, Chamberlain SR, et al.
  PMID 34108430DOI 10.1097/JCP.0000000000001418
• Overview of the Neuroprotective Effects of the MAO-Inhibiting Antidepressant Phenelzine.
  Cellular and molecular neurobiology · 2022 · Matveychuk D, MacKenzie EM, Kumpula D, et al.
  PMID 33839994DOI 10.1007/s10571-021-01078-3

The 10 most recently updated of 13 ClinicalTrials.gov registrations naming Phenelzine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Precision Care for Major Depressive Disorder
  Enrolling by invitation · Phase 4 · Interventional · 150 enrolled · University of California, San Francisco
  NCT06580041updated 2025-09-05
• Study to Evaluate the Pressor Effect of Oral Tyramine During Ozanimod Treatment in Healthy Adult Participants
  Completed · Phase 1 · Interventional · 128 enrolled · Celgene
  NCT04978298updated 2023-08-31
• Efficacy of Hydroxyzine for Patients With Panic Disorder
  Not yet recruiting · Phase 4 · Interventional · 80 enrolled · Sultan Qaboos University
  NCT05737511updated 2023-02-21
• Phenelzine Sulfate in Treating Patients With Non-metastatic Recurrent Prostate Cancer
  Completed · Phase 2 · Interventional · 26 enrolled · University of Southern California
  NCT02217709updated 2022-12-12
• A Study in Healthy People to Test How Combining BI 1467335 and Tyramine Affects Blood Pressure
  Terminated · Phase 1 · Interventional · 53 enrolled · Boehringer Ingelheim
  NCT03979820updated 2021-06-04
• An Early Phase Study of Abraxane Combined With Phenelzine Sulfate in Patients With Metastatic or Advanced Breast Cancer
  Completed · Phase 1 · Interventional · 8 enrolled · EpiAxis Therapeutics
  NCT03505528updated 2019-11-13
• Phenelzine Sulfate and Docetaxel in Treating Patients With Prostate Cancer With Progressive Disease After First-Line Therapy With Docetaxel
  Terminated · Phase 2 · Interventional · 11 enrolled · OHSU Knight Cancer Institute
  NCT01253642updated 2019-10-02
• Drug-drug Interaction Study of Ozanimod With Tyramine to Evaluate the Effect on Pressor Response
  Completed · Phase 1 · Interventional · 92 enrolled · Celgene
  NCT03694119updated 2019-07-19
• Neuroimaging MAO-B in Medication Free TR-MDD Using Novel Tracer
  Completed · Interventional · 8 enrolled · Centre for Addiction and Mental Health
  NCT02153281updated 2019-05-24
• A New Treatment Approach for Major Depressive Disorder Based Upon Targeting Monoamine Oxidase A (MAO-A)
  Completed · Early phase 1 · Interventional · 10 enrolled · Centre for Addiction and Mental Health
  NCT02269540updated 2019-05-24

Frequently asked questions

How does Phenelzine work?

Mechanism-of-action class: Monoamine Oxidase Inhibitors.

What is Phenelzine used for?

According to FDA labeling, Phenelzine carries indications including: Phenelzine Sulfate Tablets, USP has been found to be effective in depressed patients clinically characterized as "atypical," "nonendogenous," or "neurotic." These patients often have mixed anxiety and depression and phobic or hypochondriacal features. There is less conclusive evidence of its usefulness with severely depressed patients with endogenous features.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Phenelzine?

Phenelzine is classified as Monoamine oxidase inhibitors, non-selective, Monoamine Oxidase Inhibitor, Monoamine Oxidase Inhibitors, Increased Blood Pressure, Increased Dopamine Activity, Increased Norepinephrine Activity, Increased Serotonin Activity.

What are the brand names for Phenelzine?

Phenelzine is marketed under brand names including Nardil.

What are the contraindications for Phenelzine?

Phenelzine labeling lists contraindications including: Phenelzine Sulfate Tablets should not be used in patients who are hypersensitive to the drug or its ingredients, with pheochromocytoma, congestive heart failure, severe renal impairment or renal disease, a history of liver disease, or abnormal liver function tests. The potentiation of sympathomimetic substances and related compounds by MAO inhibitors may result in hypertensive crises (see WARNINGS ).. Always consult the full prescribing information and a clinician.