Phenelzine

Prescription ·Exploratory record · not publication-reviewed ·Updated July 13, 2026

Phenelzine is an irreversible nonselective MAOI used for depression, especially atypical or treatment-resistant depression when other antidepressants are inadequate. It can be highly effective but requires strict attention to tyramine-restricted diet, drug washouts, blood pressure, and serotonin-syndrome risk. Because it is a hydrazine MAOI, functional vitamin B6 depletion and neuropathy are clinically relevant safety issues.

Read the sources → Compare profiles

Publication status

Exploratory record, not a reviewed medical publication.

See the editorial and medical-review policies for the publication gate.

This generated database record has not completed a claim-level review by a qualified human medical reviewer. Bibliography links and evidence labels are not approval. The page remains available for reference and is excluded from search indexing.

In short

What the research says.

A quick, data-only summary. The full evidence, dosing, and sources are below.

Phenelzine is an irreversible nonselective MAOI used for depression, especially atypical or treatment-resistant depression when other antidepressants are inadequate. NutriStack rates the supporting evidence as strong. Common adult dosing is Commonly start 15 mg three times daily and titrate to 60 mg/day; some patients require up to 90 mg/day. Maintenance dosing is individualized and should use the lowest effective dose., though a prescriber sets the actual dose. With long-term use it can deplete vitamin b6. This profile indexes 3 sources.

What it's good for

Treatment-resistant major depressive disorder
Atypical depression with hypersomnia or rejection sensitivity
Some anxiety-spectrum symptoms when prescribed by specialists²

What to watch for

Orthostatic hypotension
Weight gain
Edema
Hypersensitivity to phenelzine^2,3
Pheochromocytoma

The bottom line

Evidence rating strong. Most-documented uses: treatment-resistant major depressive disorder, atypical depression with hypersomnia or rejection sensitivity, some anxiety-spectrum symptoms when prescribed by specialists. 3 sources indexed (1994–2018), with 0 interaction records on file.

The science

How it works, mechanistically.

Core mechanism

Phenelzine irreversibly inhibits monoamine oxidase A and B, reducing metabolism of serotonin, norepinephrine, dopamine, and dietary tyramine. Increased synaptic monoamines mediate antidepressant effects, while impaired tyramine metabolism can trigger abrupt norepinephrine release and hypertensive crisis. Phenelzine can also interfere with pyridoxal-5-phosphate metabolism, contributing to vitamin B6 depletion and neuropathy risk.^2,3

Class

Irreversible nonselective monoamine oxidase inhibitor antidepressant

Dosing

Dosing & protocol.

Common range

Commonly start 15 mg three times daily and titrate to 60 mg/day; some patients require up to 90 mg/day. Maintenance dosing is individualized and should use the lowest effective dose.

Recommended form

Oral tablet with specialist supervision and dietary counseling

May be taken with or without food. Patients must avoid high-tyramine foods and beverages during therapy and for 2 weeks after stopping.

Depletions

What it depletes.

Nutrients this medication can lower over time, and what to replace.

Vitamin B6

Moderate

Phenelzine is a hydrazine derivative that can bind or inactivate pyridoxal-5-phosphate, reducing active vitamin B6 availability and impairing B6-dependent neurotransmitter metabolism.

Replace Vitamin B6Monitor Plasma pyridoxal-5-phosphate and clinical monitoring for paresthesias or neuropathyOnset Weeks to months, especially with prolonged therapy, poor intake, or neuropathy symptoms

Full Phenelzine depletion and interaction guide →

Safety

Full safety detail.

Side effects

Orthostatic hypotension
Weight gain
Edema
Dry mouth
Constipation
Sexual dysfunction
Insomnia or sedation
Hypertensive crisis with tyramine or sympathomimetics
Serotonin syndrome with serotonergic agents
Hepatotoxicity
Vitamin B6-related peripheral neuropathy

Contraindications

Hypersensitivity to phenelzine^2,3
Pheochromocytoma
Congestive heart failure
History of liver disease or abnormal liver function tests
Severe renal impairment
Cerebrovascular disease
Concomitant MAOIs, serotonergic antidepressants, serotonin precursors, meperidine, tramadol, methadone, dextromethorphan, sympathomimetics, or St. John's Wort^1,2
Inability to follow tyramine-restricted diet or medication washout requirements^1,3

Sources

Sources, by evidence tier.

Numbered references. Citations throughout the page link here.

Reviews & position papers

1The prescriber's guide to the MAOI diet - thinking through tyramine troublesGillman PK · Journal of Neural Transmission · 2018
Review discusses tyramine mechanisms and practical risk mitigation for MAOI prescribing.

Observational studies

2Phenelzine-induced pyridoxine deficiencyMalcolm DE et al. · Clinical Neuropharmacology · 1994
Clinical reports link phenelzine exposure with pyridoxine deficiency and neuropathic symptoms.

Reference material

3PHENELZINE SULFATE tablets, US Prescribing InformationURLU.S. National Library of Medicine · DailyMed · 2017
Labeling describes MAOI indications, contraindications, hypertensive crisis risk, and tyramine food restrictions.

FAQ

Common questions.

Quick answers about Phenelzine, drawn from the data on this page.

What is Phenelzine?

What is Phenelzine used for?

Commonly cited benefits of Phenelzine include: Treatment-resistant major depressive disorder; Atypical depression with hypersomnia or rejection sensitivity; Some anxiety-spectrum symptoms when prescribed by specialists. NutriStack rates the overall evidence as strong.

What is a typical dose of Phenelzine?

A typical adult dose of Phenelzine is Commonly start 15 mg three times daily and titrate to 60 mg/day; some patients require up to 90 mg/day. Maintenance dosing is individualized and should use the lowest effective dose.. The commonly recommended form is Oral tablet with specialist supervision and dietary counseling. These are general ranges, not personalized advice; confirm the right dose with a clinician.

What are the side effects of Phenelzine?

Reported side effects include orthostatic hypotension, weight gain, edema, dry mouth, constipation, sexual dysfunction. This is educational information; check with a healthcare professional before use.

How strong is the evidence for Phenelzine?

NutriStack rates this as Strong, meaning multiple high-quality meta-analyses or systematic reviews converge on the same finding. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.

Use this with your stack

Phenelzine in NutriStack.

Add it to your stack, see how it interacts with everything else you take, and get a Stack Score that updates the moment it does.

Download on the App Store → Read the methodology