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Phenelzine Sulfate

Pronunciation: FEN-uhl-zeen SULL-fate
Class: MAOI

Trade Names

- Tablets 15 mg (as sulfate)


Phenelzine blocks activity of enzyme MAO, thereby increasing monoamine (eg, epinephrine, norepinephrine, serotonin) concentrations in CNS.

Slideshow: Depression, the Risk of Suicide, and Treatment Options



Phenelzine is well absorbed. T max is approximately 2 to 3 h.


Phenelzine metabolism is hepatic. It is metabolized with the release of active metabolites. Inactivation is mainly by acetylation.


Urine (mainly as metabolites).


As early as 7 to 10 days, may take up to 4 to 8 wk for full effect.


Up to 2 wk.

Indications and Usage

Treatment of “atypical” (“nonendogenous” or “neurotic”) depression; management of depression in patients unresponsive to other antidepressant drugs.

Unlabeled Uses

Treatment of bulimia; treatment of cocaine addiction; control of panic disorder with agoraphobia.


Hypersensitivity to MAOIs; pheochromocytoma; CHF; abnormal liver function; history of liver disease; severe renal function impairment; cerebrovascular defect; concurrent use of dextromethorphan or CNS depressants (eg, alcohol); sympathomimetic drugs (eg, amphetamine, dopamine, norepinephrine) or related drugs (eg, methyldopa); CV disease.

Dosage and Administration


PO 15 mg 3 times daily initially; may titrate up to 90 mg/day. Elderly should receive no more than 60 mg/day. After max benefit is achieved, dose can be slowly decreased over several weeks to maintenance dose. Doses as low as 15 mg every other day may be used for maintenance.

General Advice

  • Tablets may be crushed if patient is unable to swallow them whole.
  • Do not administer several days before surgery. If possible, discontinue 7 to 14 days before elective surgery.
  • Wait 14 days after discontinuing tricyclic antidepressants, other MAOIs, carbamazepine, maprotiline, guanethidine, paroxetine, sertraline cyclobenzaprine, or CNS stimulants to administer this medication. Wait 5 wk after discontinuing fluoxetine before starting phenelzine.


Store in tightly-closed container and protect from heat and light.

Drug Interactions

Amine-containing foods

May cause severe hypertension or hemorrhagic strokes.


May cause exaggerated pharmacologic effects (eg, severe headaches, hypertension, hyperpyrexia) of anorexiants (amphetamines and related compounds).

CNS depressants

May enhance CNS effects.


Concurrent use has been associated with severe reactions (eg, hyperpyrexia, hypotension, death).

Fluoxetine, paroxetine, sertraline, trazodone

Although data are limited, interactions comparable with those of the tricyclic antidepressants and phenelzine may occur.


MAOIs may antagonize the antihypertensive effect.

Insulin, sulfonylureas

May enhance hypoglycemic action.


May cause hypertensive reactions.


May lead to severe reactions, including hypotension, convulsions, respiratory depression, and vascular collapse.


May cause severe headache, hypertensive crisis, and hyperpyrexia.

Tricyclic antidepressants, buspirone, cyclobenzaprine, carbamazepine, maprotiline, guanethidine, CNS stimulants, tyramine

May lead to potentially fatal reactions, including seizures and hypertensive crisis; mental status changes, hyperthermia.

Laboratory Test Interactions

None well documented.

Adverse Reactions


Orthostatic hypotension; edema; hypertensive crisis.


Dizziness; headache; sleep disturbances; tremors; hyperflexemia; manic symptoms; convulsions; toxic delirium; coma.


Rash; sweating; photosensitivity.


Blurred vision; glaucoma.


Constipation; nausea; GI disturbances; anorexia.


Sexual dysfunction; urinary retention; incontinence.


Anemia; leukopenia; agranulocytosis; thrombocytopenia.


Fatal progressive necrotizing hepatocellular damage; elevated serum transaminases; hepatitis.


Weight gain; hypermetabolic syndrome (eg, fever, tachycardia, rapid breathing, rigidity, metabolism, acidosis, coma); hypernatremia.


Transient respiratory and circulatory depression following electroconvulsive therapy.



Category C .




Not recommended in patients younger than 16 yr of age.


Drug should be used cautiously in patients older than 60 yr of age because of possibility of existing cerebral sclerosis with damaged vessels. If hypertension develops, the risk of stroke may be increased.

Depression associated with drug abuse/alcoholism

Use with caution; increased risk of serious drug interactions.


May lower seizure threshold.


May alter glucose control.


Orthostatic hypotension is significant adverse reaction and may lead to falling and changes in heart rate.


Phenelzine may cause pyridoxine deficiency, with symptoms of numbness, paresthesias and edema. Supplements may be required.

Suicidal patients

Strict supervision may be necessary in patients at risk.



Excitement, hypotension, dizziness, movement disorders, irritability, insomnia, weakness, severe headache, anxiety, restlessness, drowsiness, coma, convulsions, flushing, hypertension, sweating, tachypnea, acidosis, hyperpyrexia, tachycardia, cardiorespiratory arrest, incoherence, agitation, mental confusion, shock.

Patient Information

  • Inform patient that it may be 4 wk before improvement in mood is noticed.
  • Instruct patient that antidepressant medications will not make him or her high or elevate mood; antidepressants restore depressed people to normal state.
  • Instruct patient to avoid sudden position changes to prevent orthostatic hypotension.
  • Instruct patient that it is important to consult health care provider before taking any medication and that it is especially important to avoid OTC cold, hay fever, or weight reduction preparations.
  • Instruct patient to avoid tyramine- or tryptophan-containing foods while taking drug and for 2 wk after discontinuing medication. These are protein foods that are aged or fermented and include cheeses, pickled herring, liver, hard sausage (eg, Genoa salami or pepperoni), pods of broad beans, beer, red wine, yeast extract, yogurt, ginseng, soy sauce, bananas, raisins, and avocados. Advise patient to consult dietitian.
  • Instruct patient to ingest caffeine and chocolate in moderation.
  • Advise patient to weigh self 2 to 3 times/wk and report unusual gains.
  • Instruct patient to stop taking phenelzine and to notify health care provider immediately if severe headache, severe chest pain, change in heart rate, photophobia, increased sweating, nausea and vomiting, or stiff or sore neck occurs.
  • Advise patient not to use alcohol or any abuse drug.
  • Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.

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