Section 3.2.3

Monamine Oxidase Inhibitors (MAOIS)

General Description

The monamine oxidase inhibitors (MAOIs) are probably as effective and safe as the tricyclic antidepressants, provided reasonable dietary precautions are followed. These dietary precautions were not fully understood when the drugs were initially introduced, resulting in hypertensive crises and fatalities.

The two most common MAOIs in the United States are phenelzine (Nardil) and tranylcypromine (Parnate). There is also a new class of MAOIs called RIMAs, which are currently under development and may be introduced to the market in the near future.

The RIMA classes of MAOIs have reversible binding. These new RIMA medications require 2-5 days to pass before tyramine-containing foodstuffs can safely be ingested. The two likely RIMAs to reach the U.S. markets are moclobemide and brofaromine.

Indications for Medication

The indications for MAOIs are similar to those for tricyclic and tetracyclic antidepressants. MAOIs may be particularly effective in agoraphobia with panic attacks, post-traumatic stress disorder, eating disorders, social phobia and pain syndromes.

Some research data indicates that MAOIs may be preferable to tricyclic antidepressants in the treatment of atypical depressions that are characterized by hypersomnia, hyperphagia, anxiety and the absence of major vegetative symptoms.

Clinical Guidelines

There is no definitive rationale for choosing one MAOIs over another. Tranylcypromine may be the most activating of these drugs.

Phenelzine should be started with a test dose of 15mg on the first day. The dosage should be increased gradually to 45mg a day after the first week and possibly to 90mg a day after the fourth week.

Tranylcypromine should be started with a test dose of 10mg on the first day. The dosage should be increased gradually to 30mg a day after the first week and possibly to 40-60mg a day after the fourth week.

If the trial of a MOAI is unsuccessful after six weeks, lithium or L-triodothyronine may be warranted for augmentation. In some cases MAOIs can be combined with tricyclic antidepressants.

Adverse Effects

The most frequent adverse effects of MAOIs are orthostatic hypotension, weight gain, edema, sexual dysfunction and insomnia. Weight gain, edema and sexual dysfunction are often not responsive to any treatment and often create problems with treatment compliance.

Patients with weight gain, edema and sexual dysfunction should probably be switched from a hydrazine (phenelzine) to a nonhydrazine (tranylcypromine) or vice versa. When switching from one MAOI to another, the clinician should taper and stop the first MAOI and wait for 14 days before starting the second MAOI.

There are uncommon reports that hydrazine MAOIs are associated with hepatotoxic effects. MAOIs are less cardiotoxic and less epileptogenic than the tricyclic or tetracyclic antidepressants. Still, MAOIs should be used with caution in patients with renal disease, seizure disorders, cardiovascular disease or hyperthyroidism.

MAOIs may exacerbate symptoms of Parkinson's Disease or alter the hypoglycemic agent in diabetic patients. MAOIs may provoke a manic episode in bipolar disorder or exacerbate psychosis in patients with schizophrenia.

MAOIs are contraindicated during pregnancy. MAOIs pass into breast milk and are contraindicated for nursing mothers.

The most significant adverse reaction to the MAOIs is the tyramine-induced hypertensive crisis which can be life threatening. Patients should be warned about the ingestion of tyramine-rich foods while taking MAOIs, and should be advised to continue the dietary restrictions for two weeks after stopping MAOIs.

The prodromal symptoms of a hypertensive crisis may include headache, stiff neck, sweating, nausea and vomiting. If those symptoms occur, patients should seek immediate medical attention. A MAOI-induced hypertensive crisis can be treated with nifedipine (procardia). However, this treatment is potentially hazardous because it can produce such a rapid drop in blood pressure.

Drug-Drug Interactions

The inhibition of MAOIs can cause severe and fatal interactions with various drugs. Patients should be instructed to tell any other physicians who are treating them that they are taking a MAOI.

The drugs which must be avoided while taking an MAOI include any of the following: anesthetic involving epinephrine, antiasthmatic medication, some antihypertensives, diuretics, L-Dopa, SSRI's, Effexor, Serzone, narcotics, over-the counter cold, hay fever and sinus drugs (especially those containing dextromethorphan), and sympathomimetics.

A "cough" medication which may be safely used with a MAOI is plain Robitussin (guaifenesin), an expectorant.

The medications that must be used carefully while taking a MAOI include the following: antihistamines, disulfiram, hydralazine (Apresoline), propranolol (Inderal), terpin hydrate with codeine and tricyclic drugs.

The consent form for these medications is "Anti-depressant (MAOI's)".

Tyramine-Containing Foods1

Cheese/Dairy Products

American, processed

Blue

Boursault2

Brick, natural

Brie

Camembert2

Cheddar2

Emmenthaler2

Gruyere

Mozzarella

Parmesan

Romano

Roquefort

Sour cream

Stilton2

Yogurt

Meat/Fish

Beef or chicken liver,

Other meats, fish

(unrefrigerated,

fermented)

Meats prepared with

tenderizer

Fermented sausages

(bologna, pepperoni,

salami, summer

sausage)2

Game meat

Meat extracts

Caviar

Dried fish (salted

Herring)

Herring, pickled, spoiled2

Shrimp paste

Alcoholic Beverages (Undistilled)

Beer and ale (imports,

Some nonalcoholic)

Red wine (especially

Chianti)

Sherry

Fruit/Vegetables

Avocados (especially

overripe)

Yeast extracts

(Marmite, etc.)2

Bananas

Figs, canned (overripe)

Raisins

Sauerkraut

Soy sauce

Miso soup

Bean curd

Foods Containing Other Vasopressors

Fava beans (overripe)

- dopamine

Caffeine (e.g., coffee, tea, colas)

Chocolate ?

Phenylethylamine

Ginseng

1 Tyramine contents are not predictable and may vary. The amounts of tyramine are estimated from low to very high.

2 Contains high to very high amounts of tyramine.

MAOI Drug Interactions

Precipitant Drug

Object Drug


Description

Methylphenidate

MAOI's

Inc.

Coadministration may cause a hypertensive crisis.

Metrizamide

MAOI's

Inc.

Discontinue MAOI's at least 48 hours before myelography and do not resume for at least 24 hours post-procedure because of the decrease of the seizure threshold

MAOI's

Anesthetics

Inc.

Patients taking MAOI's should not undergo elective surgery requiring general anesthesia. Do not give cocaine or local anesthesia containing sympathomimetic vasoconstrictors. Keep in mind the possible combined hypotensive effects of MAOI's and spinal anesthesia. Discontinue the MAOI at least 10 days before elective surgery

MAOI's

Antidepressants

Inc.

Do not administer MAOI's together with or immediately following these agents. There have been reports of serious, sometimes fatal, reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible fluctuations of vital signs, and mental status changes that include extreeme agitationand confusion progressing to delerium and coma). Do not administer MAOI's together or in rapid succession with other MAOI's.

MAOI's

Antidiabetic agents

Inc.

MAOI's may potentiate the hypoglycemic response to insulin or sulfonyureas and delay recovery from hypoglycemia.

MAOI's

Barbiturates

Inc.

Give barbiturates at a reduced dose with MAOI's

MAOI's

Beta Blockers

Inc.

Bradycardia may develop during concurrent use of certain MAOI's and beta blockers.

MAOI's

Bupropion

Inc.

The concurrent use of an MAOI and bupropion HCl is contraindicated. Allow at least 14 days between discontinuation of an MAOI and initiation of bupropion HCl treatment.

MAOI's

Buspirone

Inc.

Do not take isocarboxazid in combination with buspirone. Several cases of elevated blood pressure have occurred. Allow at least 10 days between discontinuation of isocarboxazid and institution of buspirone.

MAOI's

Carbamazepine

Inc.

Hypertensive crises, severe convulsive seizures, coma, or circulatory collapse may occur in patients receiving such combinations.

MAOI's

Cyclobenzaprine

Inc.

Because cyclobenzaprine is structurally related to the tricyclic antidepressants, use with caution with MAOI's.

MAOI's

Dextromethorphan

Inc.

Hyperpyrexia, abnormal muscle movement, psychosis, bizarre behavior, hypotension, coma and death have been associated with this combination.

MAOI's

Guanethedine

Dec.

MAOI's may inhibit the hypotensive effects of guanethedine.

MAOI's

Levodopa

Inc.

Hypertensive reactions occur if levodopa is given to patients receiving MAOI's.

MAOI's

Meperidine

Inc.

Coadministration or use within 2-3 weeks of one another may result in agitation, seizures, diaphoresis, and fever, progress to coma, apnea, and death. Adverse reactions are possible weeks after MAOI withdrawal. Avoid this combination; administer other narcotic analgesics with caution.

MAOI's

Methyldopa

Inc.

Coadministration may cause loss of blood pressure control or signs of central stimulation (e.g. excitation, hallucinations).

MAOI's

Rauwolfia alkaloids

Inc.

MAOI's inhihit the destruction of serotonin and norepinephrine, which are believed to be released from tissue stores by rauwolfia alkaloids. Exercise caution when rauwolfia is used concommittantly with MAOI's.

MAOI's

Sulfonamide

Inc.

Coadministration may cause sulfonamide or MAOI toxicity

Sulfonamide

MAOI's

Inc.


MAOI's

Sumatriptan

Inc.

Systemic exposure to sumatriptan may be increased, producing toxicity.

MAOI's

Sympathomimetics

Inc.

The MAOI's potentiation of indirect or mixed-acting sympathominetic substances, including anorexiants, may result in severe headache, hypertension, high fever, and hyperpyrexia, possibly resulting in hypertensive crisis; avoid coadministration.

MAOI's

Thiazide diuretics

Inc.

Exaggerated hypotensive effects may result from concurrent use.

MAOI's

L-Tryptophan

Inc.

Coadministration may result in hyperreflexia, confusion, disorientation, shivering, myoclonic jerks, agitation, amnesia, delirium, hypomanic signs, ataxia, ocular oscillations, Babinski signs.

Inc. = Object drug increased
Dec. = Object drug decreased

Reference: Facts and Comparisons Jan. 2000