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A Review of Monoamine Oxidase Inhibitors PsyComNet 27 May 1993 - Ivan Goldberg, MD

I. History
Monoamine oxidase inhibitors were among the first drugs utilized by modern psychopharmacologists. In the late 1950s the New York Times ran a picture of patients whose tuberculosis was controlled with iproniazid (an antitubercular drug with MAOI activity) dancing in their ward. A number of psychiatrists viewing that picture considered the possibility that the patients were dancing, not because of their joy about having their tuberculosis controlled, but rather because hypomania had been induced by the iproniazid. After a brief spurt of interest in MAOIs as antidepressants, they fell into a period of relative disuse. Fear of unexpected hypertensive episodes and questions of efficacy lead to many psychiatrists abandoning their use until the mid-1970s.

II. Mechanism of action
MAOIs inhibit monoamine oxidase (MAO) in the brain. As MAO catabolizes serotonin, norepinephrine, and dopamine, treatment with an MAOI leads to increased amounts of these neurotransmitters.

III. Indications
A. Atypical depression: i.e., a depression characterized by non-autonomous depression, high levels of anxiety, great lethargy when depressed, overeating and oversleeping.

B. Hysteroid dysphoria (a subtype of atypical depression): i.e., a depression in patients who are characterized by flamboyance, seductiveness, marked vulnerability to personal rejection with dramatic crashes in mood. Such patients often report extreme lethargy when depressed (leaden paralysis), retreating to bed, and oversleeping and often overeating. The depression is often reversible if the patient receives positive social input from a new boyfriend for example.

C. Bulimia: an eating disorder which many psychiatrists is closely related to depression, frequently responds to treatment with MAOIs.

D. Depression in the elderly. Excessive levels of monoamine oxidase activity have been demonstrated in depressed geriatric patients. Many such patients do very well when treated with MAOIs.

E. Panic disorder. While panic attacks can be controlled by the use of benzodiazepines such as Xanax, and by tricyclic antidepressants such as Tofranil, many psychiatrists consider MAOIs to be the drugs of choice in blocking panic attacks in patients with severe Panic Disorder.

F. Social phobias. Individuals with phobias regarding eating, writing or appearing in public often respond better to MAOIs than to other psychopharmacologic agents.

IV. Dosing
A. Despite the doses listed in PDR, adults usually require a daily dose of at least 1 mg/Kg. of Parnate, Nardil or Marplan.. Pediatric doses are usually stated as 0.3 to 1 mg/Kg, but larger doses may be necessary.

V. Duration of treatment
As relapse of depression is common in the first two years after an index episode, it is often suggested that patients remain on MAOIs for at least two years. Patients who have had three or more episodes of depression are candidates for lifetime prophylactic medication. Lithium or MAOIs may be employed for long-term therapy.

VI. Laboratory monitoring of MAOI therapy

A. Routine tests to detect adverse effects on the bone marrow,liver etc CBC, Chemscreen and urine analysis should be obtained every 6 months.

B. Measurements of platelet MAO activity. Platelet MAO activity has been shown to be highly correlated with MAO activity in the brain. by measuring the degree of inhibition of platelet MAO one may titrate the dose of an MAOI. MAOIs are maximally effective only when there is an 80% or greater inhibition of platelet MAO

VII. Adverse Effects - With incidence over 10%
Anorgasmia Blurred vision Drowsiness/sedation Excitement/hypomania Headache Insomnia Nausea Orthostatic hypotension (While hypertension Tachycardia is feared, hypo- Weight Gain tension is a greater problem for many more patients.) The adverse effects that most frequently lead patients to prematurely discontinue MAOI therapy are: Anorgasmia Edema Hypomania Insomnia Orthostatic hypotension Weight gain

VIII. Drug-Food Interactions
The fermentation of protein liberates tyramine, an amino acid that has indirect sympathomimetic effects. Among some of the foods highest in tyramine are: Aged cheeses (e.g. blue, cheddar, Parmesan, Stilton, Swiss) Pickled herring, pickles, sauerkraut. Aged sausages such as hard salami, bologna, mortadella, pepperoni Sour cream Overripe fruit, especially bananas and avocados Red wine, beer, sherry, liqueurs Caviar, escargot, anchovies If a food high in tyramine is ingested the patient may experience a hypertensive episode characterized by a severe occipital headache, stiff neck, nausea, vomiting, constricting chest pain, dilated pupils, and tachycardia. Patients may be prescribed Nifedipine 10 mg capsules and instructed that if they experience the symptoms of a hypertensive episode that they should bite into a capsule and immediate swallow it. They should also head for a hospital E.R. where more definitive treatment is available.

IX. Drug-Drug Interactions
Amipaque - Potentiation of seizure-inducing properties (used in myelography). Alcohol, barbiturates, anesthetics - increased CNS depression. Anti-cholinergics - increased atropine-like effects. Buspar - hypertension reported Demerol - Absolutely contraindicated. Demerol is responsible for more deaths in patients taking MAOI than all other drugs combined. Narcotics - Codeine or morphine may be used. As potentiation is possible start by reducing usual dose by 50%. Titrate dose according to patient's response. Over-the-counter drugs to be avoided are: Cold remedies containing decongestants Appetite suppressants such as Dexatrim Anti-asthma drugs such as Primatine Cough medications containing dextro- methorphan. Prozac and other selective serotonin reuptake blockers such as Zoloft and Paxil may cause a fatal serotonin syndrome characterized by CNS irritability, increased muscle tone, myoclonus, diaphoresis, and hyperpyrexia. Succinylcholine - Prolonged apnea a possibility Sympathomimetics Indirect: such as: amphetamine, methyl- phenidate, ephedrine, pseudoephedrine, phenyl- propanolamine, dopamine, tyramine are DRAMATICALLY potentiated. Direct: such as epinephrine, isoproterenol, norepinephrine, and methoxamine are less dramatically potentiated but should be avoided except in emergency situations. Tricyclic antidepressants - Dangerous if started while a patient is on an MAOI but safe if started with the MAOI or if the MAOI is started after the tricyclic drug has been started.

X. Overdose
A syndrome characterized by insomnia, restlessness, anxiety and at times agitation has been reported in patients taking an overdose. Mental confusion, and incoherence may be seen. While hypertension is possible, hypotension is seen more often. Hyperpyrexia may be severe and should be treated with external cooling.

XI. Use in Pregnancy and lactation
A. Use in Pregnancy The safety of MAOIs in pregnancy is unknown. B. Use in nursing mothers The American Academy of Pediatrics considers Parnate therapy to be compatible with breast feeding even though small amounts of the drug are found in breast milk

XII. Future developments
A reversible inhibitor of monoamine oxidase (RIMAO) has been developed. This drug. moclobemide, will make MAOI therapy easier as there are no food restrictions as long as the drug is taken at the end of meals and no foods high in tyramine are eaten for the next 3-4 hours. Moclobemide has many fewer side effects than the conventional MAOI. Insomnia, the most common side effect, is reported by less than 10% of those who have been treated to date. This drug seems to be especially useful for the treatment of long- standing mild depressions (dysthymia) that do not respond to other antidepressan