Monday, February 1, 2010

MAOIs


The old class of antidepressants known as monoamine oxidase inhibitors are used in the treatment of smoking cessation as well as atypical and treatment resistant depression. They are also used for treating social anxiety, agoraphobia, panic disorder and borderline personality disorder.

The neurotransmitters serotonin, norepinephrine and dopamine are monoamines. In the gap between nerve cells - the synapse - used neurotransmitters are destroyed by an The enzyme called monoamine oxidase (MAO) degrades these neurotransmitters. And depression is associated with low levels of the neurotransmitters. MAOIs block the activity of this enzyme, increasing the availability of the neurotransmitters, and possibly relieving depressive symptoms.

There are two isoforms of monoamine oxidase, MAO-A (generally related to serotonin, melatonin, epinephrine and norepinephrine) and MAO-B (deaminates phenylethylamine and trace amines). Dopamine is equally degraded by both types
and different types of MAOIs act on either or both of these.
Early MAOIs are irreversible in that they permanently deactivate the MAO and the enzyme is not functional for about two weeks, when it has been replaced.
A few newer MAOIs, notably moclobemide, are reversible, meaning that they are able to detach from the enzyme to allow for regular processing.

MAOIs are also selective to the type of the MAO receptor. Some MAOIs inhibit both MAO-A and MAO-B equally, other MAOIs work on one group specifically.
Common MAOIs include Phenelzine (Nardil), Tranylcypromine (Parnate), Isocarboxazid (Marplan), Moclobemide (Aurorix, Manerix, Moclodura), Selegiline (Selegiline, Eldepryl, Emsam), Nialamide, Iproniazid (Marsilid, Iporzid, Ipronid, Rivivol, Propilniazida), Iproclozide, and Toloxatone.

The most common side effect when taking an MAOI is insomnia. Other common adverse reactions include dry mouth, dizziness, feelings of lightheadedness, an excessive drop in blood pressure when standing, constipation, and weakness. Men taking MAOIs may experience sexual side effects with such symptoms as erectile dysfunction, delayed or painful ejaculation, loss of sexual sensation and anorgasmia (inability to reach orgasm). Some women have reported sexual side effects such as decreased libido and vaginal dryness.

Less common side effects reported include rash, nausea, vomiting, stiff neck, flushing, feelings of fear, chest pain, and headaches.

Symptoms of MAOI overdose include severe anxiety, confusion, seizures or convulsions, severe drowsiness or dizziness, cold clammy skin, rapid and irregular pulse, fever, hallucinations, severe headache, coma, tremors/spasms, excessively high or low blood pressure, muscle stiffness, difficulty breathing, extreme sleep difficulties, or abnormal irritability.

Tyramine, a compound found in many foods, beverages and other substances, has an effect on blood pressure. It is regulated by the MAO, so when taking an MAOI, tyramine can reach dangerous levels, resulting in critically high, and possibly fatal, blood pressure. Therefore, careful dietary restrictions need to be implemented while on a course of MAOIs.

Treatment with moclobemide does not have the same dietary restrictions as with other MAOIs, though caution should still be taken with foods high in tyramine.

A new study looked to re-examine the effects of MAOIs in treating bipolar disorder and found that they had positive treatment outcomes.

MAOIs have many negative drug interactions and combinations need to be monitored closely. Combinations of MAOI/TCA (tricylcic antidepressants) are risky, but possible.
Overall, it appears from the literature that the combination of MAOIs and TCAs can be relatively safe and effective in the treatment of patients whose depression is treatment-resistant. On the other hand, the risks associated with MAOI and TCA treatment have made this strategy relatively unpopular since the introduction of the newer agents.”

A 3 year follow up study confirms the safety of MAOI/TCA combos.

“The combination of amitriptyline and trimipramine with MAOIs appears to be safe, but imipramine and clomipramine should definitely be avoided because of the risk of fatal serotonin toxicity. It is usually thought best to start the MAOI and TCA treatment simultaneously at low dose or cautiously to add MAOI treatment to established TCA medication.”


Some old (1988) clinical evidence for MAOI/lithium combos:
“Lithium combined with phenelzine alleviated the symptoms of four severely depressed patients. Previously, all four patients had failed to respond to tricyclic antidepressants, and three had not responded to monoamine oxidase inhibitors.”

Two other studies indicate an MAOI/Li combo is beneficial. Both of these studies had their limitations, but really, what study doesn’t?

The following dietary precautions came from here.

Foods to Avoid

This list consists of foods with sufficient tyramine (in small or usual serving sizes) to create a dangerous elevation in blood pressure and which therefore should be avoided (McCabe, 1986).

• Alcoholic beverages - avoid Chianti wine and vermouth. Consumption of red, white, and port wine in quantities less than 120 mL present little risk (Anon, 1989; Da Prada et al, 1988; McCabe, 1986). Beer and ale should also be avoided (McCabe, 1986), however other investigators feel major domestic (US) brands of beer is safe in small quantities (1/2 cup or less than 120 mL) (Anon, 1989; Da Prada, 1988), but imported beer should not be consumed unless a specific brand is known to be safe. Whiskey and liqueurs such as Drambuie(R) and Chartreuse(R) have caused reactions. Nonalcoholic beverages (alcohol- free beer and wines) may contain tyramine and should be avoided (Anon, 1989; Stockley, 1993).
• Banana peels - a single case report implicates a banana as the causative agent, which involved the consumption of whole stewed green banana, including the peel. Ripe banana pulp contains 7 mcg/gram of tyramine compared to a peel which contains 65 mcg/gram and 700 mcg of tyramine and dopamine, respectively (McCabe, 1986).
• Bean curd - fermented bean curd, fermented soya bean, soya bean pastes contain a significant amount of tyramine (Anon, 1989).
• Broad (fava) bean pods - these beans contain dopa, not tyramine, which is metabolized to dopamine and may cause a pressor reaction and therefore should not be eaten particularly if overripe (McCabe, 1986; Anon, 1989; Brown & Bryant, 1988).
• Cheese - tyramine content cannot be predicted based on appearance, flavor, or variety and therefore should be avoided. Cream cheese and cottage cheese have no detectable level of tyramine (McCabe, 1986; Anon, 1989, Brown & Bryant, 1988).
• Fish - fresh fish (Anon, 1989; McCabe, 1986) and vacuum- packed pickled fish or caviar contain only small amounts of tyramine and are safe if consumed promptly or refrigerated for short periods; longer storage may be dangerous (Anon, 1989). Smoked, fermented, pickled (Herring) and otherwise aged fish, meat, or any spoiled food may contain high levels of tyramine and should be avoided (Anon, 1989; Brown & Bryant, 1988).
• Ginseng - some preparations have resulted in a headache, tremulousness, and manic-like symptoms (Anon, 1989).
• Protein extracts - three brands of meat extract contained 95, 206, and 304 mcg/gram of tyramine and therefore meat extracts should be avoided (McCabe, 1986). Avoid liquid and powdered protein dietary supplements (Anon, 1989).
• Meat, nonfresh or liver - no detectable levels identified in fresh chicken livers; high tyramine content found in spoiled or unfresh livers (McCabe, 1986). Fresh meat is safe, caution suggested in restaurants (Anon, 1989; Da Prada et al, 1988).
• Sausage, bologna, pepperoni and salami contain large amounts of tyramine (Anon, 1989; Da Prada et al, 1988; McCabe, 1986). No detectable tyramine levels were identified in country cured ham (McCabe, 1986).
• Sauerkraut - tyramine content has varied from 20 to 95 mcg/gram and should be avoided (McCabe, 1986).
• Shrimp paste - contain a large amount of tyramine (Anon, 1989).
• Soups - should be avoided as protein extracts may be present; miso soup is prepared from fermented bean curd and contain tyramine in large amounts and should not be consumed (Anon, 1989).
• Yeast, Brewer's or extracts - yeast extracts (Marmite) which are spread on bread or mixed with water, Brewer's yeast, or yeast vitamin supplements should not be consumed. Yeast used in baking is safe (Anon, 1989; Da Prada et al, 1988; McCabe, 1986).

Foods to Use with Caution
This list categorizes foods that have been reported to cause a hypertensive crisis if foods were consumed in large quantities or stored for prolonged periods, or if contamination occurred. Small servings (1/2 cup, or less than 120 mL) of the following foods are not expected to pose a risk for patients on MAOI therapy (McCabe, 1986).
• Alcoholic beverages - see under foods to avoid.
• Avocados - contain tyramine, particularly overripe (Anon, 1989) but may be used in small amounts if not overripened (McCabe, 1986).
• Caffeine - contains a weak pressor agent, large amounts may cause a reaction (Anon, 1989).
• Chocolate - is safe to ingest for most patients, unless consumed in large amounts (Anon, 1989; McCabe, 1986).
• Dairy products - Cream, sour cream, cottage cheese, cream cheese, yogurt, or milk should pose little risk unless prolonged storage or lack of sanitation standards exists (Anon, 1989; McCabe, 1986). Products should not be used if close to the expiration date (McCabe, 1986).
• Nuts - large quantities of peanuts were implicated in a hypertensive reaction and headache. Coconuts and brazil nuts have also been implicated, however no analysis of the tyramine content was performed (McCabe, 1986).
• Raspberries - contain tyramine and small amounts are expected to be safe (McCabe, 1986).
• Soy sauce - has been reported to contain large amounts of tyramine and reactions have been reported with teriyaki (Anon, 1989), however analysis of soy sauce reveals a tyramine level of 1.76 mcg/mL and fermented meat may have contributed to the previously reported reactions (McCabe, 1986).
• Spinach, New Zealand prickly or hot weather - large amounts have resulted in a reaction (Anon, 1989; McCabe, 1986).

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