Monoamine Oxidase Inhibitor - Dangers

Dangers

When ingested orally, MAOIs inhibit the catabolism of dietary amines. When foods containing tyramine are consumed (so-called "cheese effect"), the individual may suffer from hypertensive crisis. If foods containing tryptophan are consumed, hyperserotonemia may result. The amount required to cause a reaction varies greatly from individual to individual, and depends on the degree of inhibition, which in turn depends on dosage and selectivity.

The exact mechanism by which tyramine causes a hypertensive reaction is not well-understood, but it is assumed that tyramine displaces norepinephrine from the storage vesicles. This may trigger a cascade in which excessive amounts of norepinephrine can lead to a hypertensive crisis. Another theory suggests that proliferation and accumulation of catecholamines causes hypertensive crisis

Tyrosine, not tyramine, is the precursor to catecholamines. Tyramine is a breakdown product of tyrosine. In the gut and during fermentation, tyrosine, an amino acid, is decarboxylated to tyramine. Under ordinary circumstances, tyramine is deaminated in the liver to an inactive metabolite, but, when the hepatic MAO (primarily MAO-A) is inhibited, the "first-pass" clearance of tyramine is blocked and circulating tyramine levels can climb. Elevated tyramine competes with tyrosine for transport across the blood–brain barrier (via aromatic amino acid transport) where it can then enter adrenergic nerve terminals. Once in the cytoplasmic space, tyramine will be transported via the vesicular monoamine transporter (VMAT) into synaptic vesicles, thereby displacing norepinephrine. The mass transfer of norepinephrine from its vesicular storage space into the extracellular space via mass action can precipitate the hypertensive crisis. Hypertensive crises can sometimes result in stroke or cardiac arrhythmia if not treated. In general, this risk is not present with RIMAs. Both kinds of intestinal MAO inhibition can cause hyperpyrexia, nausea, and psychosis if foods high in levodopa are consumed.

Examples of foods and drinks with potentially high levels of tyramine include liver and fermented substances, such as alcoholic beverages and aged cheeses. (See a List of foods containing tyramine). Examples of levodopa-containing foods include broad beans. These diet restrictions are not necessary for those taking selective MAO-B inhibitors, unless these are being taken in high dosages, as mentioned above.

It deserves separate mention that some meat extracts and yeast extracts (Bovril, Marmite, Vegemite) contain extremely high levels of tyramine, and should not be used with these medications.

When MAOIs were first introduced, these risks were not known, and, over the following four decades, fewer than 100 people have died from hypertensive crisis. Presumed due to the sudden onset and violent appearance of the reaction, MAOIs gained a reputation for being so dangerous that, for a while, they were taken off the market in America entirely. However, it is now believed that, used as directed under the care of a qualified psychiatrist, this class of drugs is a viable alternative treatment for intermediate- to long-term use.

The most significant risk associated with the use of MAOIs is the potential for interactions with over-the-counter and prescription medicines, illicit drugs or medications, and some supplements (e.g., St. John's Wort). It is vital that a doctor supervise such combinations to avoid adverse reactions. For this reason, many users carry an MAOI-card, which lets emergency medical personnel know what drugs to avoid. (E.g., adrenaline dosage should be reduced by 75%, and duration is extended.) The risk of the interaction of MAOI medications with other drugs or certain foods is particularly dangerous because those on the medication who would have to restrict their diets often are depressed patients who "don't care if they live or die."

MAOIs should not be combined with other psychoactive substances (antidepressants, painkillers, stimulants, both legal and illegal etc.) except under expert care. Certain combinations can cause lethal reactions, common examples including SSRIs, tricyclics, MDMA, meperidine, tramadol, and dextromethorphan. Agents with actions on epinephrine, norepinephrine, or dopamine must be administered at much lower doses due to potentiation and prolonged effect.

Nicotine, a substance frequently implicated in tobacco addiction, has been shown to have "relatively weak" addictive properties when administered alone. The addictive potential increases dramatically after co-administration of an MAOI, which specifically causes sensitization of the locomotor response in rats, a measure of addictive potential. This may be reflected in the difficulty of smoking cessation, as tobacco contains naturally-occurring MAOI compounds in addition to the nicotine.