Monoamine oxidase inhibitors are a class of antidepressant drugs that are currently used for the treatment of depressive symptoms in individuals who do not respond to other treatments. Except for the aforementioned usage, the use of other classes of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), is preferred. This preference is due to the adverse effects caused by the interaction of monoamine oxidase inhibitors with other medications as well as commonly consumed foods. Monoamine oxidase inhibitors, when used along with the appropriate precautions, remain a useful therapeutic agent for the treatment of depression and other disorders like Parkinson’s disease.

What is a Monoamine Oxidase Inhibitor?

Monoamine oxidase inhibitors (MAOIs) are a class of antidepressants that have been used for over 60 years. The use of these drugs for the treatment of depression waned after the discovery of other antidepressants, such as selective serotonin reuptake inhibitors in the 1980s. Although MAOIs are effective in the treatment of affective (emotional) disorders like depression and anxiety disorders, the newer class of antidepressants are much safer and have fewer side effects. MAOIs are still used today in cases of treatment-resistant depression and have shown promise in the treatment of neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease.

Monoamine oxidase inhibitors, as the name suggests, inhibit the activity of the enzyme monoamine oxidase. This enzyme occurs in two forms, MAO-A and MAO-B and is present in the brain, gut, liver and blood platelets. MAO is involved in the oxidation and inactivation of monoamine neurotransmitters like serotonin, dopamine and norepinephrine. Monoamine oxidase inhibitors may bind to MAO’s reversibly or irreversibly to cause an increase in the concentration of the aforementioned monoamine neurotransmitters.

MAO-A is present in the brain, liver and the gut. The selective inhibition of MAO-A is linked with the antidepressant properties of MAOIs. This aspect is due to the increase in the concentration of the neurotransmitters serotonin and norepinephrine resulting from the selective inhibition of MAO-A.

MAO-B is present in the brain region called the basal ganglia that is involved in the control of voluntary movements. Movement disorders such as Parkinson’s disease are characterized by the loss of dopamine neurons and an increase in MAO-B activity in the basal ganglia. MAOIs that selectively bind MAO-B are used for their ability to slow the progress of Parkinson’s disease in the early stages. Monoamine oxidases are also involved in the oxidation of monoamines found in food, including tyramine and phenethylamine.

Monoamine Oxidase Inhibitors Examples

The FDA-approved monoamine oxidase inhibitors are all irreversible inhibitors of monoamine oxidase. These include:

  • Isocarboxazid:

    Also sold under the brand name Marplan, is a non-selective MAOI (inhibits both MAO-A and MAO-B) used for the treatment of major depressive disorder and anxiety disorders.

  • Phenelzine:

    Phenelzine (Nardil) is another non-selective MAOI that is used for treatment-resistant depression and symptoms of fear and anxiety.

  • Selegiline:

    Selegiline is a selective MAO-B inhibitor (at low doses) and is used in the treatment of Parkinson’s disease. It is sold under brand names such as Eldepryl and Zelapar. Selegiline is also available in the form of a skin patch for the treatment of depression and is sold under the brand name of Emsam. Selegiline is used at high doses for the treatment of depression and at such doses inhibits the activity of both MAO-A and MAO-B.

  • Tranylcypromine:

    Tranylcypromine is sold under the brand name Parnate and is used in the treatment of severe depression.

Side Effects of Monoamine Oxidase Inhibitors

Monoamine oxidase inhibitors are a family of compounds that share some common side effects due to the shared target of these compounds. Other side effects may vary depending upon the chemical structure of these compounds.

  • Common Side Effects of MAOIs:

    Some of the common side effects of monoamine oxidase inhibitors include:

    • Low blood pressure that may lead to weakness and light-headedness
    • Dry mouth
    • Nausea
    • Diarrhea
    • Vomiting
    • Rapid weight gain
    • Insomnia (mostly if the medication is taken during the evening)
    • Sexual dysfunction

    Other less common side effects include:

    • Muscle tension and twitches
    • MAO-A present in the liver and the gut are involved in the oxidation of monoamines such as tyramine that are present in fermented or aged foods such as cheese and meat. MAOIs block the metabolism of tyramine, resulting in increased levels of tyramine in the system upon intake of certain foods. Tyramine causes the activation of the sympathetic nervous system that results in increased blood pressure (or high blood pressure).
    • MAOIs can interact with over-the-counter nasal decongestants like ephedrine and pseudoephedrine to cause hypertension. A hypertensive crisis caused due to the interaction of MAOIs with food or medications is characterized by migraine-like headaches, nausea, blurred vision, difficulty breathing, chest pain and increased heart rate.
    • In rare cases, the elevated blood pressure caused by high tyramine levels can result in cerebral hemorrhage and death. These symptoms emerge within a few minutes of ingestion of food containing tyramine.
    • Liver toxicity caused by MAOIs like phenelzine and isocarboxazid but not tranylcypromine
    • MAOIs should not be taken with selective serotonin reuptake inhibitors (SSRIs). These drugs can result in an increased release of serotonin in the brain leading to serotonin syndrome. Serotonin syndrome is characterized by hyperthermia (fever), confusion, hallucinations, excessive sweating, seizures, arrhythmias (fluctuating heart rate), rhabdomyolysis (skeletal muscle breakdown) and can lead to death. Some opioid pain relievers, when used in combination with MAOIs, can also result in serotonin syndrome.

Foods to Avoid When Taking Monoamine Oxidase Inhibitors

Monoamine oxidase inhibitors block the breakdown of tyramine by the digestive system and can lead to high levels of tyramine. Tyramine is present in various foods, drinks and other medications. High tyramine levels can result in a hypertensive crisis that can be fatal.

Foods containing high levels of tyramine should be avoided while using MAOIs due to the hypertensive effects. Individuals using monoamine oxidase inhibitors should follow a diet that excludes certain foods.

  • Types of Foods to Avoid:

    • Dried or overripe fruits including raisins, prunes
    • Old or improperly stored food
    • Aged cheese
    • Alcohol (not strictly prohibited but must only be consumed in moderation)
    • Aged meats like pepperoni, sausages and salami
    • Pickled fish
    • Fava or broad bean pods
    • Banana
    • Soybean and soybean products including soy sauce
    • Sauerkraut
    • Yeast extract
    • Mild to no effects: Avocados, chocolate, bouillon, chocolate, fresh cheese and meat

Advantages and Disadvantages of Monoamine Oxidase Inhibitors

As described, monoamine oxidase inhibitors can have numerous side effects as well as have severe and occasionally life-threatening, adverse interactions with many medications and food. Furthermore, treatment with MAOIs is not suitable for individuals with liver or kidney disease, cardiovascular diseases, diabetes, history of alcoholism and headaches.

The major disadvantage of using monoamine oxidase inhibitors is that it requires strict compliance by the patient with regards to diet and the use of other medications to prevent serious adverse effects. Under circumstances of strict compliance or careful supervision of drug and food intake by patients, treatment with monoamine oxidase inhibitors carries a small risk of serious adverse effects. Monoamine oxidase inhibitors are especially useful in the treatment of patients who do not respond to treatment with other antidepressants. Monoamine oxidase inhibitors are also useful in the treatment of patients with major depressive disorder with atypical symptoms.

Besides the treatment of depression, Monoamine oxidase inhibitors have emerged as potential therapeutic agents to help slow down the progress of neurodegenerative disorders like Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease. Monoamine oxidase inhibitors may also be useful in preventing damage to other tissues following a stroke or cardiac arrest.