Monoamine Oxidase Inhibitors (MAOI)

Earn CME/CE in your profession:

Continuing Education Activity

Monoamine oxidase inhibitors (MAOIs) are a separate class from other antidepressants, treating different forms of depression and other nervous system disorders such as panic disorder, social phobia, and depression with atypical features. Even though MAOIs were the first antidepressants introduced, they are not the first choice in treating mental health disorders due to several dietary restrictions, side effects, and safety concerns. MAOIs are only a treatment option when all other medications are unsuccessful. This activity will highlight the mechanism of action, adverse event profile, pharmacology, monitoring, and relevant interactions of MAOIs, pertinent for members of the interprofessional team in treating patients with conditions where this drug class has a therapeutic purpose.


  • Summarize the mechanisms of actions of the MAOI class of drugs.
  • Identify the approved and off-label indications for MAOI therapy.
  • Review the adverse event profile of MAOIs.
  • Outline the importance of collaboration and communication among interprofessional team members to improve outcomes and treatment efficacy for patients who might benefit from MAOI therapy.


Monoamine oxidase inhibitors (MAOIs) were first introduced in the 1950s.[1][2] They are a separate class from other antidepressants, treating different forms of depression as well as other nervous system disorders such as panic disorder, social phobia, and depression with atypical features.[3] Examples of atypical features are oversleeping and overeating. Even though MAOIs were the first antidepressants introduced, they are not the first choice in treating mental health disorders due to several dietary restrictions, side effects, and safety concerns. MAOIs are only a treatment option when all other medications are unsuccessful.

Furthermore, examples of neurological disorders that can benefit from MAOIs are patients with Parkinson disease and those diagnosed with multiple system atrophy.[4][5]  Multiple system atrophy is a neurodegenerative disease that includes symptoms affecting movement as well as blood pressure. 

Mechanism of Action

Monoamine oxidase inhibitors are responsible for blocking the monoamine oxidase enzyme. The monoamine oxidase enzyme breaks down different types of neurotransmitters from the brain: norepinephrine, serotonin, dopamine, and tyramine. MAOIs inhibit the breakdown of these neurotransmitters thus, increasing their levels and allowing them to continue to influence the cells that have been affected by depression.[6]

There are two types of monoamine oxidase, A and B. The MAO A is mostly distributed in the placenta, gut, and liver, but MAO B is present in the brain, liver, and platelets. Serotonin and noradrenaline are substrates of MAO A, but phenylethylamine, methylhistamine, and tryptamine are substrates of MAO B. Dopamine and tyramine are metabolized by both MAO A and B. Selegiline and rasagiline are irreversible and selective inhibitors of MAO type B, but safinamide is a reversible and selective MAO B inhibitor.[7]

MAOIs are reversible or irreversible. Moclobemide is an example of a reversible MAOI I (RIMA), tranylcypromine, phenelzine, isocarboxazid, and selegiline irreversibly inhibit MAO. Selegiline in low doses is a selective, irreversible MAO B inhibitor, but it is no longer selective at higher doses.[8]


MAOI administration is almost always orally but sometimes comes in the form of a skin patch.[1] The skin patches were FDA approved and can be more beneficial to patients than oral dose forms. An example of this is selegiline, which can be given in a skin patch and causes fewer side effects than oral administration.[1] Patients with lower doses of MAOIs may not have to be as strict with their diet as those with higher doses.

The different types of MAOIs approved by the FDA include isocarboxazid, phenelzine, selegiline, and tranylcypromine.[9] When patients are prescribed antidepressants like MAOIs, they must be aware of the time it takes to start experiencing the therapeutic effects of the drug. Usually, the medication starts to become effective within two to three weeks. However, patients should take the antidepressant for at least six months for the maximal therapeutic benefit. Patients who take an antidepressant for less than six months are shown to have a high symptomatic relapse rate.

Adverse Effects

The most frequently encountered side effects are dry mouth, nausea, diarrhea, constipation, drowsiness, insomnia, dizziness, and/or lightheadedness. Furthermore, if applied via patch, a skin reaction may occur at the patch site.[9] Recommendations are that any patient scheduled for an elective surgery that requires general anesthesia should not take MAOIs for at least ten days before the surgery to avoid any drug interaction.[10][11]


MAOIs can potentially cause drug-to-drug interactions, drug-food interaction, and overdoses, of which the patient should be aware.[9] For example, patients should not be mixing MAOIs with other antidepressants like selective serotonin reuptake inhibitors (SSRIs).[12] These two drugs combined can cause serotonin syndrome, which is potentially fatal. The first cases of serotonin syndrome were reported during the 1960s when patients were on MAOIs and tryptophan. Patients showed signs and symptoms of fever, confusion, increased perspiration, muscle rigidity, seizures, liver or kidney problems, fluctuation of heart rhythms, and blood pressure. Furthermore, when changing MAOIs to another antidepressant, patients should give themselves 14 days to pass before initiating the new treatment, to prevent any drug interaction.

MAOIs prevent the breakdown of tyramine found in the body and certain foods, drinks, and other medications. Patients that take MAOIs and consume tyramine-containing foods or drinks will exhibit high serum tyramine level.[13][14] A high level of tyramine can cause a sudden increase in blood pressure, called the tyramine pressor response.[14] Even though it is rare, a high tyramine level can trigger a cerebral hemorrhage, which can even result in death.

Eating foods with high tyramine can trigger a reaction that can have serious consequences.[14] Patients should know that tyramine can increase with the aging of food; they should be encouraged to have fresh foods instead of leftovers or food prepared hours earlier.  Examples of high levels of tyramine in food are types of fish and types of meat, including sausage, turkey, liver, and salami.[15][16] Also, certain fruits can contain tyramine, like overripe fruits, avocados, bananas, raisins, or figs. Further examples are cheeses, alcohol, and fava beans; all of these should be avoided even after two weeks of stopping MAOIs.[16] Anyone taking MAOIs is at risk for an adverse hypertensive reaction, with accompanying morbidity.

Tramadol, meperidine, dextromethorphan, and methadone are contraindicated in patients on MAOIs as they are at high risk for causing serotonin syndrome.[8]

In general, SSRIs, SNRIs, TCAs, bupropion, mirtazapine, St. John's Wort and, sympathomimetic amines, including stimulants, are contraindicated with MAOIs.[8]


Even though MAOIs are no longer a first-line treatment option, they are still in use, and it is essential to note the precautions when initiating treatment.[12] Patients should be encouraged by health providers to carry identification cards or wear a wristband.[9] Patients always need to notify every doctor they encounter, whether dental or medical, to avoid any health consequences, especially due to the medications' influence on the vasculature.


Patients taking MAOIs can overdose and may show similar side effects, as stated above, except with more severe presentation.[17] Anyone on MAOIs may experience symptoms slowly within the first 24 to 48 hours. However, symptoms can be nonspecific, which range from mild to severe to even life-threatening. Depending on the MAOI prescribed, some can cause patients to go into a coma, and others  (e.g., overdosing on tranylcypromine) can result in death.[9] The severity depends on the amount consumed and the type of MAOIs the patient took. For example, phenelzine and tranylcypromine being nonselective and nonreversible, increase the risk of a patient experiencing a hypertensive crisis when ingested with tyramine.  However, selegiline is a selective MAO-B inhibitor with less hypertensive risk.[4] Any patient experiencing any of the following: agitation, flushing, tachycardia, hypotension or hypertension, palpations, twitching, increased deep tendon reflexes, seizures, or high fevers should immediately report to a health provider.[9]

Enhancing Healthcare Team Outcomes

Safety and optimal treatment are vital to patient health. Patients with a history of seizures or epilepsy should avoid MAOIs; these medications can increase the occurrence of seizures. Also, people with a history of alcoholism, angina, severe headaches, blood vessel disease, diabetes, kidney or liver disease, history of a recent heart attack or stroke, overactive thyroid, and pheochromocytoma should not receive MAOI therapy; since this may cause a hypertensive crisis.[2] This caution is also necessary for patients with a family history of depression, any neurological disorders, or even if any family members have attempted suicide. Due to the high risks, patients must provide a complete family history. Educating the patient on the importance of possible risks and side effects of the drug is critical for their well-being. It provides them an opportunity for a better outcome.

Ads with other illnesses, depression, and other psychiatric treatment plans pose multiple dilemmas for physicians.[17] These patients may need to try various medication regimens before achieving effective treatment. Someone experiencing depression or panic attacks may have significant life changes, and usually, the family physician is aware of these changes. While a psychiatric physician is almost always involved with patients dealing with different types of mental health issues, it is important to consult with an interprofessional group specialist that includes a family physician, internal medicine, specialty-trained mental health nurse, neurologist, and pharmacist.[18] Also, all other health providers involved in the patient's care are vital members of the interprofessional team, for example, other nurses and social workers. Each member provides an essential element to the patient's treatment plan. Evidence has shown that promoting interprofessional communication by consulting specialists can improve the outcome of a patient's health and their adherence to the plan.[19] [Level 5]



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