MAOIs – Types, Side Effects, and More


Also called: MAO Inhibitors, Monoamine Oxidase Inhibitors, MAOI Drugs


Monoamine oxidase inhibitors (MAOIs) were the first class of antidepressant to be introduced. Today, these drugs are still used, but much less frequently than in the past due to their potential to cause a dangerous spike in blood pressure (hypertensive crisis) when taken with certain types of foods, beverages and medications. Therefore, they are usually prescribed only if newer, safer antidepressants, such as selective serotonin reuptake inhibitors,  fail to relieve a patient’s symptoms.

MAOIs work by blocking monoamine oxidase, an enzyme (protein that catalyzes specific biochemical reactions) in the cells of most tissues that metabolizes neurotransmitters such as dopamine, norepinephrine and serotonin. By blocking this action, the neurotransmitters remain at high levels in the brain, which is believed to boost a person’s mood.

In addition to treating depression, MAOIs may also be prescribed for patients with conditions such as agoraphobia and social anxiety disorder.

Most MAOIs are available in tablet form. However, the U.S. Food and Drug Administration (FDA) recently approved an MAOI in the form of a skin patch (applied daily) for the treatment of depression.   

Individuals who take MAOIs must adhere closely to a medication and diet regimen that will reduce the risk of drug interactions and an adverse hypertensive reaction.

MAOIs are not typically prescribed for children or adults over the age of 60. Women who are pregnant or thinking about becoming pregnant should consult their physician before taking these drugs as studies have indicated that MAOIs may cause birth defects.

About MAOIs

Monoamine oxidase inhibitors (MAOIs) were introduced in the 1950s as the first antidepressant. Today, these drugs are not usually the first choice in treating mental health disorders because they sometimes cause an adverse hypertensive (high blood pressure) reaction. Instead, they are used primarily when other medications have failed to relieve symptoms associated with depression or panic disorder.

MAOIs work by blocking monoamine oxidase, an enzyme (protein that catalyzes specific biochemical reactions) in the cells of most tissues that metabolizes neurotransmitters such as dopamine, norepinephrine and serotonin. By blocking this action, the neurotransmitters remain at high levels in the brain, which is thought to boost a person’s mood.

Most MAOIs are available in tablet form. However, the U.S. Food and Drug Administration (FDA) recently approved an MAOI in the form of a skin patch (applied daily) for the treatment of depression. 

Certain foods, beverages or medications that contain the amino acid tyramine may interact poorly with MAOI tablets or a high-dose MAOI patch. As a result, patients who take MAOI MAOI tablets or use high-dose patches must closely adhere to a medication and diet regimen that will reduce the risk of this type of reaction.

It takes time for the enzyme-blocking action of MAOIs to improve patient symptoms. Patients who take antidepressants such as MAOIs will usually begin to feel beneficial effects within two to three weeks. In general, patients should continue to take antidepressants for at least six months – those who quit before that time have a high rate of symptom relapse.

The FDA has approved four types of MAOIs for treating depression and anxiety disorders. They are:

Generic NameBrand Name

Conditions treated with MAOIs

Because of their potential side effects, monoamine oxidase inhibitors (MAOIs) are not used as a first-choice treatment for any mental health disorders. Nonetheless, these drugs may be effective in patients who find that other forms of antidepressants do not alleviate symptoms.

Conditions known to be effectively treated with MAOIs include panic disorder, social phobia and depression with atypical features (characterized by oversleeping and overeating).

Conditions of concern with MAOIs

Patients may not be good candidates for monoamine oxidase inhibitors (MAOIs) treatment if they have been diagnosed with any of the following conditions:

  • Alcoholism

  • Angina (chest pain)

  • Severe or frequent headaches

  • Diabetes

  • Epilepsy (disorder marked by recurring motor, sensory or psychic malfunction)

  • Heart or blood vessel disease

  • Kidney or liver disease

  • Parkinson’s disease (progressive brain disease that causes slowness in movements and hand tremors)

  • History of recent heart attack or stroke

  • Overactive thyroid

  • Pheochromocytoma (tumor of the adrenal gland that may cause hypertension)

It is very important for patients to provide a complete family medical history that includes whether other family members have ever had depression or other psychiatric disorders, or if the patient or any members of the patient’s family have ever attempted suicide.

Although smoking tobacco is not contraindicated, it may reduce the effectiveness of this medication. Therefore, patients should inform their physician if they smoke or use other tobacco products.

Potential side effects of MAOIs

Monoamine oxidase inhibitors (MAOIs) can cause adverse hypertensive (high blood pressure) reactions that may have serious health consequences.

The amino acid tyramine is found in the body and helps to regulate blood pressure. However, certain foods, beverages and medications also contain tyramine. Use of MAOIs prevents tyramine from being broken down in the body. If patients taking MAOIs also consume foods and/or beverages containing tyramine, the tyramine will be absorbed into the body, reaching high levels in the blood. This can cause a sudden increase in blood pressure (hypertensive reaction) that could trigger a stroke (cerebral hemorrhage). This is rare, but in extreme cases it could cause the patient’s death.

Eating foods high in the amino acid tyramine – especially aged and fermented foods – can trigger this reaction. Since the tyramine content in foods may increase as they age, foods should be eaten when they are freshest, and leftovers and foods prepared hours earlier should be avoided. Foods that are high in tyramine and should not be consumed during MAOI therapy (and for two weeks afterward) include:

Food TypeExamples
FishLumpfish roe
Pickled and dried herring
Smoked salmon
Salmon mousse
Meat and sausageSalami
Air-dried sausage
Aged sausage
Smoked meat
Corned beef
Kielbasa sausage
FruitOverripe fruit of any kind
OtherMarmite concentrated yeast extract
Beef bouillon
Soy sauce
Yogurt, sour cream
Pickled foods
Fava beans
Beer including alcohol-free varieties
Wine including alcohol-free varieties

Certain foods and beverages may be safe for people taking MAOIs when eaten in moderation (e.g., fresh bread, caffeine, avocados, bananas). However, a physician should be consulted before consuming any of the foods that contain tyramine.

Patients should seek immediate medical care if they experience a severe, pounding headache in the lower back of the skull, which may indicate a hypertensive reaction. Other symptoms associated with this type of hypertensive reaction include sweating, palpitations and increased blood pressure (which can be detected with a home blood pressure kit). 

A newer MAOI that is currently being studied called moclobemide may have a lower risk of triggering hypertensive reactions. Further, a transdermal (skin patch) formulation called selegiline that considerably reduces the risk of tyramine reaction and lessens the dietary restrictions of MAOI treatment, has recently been approved by the U.S. Food and Drug Administration (FDA).

Patients using the lowest available doses of the selegiline patch (6 milligrams per 24 hours) do not have to restrict their diets as they would if they were taking MAOIs in tablet form or receiving higher doses of the drug.

Patients should be aware that a physician might need to adjust the dosage or change medications to achieve the best results with minimal side effects. In addition, the FDA has advised that antidepressants may increase the risk of suicidal thinking in some patients and all people being treated with them should be monitored closely for unusual changes in behavior. For more information, see antidepressants.

Other common side effects that may occur with MAOI use include sedation, insomnia, agitation, confusion, orthostatic hypotension (low blood pressure that occurs when moving from sitting or lying to standing), edema (excess accumulation of fluid), constipation, nausea, fatigue, dry mouth, decreased urine output, decreased sexual function, muscle twitching, increased appetite and weight gain, blurred vision, trembling and increased perspiration. Patients using the selegiline transdermal patch may experience slight redness or a mild rash at the site where the skin patch was applied.

Drug or other interactions with MAOIs

Patients should consult their physicians before taking any additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications.

Use of sympathomimetic drugs (stimulate part of the autonomic nervous system) such as decongestants can cause a hypertensive reaction. Patients should avoid any cold, sinus and allergy medications containing the ingredients pseudoephedrine, phenylephrine or phenylpropanolamine. They should also avoid the following during MAOI therapy and for two weeks afterward:

  • Amphetamines
  • Antidiabetic agents
  • Antihypertensive medications
  • Buspirone (anti-anxiety drug)
  • Diet medications
  • Disulfiram (alcohol addiction drug)
  • Isoproterenol (bronchodilator)
  • Levodopa (Parkinson’s disease drug)
  • Local anesthetic drugs containing ephedrine or cocaine
  • Meperidine (analgesic sometimes used with anesthesia)
  • Methylphenidate (central nervous system stimulant)
  • Carbamazepine (anti-seizure drug)
  • Herbal medications (e.g., St. John’s wort)

MAOIs should not be taken with other antidepressants, especially selective serotonin reuptake inhibitors (SSRIs). Combining MAOIs with other antidepressants can lead to serotonin syndrome, a potentially fatal condition marked by fever, confusion, fluctuations in heart rhythms and blood pressure, increased perspiration, muscle rigidity, seizures, and problems with the liver or kidneys.

Patients who switch from using MAOIs to using another antidepressant are usually required to allow at least 14 days to elapse before beginning therapy with the new drug. Similar caution must be exercised when switching from another antidepressant to MAOI therapy.

Patients taking MAOIs should avoid elective surgery requiring general anesthesia. MAOIs should be discontinued at least 10 days prior to elective surgery.

Patients using the selegiline transdermal patch should not use oral selegiline or other MAOIs.

Lifestyle considerations with MAOIs

Because of the risk of experiencing serious hypertensive side effects, patients taking monoamine oxidase inhibitors (MAOIs) are generally advised to carry identification cards or to wear identification bracelets that indicate that they are taking these medications. Patients also should inform a physician that they are taking MAOIs before receiving any medications or anesthetics. Patients undergoing dental procedures should also inform their dentist of MAOI use.

Symptoms of MAOI overdose

Symptoms of monoamine oxidase inhibitor (MAOI) overdose  can be similar to the medication’s side effects, but are usually more severe. They may start slowly over a period of 24 to 48 hours and can persist for two weeks. In some cases, they may progress to patient coma and – at least in the case of the MAOI tranylcypromine – death. Patients exhibiting any of these symptoms should contact their physician immediately:

  • Agitation
  • Flushing
  • Tachycardia (rapid heart rate)
  • Hypotension (low blood pressure) or hypertension (high blood pressure)
  • Palpitations
  • Increased motor activity
  • Twitching
  • Increased deep tendon reflexes
  • Seizures
  • Hyperpyrexia (abnormally high fever)
  • Cardiorespiratory arrest

Pregnancy use issues with MAOIs

Women who are pregnant or thinking of becoming pregnant and women who are breastfeeding should consult with a physician before using monoamine oxidase inhibitors (MAOIs).

Some studies have indicated that MAOIs may cause an increased rate of birth defects when taken during the first three months of pregnancy. In animal studies, these drugs caused a slowing of growth and an increase in excitability in newborns when administered in large doses.

Tranylcypromine passes into breast milk, but it is unknown whether or not phenelzine or isocarboxazid also pass into breast milk.

Child use issues with MAOIs

Monoamine oxidase inhibitors (MAOIs) are not recommended to be taken by children under the age of 16 since there are no controlled studies of safety in this age group. Certain antidepressants, notably selective serotonin reuptake inhibitors (SSRIs), are usually the medications prescribed to treat depression in children. In recent years, there has been speculation that antidepressants use may increase the risk of suicidal thinking in children. As a result, the U.S. Food and Drug Administration(FDA) recommends that all children using antidepressants should be closely monitored for unusual behavior.

Elderly use issues with MAOIs

Monoamine oxidase inhibitors (MAOIs) generally should not be taken by adults over the age of 60. Older patients who take MAOIs are especially likely to experience dizziness or lightheadedness.

Questions for your doctor regarding MAOIs

Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following MAOI-related questions:

  1. How do MAOIs differ from other antidepressants?
  2. I’ve heard the MAOIs have significant health risks. What do these risks include?
  3. Why are MAOIs the most appropriate treatment for me?
  4. Which MAOI are you prescribing for me?
  5. Are there any foods or beverages that I should avoid while taking MAOIs?
  6. Are there any over-the-counter drugs that I should avoid while taking MAOIs?
  7. Are there any prescription medications that I should avoid while taking MAOIs?
  8. Which medical conditions may preclude using MAOIs?
  9. Are MAOIs appropriate for pregnant women?
  10. Which side effects, if any, should I report immediately to you?
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