How MAOIs Work and Common Side Effects

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Monoamine oxidase inhibitors (MAOIs) are a class of drugs that were developed in the 1950s. They're quite effective in treating depression, panic disorder, and other anxiety disorders. They're used less frequently than selective serotonin reuptake inhibitors (SSRIs) and other antidepressants because of necessary dietary precautions and risks of adverse reactions when mixed with certain drugs.

Some common MAOIs include:

  • Emsam (selegiline)
  • Marplan (isocarboxazid)
  • Nardil (phenelzine)
  • Parnate (tranylcypromine)

Emsam is a transdermal (skin) patch that's applied once a day. This mode of administration may be less likely to cause the dietary complications associated with an oral route of administration.

How MAOIs Work

The brain contains numerous different types of chemical messengers (neurotransmitters) that act as communication agents between different brain cells. These chemical messengers are molecular substances that can affect mood, appetite, anxiety, sleep, heart rate, temperature, aggression, fear, and many other psychological and physical functions. Monoamine oxidase (MAO) is an enzyme that degrades or breaks down three neurotransmitters associated with mood and anxiety:

  1. Serotonin: This neurotransmitter plays a role in modulating anxiety, mood, sleep, appetite, and sexuality.
  2. Norepinephrine: Also known as noradrenaline, norepinephrine influences sleep and alertness and is believed to be correlated to the fight-or-flight stress response.
  3. Dopamine: Besides influencing body movement, dopamine is also believed to be involved in motivation, reward, reinforcement, and addictive behaviors. Many theories of psychosis suggest that dopamine plays a role in psychotic symptoms.

MAOIs reduce the activity of the enzyme MAO. Less MAO results in higher levels of norepinephrine, serotonin, and dopamine in the brain. The benefits of these increases are improved mood and anti-anxiety effects.

Common Side Effects of MAOIs

This list is not all-inclusive and you may experience other side effects not mentioned here. You should report all medication-related side effects to your doctor.

  • Confusion
  • Decreased sleep/insomnia
  • Diarrhea
  • Dizziness
  • Dry mouth
  • Edema (water retention)
  • Hypertension (high blood pressure)
  • Hypotension (low blood pressure)
  • Muscle spasms
  • Nausea
  • Sexual dysfunction
  • Weakness
  • Weight gain

Tyramine-Induced Hypertension Crisis

Tyramine is a compound found in many foods. This compound has an effect on blood pressure and is regulated by the MAO enzyme. When the MAO enzyme is inhibited (for instance, when you take an MAOI), tyramine can reach dangerously high levels, resulting in critically high blood pressure.

While taking an MAOI, it will be necessary to avoid foods and beverages high in tyramine to prevent potentially fatal high blood pressure spikes.

Other Precautions and Contraindications

Before beginning MAOI therapy, tell your doctor if you have any medical conditions including the following::

  • Cardiovascular disease (i.e., previous heart attack, heart disease)
  • Diabetes
  • Hyperthyroidism (overactive thyroid)
  • Hypertension (high blood pressure)
  • Renal disease (kidney disease)
  • Seizure disorder

Tell all of your treating providers that you're taking an MAOI. This includes physicians, physician assistants, dentists, and other healthcare providers.

Do not take any medications without your doctor’s approval.

Serotonin Syndrome

Dangerously high levels of serotonin in the brain can cause a potentially life-threatening condition called serotonin syndrome. This rare condition is usually the result of an interaction of two or more drugs that affect brain serotonin levels. Even some over-the-counter supplements, such as St. John’s Wort, can result in serotonin syndrome if mixed with MAOIs.

To reduce the risk of serotonin syndrome, MAOIs should never be taken with SSRIs or TCAs. It's recommended that other antidepressant therapy not begin until 10 to 14 days after discontinuation of an MAOI.


The research on pregnancy and MAOI therapy is limited. It's generally recommended that MAOI therapy is avoided during pregnancy. If you're nursing or pregnant, it's best to discuss the risks and benefits of MAOI therapy with your doctor.

Discontinuation Syndrome

Some people have reported withdrawal-like symptoms when decreasing or stopping MAOI therapy. It's believed that these symptoms are a result of the brain trying to stabilize serotonin and norepinephrine levels after an abrupt change.

Symptoms that may occur during discontinuation of MAOI therapy include:

  • Dizziness
  • Electric shock-like sensations in the neck and head
  • Headache
  • Muscle aches
  • Nausea

While none of these symptoms are believed to be dangerous, they can be quite disconcerting. Don't reduce or discontinue MAOI therapy without consulting your doctor.

Risk of Suicide

The association of increased suicidal thoughts with antidepressant treatment, especially among adolescents, has been a center of attention and controversy in recent years. In response to the concerns suggested in some research, the U.S. Food and Drug Administration issued a statement in 2007. Requiring makers of all antidepressant medications include a warning on their products about a possible increased risk of suicidal thinking and behavior in young people up to age 24, particularly during initial treatment.

So far, researchers have not found a definitive answer about the antidepressant-suicide connection. For the vast majority of people, antidepressants decrease depression and suicidality and alleviate the helplessness and hopelessness that consumes their daily existence. But, for a very small percentage of people taking antidepressants, this may not be the case. If you're concerned about this issue, be open with your doctor, and don’t be afraid to ask questions.

If you are having suicidal thoughts, contact the National Suicide Prevention Lifeline at 988 for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.

For more mental health resources, see our National Helpline Database.

8 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. Cassidy CM, Balsam PD, Weinstein JJ, et al. A Perceptual Inference Mechanism for Hallucinations Linked to Striatal Dopamine. Curr Biol. 2018;28(4):503-514.e4.  doi:10.1016/j.cub.2017.12.059

  3. US Food & Drug Administration. Highlights of prescribing information: Emsam.

  4. US Food & Drug Administration. NARDIL® (Phenelzine Sulfate Tablets, USP).

  5. US Food & Drug Administration. Highlights of prescribing information: Parnate.

  6. Dunner DL. Combining antidepressants. Shanghai Arch Psychiatry. 2014;26(6):363-4. doi:10.11919/j.issn.1002-0829.214177

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Additional Reading

By Sheryl Ankrom, MS, LCPC
Sheryl Ankrom is a clinical professional counselor and nationally certified clinical mental health counselor specializing in anxiety disorders.