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MAOIs (Monoamine Oxidase Inhibitors) Side Effects

  • What are monoamine oxidase inhibitors (MAOIs)? How do they work (mechanism of action)?
  • What are the side effects of MAOIs?
  • What drugs interact with
    MAOIs?
  • 5 examples of MAOI depression medications
  • Are MAOIs safe to take if I’m pregnant or breastfeeding?
  • Pharmacy Author:

    Omudhome Ogbru, PharmD

    Omudhome Ogbru, PharmD

    Omudhome Ogbru, PharmD

    Dr. Ogbru received his Doctorate in Pharmacy from the University of the Pacific School of Pharmacy in 1995. He completed a Pharmacy Practice Residency at the University of Arizona/University Medical Center in 1996. He was a Professor of Pharmacy Practice and a Regional Clerkship Coordinator for the University of the Pacific School of Pharmacy from 1996-99.

  • Medical and Pharmacy Editor:

    Charles Patrick Davis, MD, PhD

    Charles Patrick Davis, MD, PhD

    Charles Patrick Davis, MD, PhD

    Dr. Charles “Pat” Davis, MD, PhD, is a board certified Emergency Medicine doctor who currently practices as a consultant and staff member for hospitals. He has a PhD in Microbiology (UT at Austin), and the MD (Univ. Texas Medical Branch, Galveston). He is a Clinical Professor (retired) in the Division of Emergency Medicine, UT Health Science Center at San Antonio, and has been the Chief of Emergency Medicine at UT Medical Branch and at UTHSCSA with over 250 publications.

  • Understanding Depression Slideshow
  • Take the Depression Quiz
  • Depression Tips Slideshow
  • What are monoamine oxidase inhibitors (MAOIs)? How do they work (mechanism of action)?
  • What are the side effects of MAOIs?
  • What drugs interact with
    MAOIs?
  • 5 examples of MAOI depression medications
  • Are MAOIs safe to take if I’m pregnant or breastfeeding?

What are monoamine oxidase inhibitors (MAOIs)? How do they work (mechanism of action)?

MAOIs were the first class of antidepressants to be developed. They fell out of favor because of concerns about interactions with certain foods and numerous drug interactions . MAOIs elevate the levels of norepinephrine, serotonin, and dopamine by inhibiting an enzyme called monoamine oxidase. Monoamine oxidase breaks down norepinephrine, serotonin, and dopamine. When monoamine oxidase is inhibited, norepinephrine, serotonin, and dopamine are not broken down, increasing the concentration of all three neurotransmitters in the brain.

MAOIs also are used for the treatment of Parkinson’s disease.

What are the side effects of MAOIs?

Since MAOIs work in the brain and affect neurotransmitters, they have many side effects. Side effects of MAOIs are:

  • Sudden drop in blood pressure upon standing up ( orthostatic hypotension )
  • Lack of strength
  • Weakness
  • Nausea
  • Vomiting
  • Dizziness
  • Drowsiness
  • Headache
  • Fatigue
  • Agitation
  • Abnormal voluntary movement
  • Dry mouth
  • Abdominal pain
  • Anxiety
  • Change in mood or behavior
  • Weight gain
  • Impotence ( erectile dysfunction , ED )

MAOIs also carry boxed warnings of suicidal thinking and suicidal behavior in children, adolescents, and young adults.

What drugs interact with
MAOIs?

MAO inhibitors should be avoided with other antidepressants such as paroxetine fluoxetine , amitriptyline , nortriptyline , bupropion ; pain medications like methadone , tramadol , and meperidine ; dextromethorphan, St. Johns Wort, cyclobenzaprine , and mirtazapine . Such combinations lead to high serotonin levels which may lead to confusion , high blood pressure , tremor , hyperactivity , coma , and death. These medications should not be used within 14 days of stopping an MAOI.

MAOIs also interact with seizure medications like carbamazepine ( Tegretol Tegretol XR, Equetro , Carbatrol )and oxcarbazepine ( Trileptal ) through unknown mechanisms, increasing side effects.

MAOIs are not recommended for use with medications like pseudoephedrine, phenylephrine, ephedrine , and phenylpropanolamine. The combination of MAO inhibitors and these drugs can cause an acute hypertensive episode.

Monoamine oxidase also breaks down tyramine, a chemical present in aged cheese, wines, and other aged foods. Since MAOIs inhibit monoamine oxidase, they decrease the breakdown of tyramine from ingested food, thus increasing the level of tyramine in the body. Excessive tyramine can elevate blood pressure and cause a hypertensive crisis. Patients treated with MAOIs should adhere to recommended dietary modifications that reduce the intake of tyramine.

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5 examples of MAOI depression medications

Examples of oral MAOIs include:

  1. rasagiline ( Azilect ),
  2. selegiline ( Eldepryl , Zelapar),
  3. isocarboxazid (Marplan),
  4. phenelzine (Nardil), and
  5. tranylcypromine (Parnate).

Selegiline is also available in a topical patch form called Emsam.

Are MAOIs safe to take if I’m pregnant or breastfeeding?

  • The FDA classifies MAO inhibitors in pregnancy category C, which means that there is no established evidence of safe and effective use of MAO inhibitor in pregnant women. Therefore, infant risk cannot be ruled out.
  • It is not known whether MAO inhibitors enter breast milk ; however, MAO inhibitors should be avoided in nursing mothers to avoid harm to the fetus.

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Summary

Monoamine oxidase inhibitors (MAOIs, MAOI) is a class of antidepressants. They are infrequently prescribed because of concerns about interactions with particular foods and several drug interactions. Side effects, drug interactions, storage, dosage, and pregnancy safety information should be reviewed prior to taking any medication.

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Medically Reviewed on 9/14/2018
References
REFERENCE: Garcia, E, MD. et al. Monoamine Oxidase Inhibitor Toxicity. Medscape. Updated: Jul 21, 2017.
<https://emedicine.medscape.com/article/815695-overview>



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How MAOIs Work and Common Side Effects



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Panic Disorder



Treatment

How MAOIs Work and Common Side Effects

These drugs are often used to treat depression and anxiety disorders


By Sheryl Ankrom
Updated November 25, 2018



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

    Examples of MAOIs

    • Phenelzine (nardil)
    • Tranylcypromine (parnate)
    • Isocarboxazid ( marplan)
    • Selegiline (emsam)

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

    How MAOIs Work

    It’s believed that the brain contains several hundred 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 occurrences. 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 an anti-panic effect.

    Common Side Effects

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

    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.

    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 (i.e., when taking 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 of the following conditions:

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

    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 is recommended that other antidepressant therapy not begin until 10 to 14 days after discontinuation of an MAOI.

    Pregnancy

    The research on pregnancy and MAOI therapy is limited. It is recommended that MAOI therapy is avoided during pregnancy. If you are nursing or are pregnant, it is 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 is 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:

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

    While all of these symptoms are not believed to be dangerous, they can be quite disconcerting. Do not reduce or discontinue MAOI therapy without consulting your doctor.

    Risk of Suicide

    The association of increased suicidal thoughts , especially among adolescents, with antidepressant treatment, has been a center of attention and controversy in recent years. In response to the concerns suggested in case studies and some research, the U.S. Food and Drug Administration (FDA) issued a statement in 2007. The FDA proposed that makers of all antidepressant medications indicate a warning on their products about a possible increased risk of suicidal thinking and behavior in young adults, ages 18 to 24, 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 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.

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    Article Sources





    • Antidepressant Use in Children, Adolescents, and Adults. Revisions to Product Labeling. U.S. Food and Drug Administration. May 2, 2007.
    • Kaplan MD, Harold I. and Sadock MD, Benjamin J. Synopsis of Psychiatry, Eighth Edition 1998 Baltimore: Williams & Wilkins.



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