Monoamine oxidase inhibitors (MAOIs) were the first medications approved for the treatment of depression symptoms and are also used to treat several other medical conditions, such as Parkinson's disease and bulimia nervosa.

History of MAOIs

In 1951, scientists discovered that Iproniazid, a hydrazine derivative of Isoniazid used to treat tuberculosis, seemed to benefit people who were also experiencing depression. Scientists and physicians noted visible positive changes in mood, happiness, and alertness for those taking the drug. In the mid-1950s, Iproniazid was approved as one of the antidepressant drugs. This drug, however, has been discontinued because of the damage it may cause to a person's liver. The discovery of Iproniazid's positive effects in depression treatment have since encouraged researchers to create new formulas and antidepressant drugs for the market.

How Do MAOIs Work?

Monoamine oxidase is an enzyme present in the liver, nerve tissues, gastrointestinal tract, and lungs. It is responsible for the deamination (removal of amine group) of various amines, such as dopamine, serotonin (5-HT), norepinephrine, and epinephrine. All these substances are neurotransmitters that help the brain communicate messages of alertness, happiness, and joy to the body. For a person experiencing depression, these neurotransmitters are usually found in low quantities. Under this circumstance, MAOIs are useful in balancing the level of neurotransmitters and helping a person find relief from symptoms of depression.

When the activity of monoamine oxidase is restricted, the concentration of vital neurotransmitters increases in the central nervous system. Since there is no breakdown of these chemicals, a large quantity remains. Altering this process usually enhances mood and happiness. The monoamine oxidase enzyme is also important in the digestive process, which explains many of the possible severe interactions and side effects that may result from taking this category of drug.

The most commonly prescribed MAOIs are Marplan (isocarboxazid), Nardil (phenelzine), Emsam (selegiline), and Parnate (tranylcypromine). Most MAOIs come in the form of a pill, but recently manufacturers have also developed a skin patch. The skin patch is thought to be more easily tolerated and may cause fewer side effects, especially at lower doses.

Precautions and Contraindications

MAOIs are typically not a doctor or psychiatrist's first choice to treat depression or anxiety. Their use is only advisable when other regimens and therapies (SSRIs or TCAs) are ineffective or prohibited, as they may produce serious adverse effects. They should be used only under the supervision of a trained health clinician. A person who takes these drugs should report any changes to his or her health to a pharmacist, doctor, or other healthcare provider.

Additionally, it should be noted that this category of drug tends to work best when paired with some form of psychotherapy. Antidepressant medications can be helpful in controlling symptoms and assisting a person in achieving meaningful, lasting changes to their mental health, but pills alone do not address behavioral, emotional, or underlying causes for mental health issues. If you are prescribed an antidepressant, please consider finding a qualified therapist to help you work on a plan to understand and cope with your condition. 

Possible Side Effects and Adverse Drug Reactions

Most psychotropic medications come with the potential for unwanted side effects. MAOIs have been associated with side effects that may affect various aspects of a person's health.

  • Cardiovascular Effects: Orthostatic hypotension, the medical term for when you feel dizzy after standing up too quickly, is a common adverse effect. Hypertensive crisis, or extremely high blood pressure, with fever and headache have been registered in people taking Nardil (phenelzine) and Parnate (tranylcypromine).
  • Gastrointestinal Effects: Constipation, dry mouth, anorexia, weight gain, and nausea are commonly reported side effects.
  • Nervous System Effects: Common side effects include dizziness, headache (not related to blood pressure), drowsiness, sleep disturbances (insomnia, hypersomnia), confusion, and memory loss. At high doses, intensifying symptoms of anxiety, depression, and suicidal ideation have been documented.
  • Effects on the Liver: Jaundice and an increase in plasma transaminase concentration are some possibly dangerous side effects. Liver damage is likely when a person is already suffering from chronic liver disease.
  • Effects on the Urinary and Reproductive System: Impotence, delayed and premature ejaculation, and anorgasmia are reported with Nardil (phenelzine) and Parnate (tranylcypromine). Urinary retention, frequency, and inconsistency are also sometimes an issue.
  • Hypertension: A person's history of hypertension must be noted before starting MAOIs. During treatment, blood pressure should be monitored. Dose adjustment is important if a person shows elevated levels of blood pressure. If there is a severe headache with palpitations, the medication should be discontinued.
  • Other Effects: Visual disturbances, thrombocytopenia (low blood platelet count), anemia (low concentration of healthy red blood cells), arthralgia (joint pain), and lupus-like symptoms (drug-induced lupus erythematosus) are reported by some people who take these drugs.

Possible Adverse Drug Interactions

Ingesting certain substances or drugs while taking an MAOI can increase the risk of certain health complications. It is important to note that these medications may negatively interact with the following substances:

  • Food: Avoid foods high in tyramine, tryptophan, and foods that increase dopamine production (foods high in amino acids, tyrosine, and protein). Some examples include:
    • Processed cheese products
    • Aged cheese
    • Wine

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    • Champagne
    • Reduced or alcohol-free wine products
    • Beer (alcoholic and non-alcoholic)
    • Red meat
    • Figs
    • Bananas
  • Other Antidepressants: MAOIs should not be used with other antidepressants unless there is no other possible alternative available, and this decision should always be reached between a person and his or her doctor. MAOIs combined with SSRIs, TCAs, or SNRIs may cause serotonin syndrome, which occurs when two drugs taken at the same time increase serotonin in the brain.
  • Central Nervous System Depressants: The use of these drugs with central nervous system depressants such as opiates, analgesics, barbiturates, sedatives, or hypnotics may induce extra sleep and hypotension.
  • Hypotensive Agents and Diuretics: Using these medications with hypotensive agents and diuretics is associated with a marked decline in blood pressure.

Other Physical and Mental Health Risks

Before starting any antidepressant, be sure to discuss your complete health history with your doctor or psychiatrist. While on this medication you should monitor your health on a regular basis, especially with regards to the following conditions:

  • Hypertension: A person's history of hypertension must be noted before starting MAOIs. During treatment with this class of drugs, blood pressure should be regularly monitored. Dose adjustment may be necessary if a person experiences elevated blood pressure. If there is a severe headache with palpitations, treatment should be discontinued.
  • Bipolar: These drugs may cause mood swings for people experiencing depression or lead to mania. Under these conditions, the dose should be reduced or the use discontinued if recommended by a doctor.
  • Suicidal Risk and Increased Depression: People taking MAOIs may face an intense episode of depression and/or suicidal ideation. The U.S. Food and Drug Administration recommends reducing the dose if this occurs and urges doctors to monitor a person in treatment for changes in mood and behavior.
  • Chest Pain: Some MAOIs may suppress the pain associated with angina. A person using this class of drug should be aware of any exertion that might cause chest pain.
  • Pregnancy: There is not enough data available yet concerning this medication and pregnancy, but in animals MAOIs have produced birth defects. Their use is generally not recommended during pregnancy or for nursing mothers and any risks should be discussed and weighed with a person's doctor before treatment.

Monoamine Oxidase Inhibitor Withdrawal

If you decide to stop taking an MAOI, it is important to taper off one's dosage of the medication rather than stopping it abruptly. A washout period of at least 15 days is required after the discontinuation of MAOI therapy. Severe withdrawal symptoms are possible, including psychosis and convulsions. Contact your doctor if you experience negative withdrawal affects.

Today, monoamine oxidase inhibitors are often seen as a "last resort" treatment when other antidepressants have failed. For various reasons, some individuals do not respond well to newer classes of antidepressants. In these cases, doctors often fall back upon older formulations, such as MAOIs or tricyclics. Researchers believe that genetic profiling may someday offer guidance to doctors when selecting an antidepressant, but such innovations are not available at this time.


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  5. Hirschfeld, R.M. (2000). Antidepressants in Long-term Therapy: A Review of Tricyclic Antidepressants and Selective Serotonin Reuptake Inhibitors. Acta Psychiatr Scand Suppl, 403, 35.
  6. Stein, D.J., Kupfer, D.J., and Schatzberg, A.F. (2006). American Psychiatric Publishing Textbook of Mood Disorders. American Psychiatric Publishing, Inc.

Page content reviewed by James Pendleton, ND