Laura Hack, MD, PhD, is an assistant professor of psychiatry and behavioral sciences at Stanford University in California. She explains that MAOIs “work by blocking enzymes that break down important mood-related chemicals in the brain — specifically serotonin, norepinephrine, and dopamine.” This causes higher levels of these monoamines.

For some time, scientists believed that low neurotransmitter levels were the only basis for depression. This is because “people often became depressed when given medications that depleted these chemicals, and when recovering patients had their serotonin levels artificially lowered, their depression frequently returned,” says Dr. Hack.

Scientists now think that depression is much more complicated than this. Hack states that “while MAOIs increase brain chemicals almost immediately, it typically takes several weeks before patients notice improvements in their mood.” This suggests that depression involves more than just low monoamine levels. More research is therefore needed to understand depression and its treatment with MAOIs.

MAOIs are prescription medications. Doctors classify MAOIs into several types.

Enzyme Selectivity

There are two forms of monoamine oxidase, MAO-A and MAO-B. As Hack explains, some MAOIs are nonselective, meaning they affect both. Such MAOIs include:

• phenelzine
• tranylcypromine
• isocarboxazid

Reversibility

Hack notes that some MAOIs form permanent bonds with MAO enzymes, inhibiting them for as long as they exist. These are irreversible MAOIs, which include phenelzine and tranylcypromine. By contrast, reversible inhibitors (RIMAs) like moclobemide bind to MAO enzymes only temporarily. Other medications can undo this bond, meaning that RIMAs are less likely to interact with other drugs.

Administration

• isocarboxazid
• phenelzine
• tranylcypromine

What Are the Possible Side Effects of MAOIs?

Jonathan E. Alpert, MD, PhD, is the chair of the APA’s Council on Research and the Silverman University Chair in the department of psychiatry and behavioral sciences at Montefiore Medical Center and Albert Einstein College of Medicine in Bronx, New York. He says that “monoamines are ubiquitous in the brain and body and have myriad effects on multiple domains of function.” These include:

• Appetite and metabolism
• Blood pressure
• Sexual function
• Sleep

In addition, “MAO enzymes are found in both brain and gut and have important interactions with other medications (including other serotonin acting drugs and medications that affect constriction of blood vessels) as well as certain kinds of food (such as aged or fermented foods).” For these reasons, MAOIs can have many side effects.

Dr. Alpert lists the following:

• Dangerously high blood pressure
• Insomnia
• Dizziness
• Feeling agitated
• Sexual dysfunction
• Weight gain
• Low blood pressure when getting up

Are There Any Risks Related to MAOIs?

When combined with antidepressants or serotonin-altering medications, MAOIs can cause serotonin syndrome. This occurs when there is too much serotonin in a person’s body. Serotonin syndrome can cause the following symptoms:

• Delirium
• Changes in vital signs such as hypertension, tachycardia, and fever
• Diarrhea
• Tremors

If you are taking MAOIs and experience these symptoms, seek immediate medical advice. Without treatment, serotonin syndrome is a life-threatening condition.

The Takeaway

• MAOIs affect certain enzymes inside the brain, causing higher levels of certain neurotransmitters.
• These drugs can improve symptoms of mental health conditions, like depression and panic disorder.
• They come with certain risks and side effects, which can be serious. Speak with your doctor to find out whether MAOIs are the right drug for you.