How MAOIs Work and Common Side Effects

Monoamine oxidase inhibitors (MAOIs) are a class of drugs developed in the 1950s. They're 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.

If you have been prescribed an MAOI, it's helpful to know how it works. It's also important to know the potential side effects to watch for and how to take this type of drug safely. But first, let's talk about drugs that are categorized as MAOIs.

MAOI Drugs

Some common MAOIs include:

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

These MAOIs are approved by the U.S. Food and Drug Administration (FDA) to treat depression. They may also be prescribed off-label to treat other conditions.

How MAOIs Work

The brain contains numerous different types of neurotransmitters (chemical messengers) 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 mood, sleep, appetite, learning, memory, and sexual behavior.
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.
   

Common Side Effects of MAOIs

This list is not all-inclusive and you may experience other side effects not mentioned here. That said, some of the adverse effects you may experience with MAOIs include:

• Convulsions
• Drowsiness
• Extreme mood changes (hypomania)
• High blood pressure
• Impotence
• Loss of consciousness
  
• Rash
• Swelling or puffiness (edema)
• Tingling or pricking sensations (paresthesias)
• Urinary retention
• 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.

Precautions and Contraindications

Before beginning MAOI therapy, tell your healthcare provider if you have any medical conditions, including:

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

Do not take any medications without your physician’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.

Pregnancy

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 physician.

MAOI 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:

• Agitation
• Movement disorders
• Sleep issues
• Speech problems

Some people experience more severe discontinuation symptoms when stopping MAOIs, such as feelings of aggression, unresponsiveness while awake (catatonia), cognitive impairment, and psychosis. If this occurs for you or a loved one, seek immediate medical attention as more intensive management may be required.

Risk of Suicide

The FDA requires that 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. The association of increased suicidal thoughts with antidepressant treatment, especially among adolescents, has been a center of attention and controversy in recent years.

Researchers have not found a definitive answer about the antidepressant-suicide connection. For most people, antidepressants decrease depression and suicidality and alleviate the helplessness and hopelessness that consumes their daily existence. But, for a small percentage of people taking antidepressants, this may not be the case.

If you're concerned about this issue, be open with your healthcare provider. Also, don’t be afraid to ask questions about any antidepressant or other drug you've been prescribed. The more you know about that medication and how it may affect you, the more informed decision you can make about its use.