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.
5 examples of MAOI depression medications
Examples of oral MAOIs include:
- rasagiline (Azilect),
- selegiline (Eldepryl, Zelapar),
- isocarboxazid (Marplan),
- phenelzine (Nardil), and
- 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.