An MAO inhibitor is a type of medication that blocks an enzyme called monoamine oxidase, which normally breaks down chemical messengers in your brain like serotonin, norepinephrine, and dopamine. By blocking this enzyme, MAO inhibitors allow those brain chemicals to build up to higher levels, which can relieve depression, reduce anxiety, and help manage symptoms of Parkinson’s disease. They were among the first antidepressants ever developed and remain effective today, though they require more caution than newer options due to significant food and drug interactions.
How MAO Inhibitors Work
Your brain relies on chemical messengers called neurotransmitters to regulate mood, motivation, sleep, and movement. Three of the most important are serotonin (which influences mood and anxiety), norepinephrine (which affects alertness and energy), and dopamine (which drives motivation and motor control). After these chemicals do their job, an enzyme called monoamine oxidase breaks them down so they don’t accumulate indefinitely.
There are two forms of this enzyme. MAO-A primarily breaks down serotonin and norepinephrine, while MAO-B primarily breaks down dopamine. Some MAO inhibitors block both forms (these are called non-selective), which broadly raises levels of all three neurotransmitters. Others selectively target just MAO-B, which primarily boosts dopamine. This distinction matters because it determines what each medication is used for and what precautions come with it.
Conditions They Treat
MAO inhibitors are FDA-approved for several conditions, depending on the specific medication:
- Major depressive disorder: Isocarboxazid (Marplan), tranylcypromine (Parnate), and the selegiline patch (Emsam) are all approved for depression.
- Treatment-resistant depression, panic disorder, and social anxiety: Phenelzine (Nardil) is specifically approved for these, making it a go-to when other antidepressants haven’t worked.
- Parkinson’s disease: Selegiline is also approved as an add-on treatment for Parkinson’s, where its selective MAO-B inhibition helps preserve dopamine in brain areas that control movement. Rasagiline, another selective MAO-B inhibitor, is similarly used in early and late Parkinson’s disease, either on its own or alongside other Parkinson’s medications.
MAO inhibitors are not typically the first medication a doctor prescribes for depression. Newer antidepressants like SSRIs generally come with fewer dietary restrictions and drug interactions. But for people whose depression hasn’t responded to other treatments, or for those with atypical depression (characterized by oversleeping, overeating, and heavy feelings in the limbs), MAO inhibitors can be remarkably effective.
The Tyramine Problem
The most distinctive thing about taking a non-selective MAO inhibitor is the dietary restrictions. Your gut normally uses MAO-A to break down a substance called tyramine, which is found naturally in many aged, fermented, and cured foods. When that enzyme is blocked by medication, tyramine enters your bloodstream unchecked and can trigger a dangerous spike in blood pressure known as a hypertensive crisis.
The threshold is surprisingly low. A person not taking an MAO inhibitor can handle 200 to 800 mg of tyramine before seeing any blood pressure change. Someone on an irreversible MAO inhibitor can have a mild reaction from just 6 to 10 mg, and a severe reaction from 10 to 25 mg. That’s a fraction of what a single serving of aged cheese might contain.
Foods to Avoid
The list of high-tyramine foods is extensive and includes many common items:
- Aged and artisan cheeses: cheddar, Swiss, Parmesan, blue cheeses, feta, brie, Camembert, Gruyere, and Edam
- Cured meats: pepperoni, salami, dry sausages, bologna, bacon, and corned beef
- Smoked or processed fish and meats
- Fermented foods: sauerkraut, kimchi, pickles, tofu, miso, and caviar
- Fermented beverages: kombucha, kefir, and especially tap or home-brewed beer and artisan wine
- Fermented sauces: soy sauce, fish sauce, shrimp sauce, Worcestershire sauce, and teriyaki sauce
- Certain produce: fava beans, snow peas, dried fruits, overripe bananas, and overripe avocados
- Yeast-extract spreads: Marmite, Vegemite, and brewer’s yeast
Caffeinated beverages may also contain tyramine, so your prescriber may suggest limiting those as well. Fresh, unaged versions of most foods are generally fine. The rule of thumb: the more a food has been aged, fermented, or left to ripen, the more tyramine it likely contains.
The Transdermal Patch Exception
One important development is the selegiline skin patch (Emsam), which delivers the medication through the skin and into the bloodstream directly, bypassing the gut. At the lowest dose of 6 mg per 24 hours, the FDA has determined that no dietary modifications are necessary. This is because the patch avoids blocking MAO-A in the gut wall, leaving your body’s natural tyramine-processing ability largely intact. At higher patch doses, dietary restrictions apply again, but the lowest dose offers the antidepressant benefit of an MAO inhibitor without the burden of a restricted diet.
Drug Interactions to Know About
Beyond food, MAO inhibitors interact dangerously with a range of other medications. The most serious risk is serotonin syndrome, a potentially life-threatening condition caused by too much serotonin accumulating in the brain. Symptoms include agitation, rapid heartbeat, high body temperature, muscle rigidity, and in severe cases, seizures.
Medications that should not be combined with MAO inhibitors include most other antidepressants (SSRIs, SNRIs, and tricyclics), certain pain medications (particularly those related to opioids that affect serotonin), some cough and cold medicines containing ingredients that raise norepinephrine, and the herbal supplement St. John’s wort. Even switching from an SSRI to an MAO inhibitor requires a washout period of several weeks to let the first drug clear your system.
This is why people taking MAO inhibitors need to inform every healthcare provider they see, including dentists and pharmacists, about their medication. Interactions can happen with drugs that seem unrelated to mental health.
Common Side Effects
Like all antidepressants, MAO inhibitors come with side effects. The most frequently reported include dizziness when standing up quickly (caused by a drop in blood pressure), trouble sleeping, dry mouth, nausea, and weight gain. Some people experience drowsiness or fatigue instead of insomnia. Sexual side effects, including difficulty with arousal or orgasm, also occur, though some evidence suggests they may be less common with MAO inhibitors than with SSRIs.
The blood pressure drop when standing, called orthostatic hypotension, is one of the more noticeable effects. It can cause lightheadedness or even fainting, especially in the first few weeks. Getting up slowly from a seated or lying position helps. Most side effects tend to settle down over time as your body adjusts.
Why They’re Still Prescribed
Given all the precautions, you might wonder why anyone takes MAO inhibitors at all. The answer is that they work, sometimes when nothing else does. For treatment-resistant depression and atypical depression, MAO inhibitors remain among the most effective options available. Some patients who have tried multiple SSRIs, SNRIs, and other newer antidepressants without relief find significant improvement on an MAO inhibitor. The dietary and drug restrictions are a real burden, but for someone who has been struggling with severe depression for months or years, that trade-off is often worth it.
In Parkinson’s disease, selective MAO-B inhibitors like rasagiline play a different but equally important role. By preserving dopamine in the brain, they can improve motor symptoms and may slow disease progression when started early. Because they selectively target MAO-B rather than MAO-A, the dietary restrictions are minimal or absent at standard doses.