Four MAO inhibitors (MAOIs) are currently approved in the United States: isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), and selegiline (Emsam). The first three are oral tablets used for depression. Selegiline is delivered through a skin patch, which changes some of its safety requirements in a meaningful way.
The Four Approved MAOIs
Isocarboxazid, phenelzine, and tranylcypromine are all taken by mouth and work broadly on the same enzyme system. They’re classified as non-selective, meaning they block both major forms of the monoamine oxidase enzyme (MAO-A and MAO-B). This makes them effective for depression but also means they come with strict dietary rules.
Selegiline stands apart. It’s applied as a daily patch, which allows the drug to enter the bloodstream without passing through the gut. At its lowest dose (6 mg/24 hours), the FDA does not require dietary restrictions, a significant advantage over the oral MAOIs. At higher doses (9 mg or 12 mg/24 hours), the same food restrictions apply as with the oral versions.
How MAOIs Work
Your brain uses chemical messengers called neurotransmitters, including serotonin, norepinephrine, and dopamine, to regulate mood. Normally, an enzyme called monoamine oxidase breaks these chemicals down after they’ve done their job. MAOIs block that enzyme, so more of these neurotransmitters remain active in the brain. The result is a lift in mood that can be powerful, especially in people who haven’t responded to other antidepressants.
Who Takes Them
MAOIs are currently considered third-line medications for treatment-resistant depression, which means they’re typically tried after other antidepressants (like SSRIs or SNRIs) haven’t worked. They are markedly underutilized. A 2025 review in Pharmacological Research described MAOIs as “potentially lifesaving for severely affected individuals” and argued that clinicians need to revisit these drugs rather than overlook them. For people who have failed multiple treatments, an MAOI can be a turning point.
The Tyramine Problem
The biggest practical issue with MAOIs is their interaction with a substance called tyramine, found naturally in many foods. Your body normally uses the same monoamine oxidase enzyme to break down tyramine in the gut. When that enzyme is blocked by an MAOI, tyramine can build up rapidly and cause a dangerous spike in blood pressure. This reaction was historically called the “cheese effect” because aged cheese was a common trigger.
The list of foods to avoid is longer than most people expect:
- Aged and artisan cheeses: cheddar, Swiss, Parmesan, blue cheeses like Stilton and Gorgonzola, brie, Camembert, feta, Gruyere, and Edam
- Cured and processed meats: pepperoni, salami, dry sausages, bologna, bacon, corned beef, and smoked or cured fish
- Fermented and pickled foods: sauerkraut, kimchi, pickles, pickled fish, caviar, and tofu
- Certain produce: fava beans and their pods, snow peas, dried or overripe fruits (raisins, overripe bananas, overripe avocados)
- Yeast-extract spreads: Marmite, Vegemite, and brewer’s yeast
- Alcohol: especially tap or home-brewed beer and artisan wine
- Other: meat tenderizers, artisan sourdough bread, improperly stored or spoiled foods, and caffeinated beverages (which may also contain tyramine)
This dietary vigilance is required for the entire time you take an oral MAOI and, as noted above, for selegiline patches at doses above 6 mg. If you reduce from a higher selegiline dose to 6 mg or stop the higher dose entirely, you still need to follow the restrictions for an additional two weeks while the drug clears your system.
Drug Interactions and Switching
MAOIs interact dangerously with a wide range of other medications. The most serious risk is serotonin syndrome, a potentially life-threatening condition caused by too much serotonin activity in the brain. This can happen if an MAOI is combined with SSRIs, SNRIs, certain tricyclic antidepressants, or even some over-the-counter cold and cough medicines that contain ingredients like dextromethorphan.
Because of this risk, switching between an MAOI and another antidepressant requires a washout period. The standard gap is 14 days after stopping an MAOI before starting an SSRI, SNRI, or most other antidepressants. The same 14-day window applies when switching from one MAOI to another. Cross-tapering (gradually lowering one drug while raising another) is not recommended because the overlap period is too risky. If you’re switching to tranylcypromine specifically, your prescriber may start it at half the usual dose for the first week as an extra precaution.
Common Side Effects
Beyond the dietary and drug interaction concerns, MAOIs carry side effects similar to other antidepressants but with a few distinctive patterns. Dizziness when standing up (caused by a drop in blood pressure) is one of the most common. Weight gain, trouble sleeping, daytime drowsiness, dry mouth, and sexual side effects are also frequently reported. Many of these side effects are manageable and may lessen over time, but the blood pressure drops can be persistent enough to require dosage adjustments.
The combination of dietary rules, drug interactions, and side effects explains why MAOIs are reserved for cases where other options have failed. But for the right patient, they remain among the most effective antidepressants available.