MAO inhibitors (MAOIs) are a class of medications that block an enzyme called monoamine oxidase, which normally breaks down mood-regulating brain chemicals like serotonin, dopamine, and norepinephrine. By blocking this enzyme, MAOIs allow those chemicals to build up, lifting mood or improving movement control. There are two main groups: those prescribed for depression and those used for Parkinson’s disease.
MAOIs Approved for Depression
The FDA has approved four MAOIs for treating depression. Three are taken as pills:
- Phenelzine (brand name Nardil)
- Tranylcypromine (brand name Parnate)
- Isocarboxazid (brand name Marplan)
The fourth, selegiline, is delivered through a skin patch sold as Emsam. The patch works differently from the oral versions because it delivers the drug directly into the bloodstream, bypassing the gut. At its lowest dose of 6 mg per 24 hours, the patch doesn’t require the strict diet that oral MAOIs do (more on that below). Higher patch doses of 9 or 12 mg per 24 hours do require dietary restrictions.
These medications are not first-line antidepressants. They’re typically reserved for people who haven’t responded to newer options like SSRIs or SNRIs. That said, some people with treatment-resistant depression find MAOIs uniquely effective where other drugs have failed.
MAOIs Used for Parkinson’s Disease
A related group of MAOIs targets a specific form of the enzyme called MAO-B, which primarily breaks down dopamine. Since Parkinson’s disease involves a loss of dopamine-producing brain cells, blocking MAO-B helps preserve the dopamine that remains. These drugs are often used alongside other Parkinson’s medications.
Three MAO-B inhibitors are commonly prescribed for Parkinson’s:
- Selegiline (Eldepryl), taken as a 5 mg tablet twice daily. An orally dissolving version called Zelapar is also available.
- Rasagiline (Azilect), taken once daily at 0.5 or 1 mg
- Safinamide (Xadago), taken once daily at 50 or 100 mg
Note that selegiline appears in both categories. The oral tablet form at Parkinson’s doses targets MAO-B selectively, while the Emsam patch at higher doses affects both MAO-A and MAO-B, giving it antidepressant effects.
How MAO-A and MAO-B Differ
Your body has two types of the monoamine oxidase enzyme. MAO-A primarily breaks down serotonin and norepinephrine, the chemicals most tied to mood. MAO-B primarily breaks down dopamine, the chemical most tied to movement and motivation. The older antidepressant MAOIs (phenelzine, tranylcypromine, isocarboxazid) block both types, which is why they’re called “non-selective.” The Parkinson’s drugs are selective for MAO-B only, which is why they help with movement but aren’t used for depression on their own.
This distinction also matters for side effects. Non-selective MAOIs carry stricter dietary and drug interaction rules because blocking MAO-A in the gut interferes with how your body processes a substance called tyramine in food.
The Tyramine Diet Restriction
Tyramine is a naturally occurring compound found in aged, fermented, and cured foods. Normally, MAO-A in your gut breaks tyramine down before it can affect your blood pressure. When a non-selective MAOI blocks that enzyme, tyramine can build up rapidly and cause a dangerous spike in blood pressure that may require emergency treatment.
Foods you need to avoid while taking a non-selective MAOI include:
- Aged and artisan cheeses: cheddar, Swiss, Parmesan, blue cheeses like Stilton and Gorgonzola, brie, Camembert, feta, Gruyere, and Edam
- Cured meats: pepperoni, salami, dry-type summer sausages, and anything treated with salt and nitrate
- Certain alcoholic drinks: sherry, liqueurs, and some red wines
- Spoiled or improperly stored food: leftovers and anything past its freshness date can develop tyramine as it ages
Caffeinated beverages may also contain tyramine, so your prescriber may recommend limiting coffee and tea intake. The general rule is to eat only fresh foods and avoid anything fermented, aged, or pickled. The selegiline patch at its lowest 6 mg dose is the one exception, as it doesn’t significantly block MAO-A in the gut.
Drug Interactions to Know About
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 accumulating in the brain. Symptoms include agitation, rapid heart rate, high body temperature, and muscle rigidity.
You cannot combine MAOIs with SSRIs (like fluoxetine or sertraline), SNRIs, or most other antidepressants. Many over-the-counter cold and cough medications also pose risks because they contain ingredients that raise serotonin or norepinephrine levels. Even common pain relievers and decongestants can be problematic, so it’s critical to check every medication, including supplements, with your pharmacist.
Switching between an MAOI and another antidepressant requires a washout period of at least 14 days. During this gap, the old drug clears your system before the new one starts. Cross-tapering, where you gradually reduce one while increasing another, is not recommended with MAOIs because the overlap creates too high a risk of serotonin syndrome.
Common Side Effects
The most frequently reported side effect when starting an MAOI is orthostatic hypotension, a drop in blood pressure when you stand up that can cause dizziness or lightheadedness. This usually improves as your body adjusts, and it can be managed by increasing the dose slowly and staying well hydrated. Other early side effects include drowsiness, insomnia, and nausea.
With longer-term use, side effects shift. Weight gain, sexual dysfunction, fluid retention, and muscle aches become more common. Some people experience tingling or prickling sensations in the hands and feet, or involuntary muscle twitches. These side effects are a significant reason MAOIs are kept as a backup option rather than a first treatment, despite their effectiveness for certain types of depression.
Reversible MAOIs
A newer subclass called RIMAs (reversible inhibitors of MAO-A) exists outside the United States. The most well-known is moclobemide, which is available in Canada, the UK, Australia, and parts of Europe. Unlike traditional MAOIs, RIMAs bind to the enzyme temporarily. This means that if tyramine levels spike from food, the drug gets displaced and the enzyme can still do its job. The result is a much lower risk of blood pressure crises and far fewer dietary restrictions. RIMAs are not FDA-approved in the U.S., so American patients don’t have access to them through standard prescriptions.