MAOIs: What They Are, How They Work, and What You Need to Know

When we talk about MAOIs, monoamine oxidase inhibitors are a class of antidepressants that block the enzyme monoamine oxidase to increase levels of serotonin, norepinephrine, and dopamine in the brain. Also known as monoamine oxidase inhibitors, they were among the first drugs developed to treat depression—and they’re still used today for cases that don’t respond to newer medications. Unlike SSRIs that target just one neurotransmitter, MAOIs affect multiple brain chemicals at once, which can make them more effective for certain types of depression, especially those with anxiety, panic attacks, or severe fatigue.

But MAOIs come with rules. Because they stop the body from breaking down tyramine—a compound found in aged cheese, cured meats, soy sauce, and red wine—eating these foods while on MAOIs can cause dangerous spikes in blood pressure. That’s why people on these drugs need to follow a strict diet. They also can’t be mixed with many other medications, including common cold remedies, painkillers like tramadol, or even some herbal supplements like St. John’s wort. This makes them harder to use than newer antidepressants, but for some, the trade-off is worth it. Doctors often turn to MAOIs when other treatments have failed, especially for atypical depression, where someone feels heavy limbs, sleeps too much, and craves carbs.

There are different types of MAOIs. Phenelzine and tranylcypromine are older, irreversible versions that stick to the enzyme for weeks. Selegiline comes in a patch form, which lowers the risk of dietary interactions because it doesn’t affect the gut as much. Rasagiline is another patch option, mostly used for Parkinson’s but sometimes prescribed off-label for depression. Each has its own side effect profile—some cause dizziness, weight gain, or trouble sleeping—but many users report a level of emotional relief they didn’t get from other drugs.

MAOIs aren’t a first choice anymore, but they’re not outdated either. They’re a tool in the toolbox, used when everything else has been tried. If you’ve been on multiple antidepressants with little to no improvement, your doctor might suggest an MAOI as a next step. It’s not about being "the best"—it’s about being the one that finally works.

Below, you’ll find real-world guides on how MAOIs fit into broader medication use—from managing drug interactions to understanding why some people respond better than others. These aren’t theoretical articles. They’re written by people who’ve lived with these drugs, worked with them, or helped others navigate their risks and rewards.