MAO Inhibitors: Dangerous Interactions with Common Medications

MAO inhibitors, or MAOIs, are one of the oldest classes of antidepressants still in use today-but they’re also among the most dangerous if taken with the wrong medications or foods. While they can be life-changing for people with treatment-resistant depression, a single wrong pill, cough syrup, or even a slice of aged cheese can trigger a medical emergency. This isn’t theoretical. People have died from combinations that seemed harmless at first glance. If you’re on an MAOI-or considering one-you need to know exactly what to avoid.

How MAO Inhibitors Work (And Why That’s Risky)

MAOIs block the enzyme monoamine oxidase, which normally breaks down brain chemicals like serotonin, norepinephrine, and dopamine. By slowing their breakdown, these drugs boost mood. But that same mechanism becomes a liability when other substances enter the picture. The body can’t regulate excess neurotransmitters anymore. That’s when things go wrong.

The two biggest dangers are serotonin syndrome and hypertensive crisis. Serotonin syndrome happens when too much serotonin builds up in your system. Symptoms start mild-shivering, diarrhea, restlessness-but can quickly turn deadly: fever over 106°F, muscle rigidity, seizures, organ failure. Hypertensive crisis is a sudden, extreme spike in blood pressure, often above 200 mmHg. It can cause stroke, heart attack, or brain hemorrhage within minutes.

Medications That Can Kill You When Mixed With MAOIs

Some drugs are absolute no-go zones. These aren’t just "use with caution" warnings-they’re black box alerts from the FDA.

• SSRIs and SNRIs: Fluoxetine (Prozac), sertraline (Zoloft), venlafaxine (Effexor). Combining these with MAOIs can cause serotonin syndrome within hours. You must wait at least 14 days after stopping an SSRI before starting an MAOI. For fluoxetine, wait five weeks-it sticks around in your body way longer than other SSRIs.
• Dextromethorphan: Found in over 100 cough syrups and cold medicines. A single 30mg dose has triggered fatal reactions in people on phenelzine. The FDA issued a warning in 1992. Many people still don’t know this.
• Tramadol, meperidine, methadone: These painkillers are especially dangerous. A 32-year-old man was intubated after taking tramadol while on selegiline. He survived, but many don’t.
• Linezolid: An antibiotic used for stubborn infections. It’s also an MAOI. Taking it with an antidepressant MAOI has caused multiple deaths. Even a few days of overlap can be fatal.
• Phenylephrine: A common decongestant in cold medicines like Sudafed PE. It causes dangerous spikes in blood pressure when mixed with MAOIs.

Even if a drug isn’t listed on your prescription label, check with your pharmacist. Many over-the-counter products contain hidden MAOI-dangers. A 2021 study found that 34% of primary care doctors didn’t realize dextromethorphan was risky.

Supplements and Herbal Products to Avoid

It’s not just prescription drugs. Many supplements are just as dangerous.

• St. John’s Wort: Often marketed as a "natural antidepressant." It boosts serotonin. Combined with MAOIs, it’s a recipe for serotonin syndrome.
• 5-HTP: A supplement that turns into serotonin in your body. One case report described a patient with a blood pressure of 220/110 and a fever of 40.5°C after taking 200mg of 5-HTP with phenelzine.
• SAMe (S-adenosylmethionine): Used for depression and joint pain. It increases serotonin and dopamine. Don’t take it with MAOIs.
• Ginseng: Early case reports from the 1980s linked it to mania and tremors in people on MAOIs. Even if the reaction was partly due to caffeine contamination, the risk isn’t worth it.

Just because something is "natural" doesn’t mean it’s safe. In fact, supplements aren’t regulated like drugs. You have no idea what’s really in them.

Food Risks: The Tyramine Trap

MAOIs also stop your body from breaking down tyramine-a compound found in aged, fermented, or spoiled foods. Normally, tyramine is harmless. With an MAOI, it triggers massive norepinephrine release, crashing your blood pressure control.

Here’s what to avoid:

• Aged cheeses: Cheddar, blue cheese, Parmesan, Swiss-anything aged over 6 months. One ounce can contain 15mg of tyramine. That’s enough to trigger a crisis.
• Cured meats: Pepperoni, salami, pastrami. Even small amounts add up.
• Fermented soy: Soy sauce, miso, tempeh. A tablespoon of soy sauce can have up to 30mg tyramine.
• Tap and draft beer: Bottled beer is usually safe. Draft beer and homebrews can contain 8-20mg per 12oz.
• Red wine: Especially Chianti. A 5oz glass has about 8mg tyramine.

The threshold for a hypertensive crisis is around 10-25mg of tyramine. That’s less than you think. One slice of aged cheese, a splash of soy sauce, or a glass of draft beer can be enough.

One Exception: The Emsam Patch

Not all MAOIs are equally risky. The selegiline patch (Emsam) delivers the drug through the skin, not the gut. At the lowest dose (6mg/24hr), it doesn’t block the enzyme in your intestines-so tyramine from food gets broken down normally.

Studies show patients on this dose can eat aged cheese and drink beer without risk. That’s why it now makes up 68% of all MAOI prescriptions in the U.S. But if you switch to a higher dose (9mg or 12mg), the dietary restrictions come back. Always check your dose with your doctor.

What You Should Do Right Now

If you’re on an MAOI:

1. Check every medication-even vitamins and OTC stuff-with your pharmacist. Don’t assume it’s safe.
2. Carry a wallet card listing your MAOI and all contraindicated drugs. About 78% of psychiatrists now give these to patients.
3. Keep a list of safe alternatives. For pain, use acetaminophen (Tylenol). For colds, try saline nasal spray or guaifenesin (Mucinex) without decongestants.
4. Don’t stop your MAOI suddenly. Tapering must be done under medical supervision.

If you’re not on an MAOI but think you might need one:

• Ask your doctor if you’ve tried at least two other antidepressants first. MAOIs are a last resort for a reason.
• Ask if the Emsam patch is an option. It’s safer and easier to manage.
• Make sure your doctor knows all your medications, supplements, and even your drinking habits.

Why MAOIs Are Still Used

Despite the risks, MAOIs still work when nothing else does. They’re especially effective for atypical depression-where you feel heavy, oversleep, crave carbs, and react strongly to rejection. They also help with panic disorder and social anxiety when SSRIs fail.

They make up less than 1% of all antidepressant prescriptions in the U.S., but 92% of those are written by psychiatrists. Primary care doctors avoid them because the interaction risks are too high to manage without specialized training.

Electronic health records now block prescriptions that combine MAOIs with dangerous drugs. That’s thanks to a 2004 FDA mandate after 19 deaths were linked to these interactions between 1998 and 2003.

Final Warning

There’s no room for guesswork with MAOIs. One mistake can kill you. Even if you’ve been on the drug for years, a new medication, supplement, or even a change in your diet can trigger a crisis. Always check. Always ask. Never assume.

The good news? With strict rules and awareness, MAOIs can be used safely. But safety only comes from knowledge-not luck.

If you’re managing an MAOI, stay informed. Use a pill organizer labeled with your meds. Keep a printed list of contraindicated drugs in your wallet. Tell every doctor, dentist, and pharmacist you see that you’re on an MAOI-even if they don’t ask. Your life depends on it.