Cough Suppressants and MAOIs: What You Need to Know About Dextromethorphan Risks

It’s easy to grab a bottle of cough syrup when you’ve got a cold. But if you’re taking an MAOI antidepressant, that simple act could put you in serious danger. Dextromethorphan - the active ingredient in popular brands like Robitussin, Delsym, and NyQuil - is a common cough suppressant. But when mixed with monoamine oxidase inhibitors (MAOIs), it can trigger a life-threatening condition called serotonin syndrome.

Why This Interaction Is So Dangerous

MAOIs like phenelzine (Nardil), tranylcypromine (Parnate), and selegiline (Zelapar) work by blocking the enzyme that breaks down serotonin, dopamine, and norepinephrine in the brain. This helps lift depression, but it also means these chemicals build up. Dextromethorphan doesn’t just suppress coughs - it’s also a weak serotonin reuptake inhibitor. That means it stops serotonin from being reabsorbed, leaving even more of it floating around in your nervous system.

Put them together, and serotonin levels spike dangerously fast. The result? Serotonin syndrome. This isn’t a mild side effect. It’s a medical emergency. Symptoms can show up within 6 to 24 hours after taking both drugs. You might feel agitated, confused, or have a rapid heartbeat. Your muscles could stiffen. You might develop a fever over 104°F. In severe cases, seizures, loss of consciousness, or organ failure can happen.

A 2022 review in the PMC journal found that 2% to 12% of severe serotonin syndrome cases end in death. And this isn’t rare. Between 2010 and 2022, the FDA recorded 237 reported cases linked to dextromethorphan and MAOIs. Nearly half of those patients needed hospital care. One Reddit user on r/MAOI described being hospitalized after taking cough syrup while on selegiline: “I had muscle rigidity, 104°F fever, and couldn’t think straight.”

How the Body Turns a Safe Drug Into a Deadly Mix

It’s not just about serotonin. Your liver uses an enzyme called CYP2D6 to break down dextromethorphan. But many MAOIs - especially older ones - also block this enzyme. That means dextromethorphan doesn’t get cleared from your body like it should. Clinical studies show plasma levels can jump by 300% to 400%. You’re not just getting the normal dose. You’re getting what’s essentially a triple or quadruple dose.

And it gets worse. If you’re taking other medications that also inhibit CYP2D6 - like fluoxetine (Prozac), paroxetine (Paxil), or even some heart drugs like quinidine - the risk multiplies. The Therapeutic Goods Administration of Australia warns that combining dextromethorphan with any of these drugs can lead to hypertensive crisis, hyperpyrexia (dangerously high body temperature), or death.

Who’s at Risk - And Why Most Don’t Realize It

About 1.2 million Americans use MAOIs each year. Many are prescribed for treatment-resistant depression, anxiety, or Parkinson’s. But here’s the problem: most patients don’t know dextromethorphan is in their cough medicine.

A 2019 survey by the American Society of Health-System Pharmacists found that 78% of people on MAOIs didn’t realize common over-the-counter cough syrups contained dextromethorphan. They read “cough suppressant” and assumed it was harmless. They didn’t check the label. They didn’t ask their pharmacist. And they didn’t think about the fact that MAOIs stay in the system for weeks.

Even worse, many dextromethorphan product labels don’t make the warning obvious. A 2021 analysis found only 38% of OTC cough products displayed the MAOI warning in large, clear print. The FDA tried to fix this in 2010 after 27 deaths between 2000 and 2009. But enforcement is still inconsistent.

What to Do If You’re on an MAOI

The rule is simple: do not take dextromethorphan if you’re on an MAOI. Not even once. Not even a teaspoon. The risk isn’t worth it.

And it’s not just about when you take the cough medicine - it’s about when you last took the MAOI. These drugs stick around. The Therapeutic Goods Administration and GoodRx both say you must wait at least 14 days after your last MAOI dose before using dextromethorphan. Some experts recommend waiting longer, especially if you were on a high dose or a long-acting form like the selegiline patch.

Don’t assume your doctor told you. Don’t assume the pharmacist checked. Take responsibility. Before you buy any cold or flu medicine, read the “Active Ingredients” section on the back. Look for “dextromethorphan” - it might be listed as “DM” or “DXM.” If you see it, put it back.

Safe Alternatives for Cough Relief

You don’t have to suffer. There are safe options.

• Guaifenesin (Mucinex) - this thins mucus and helps you cough it up. It doesn’t affect serotonin. Just make sure it doesn’t contain dextromethorphan. Some versions do.
• Honey - studies show honey is as effective as dextromethorphan for nighttime coughs in adults and children over one year old. Try a spoonful before bed.
• Steam and hydration - warm fluids, humidifiers, and saline nasal sprays can ease irritation and reduce coughing.

Even honey needs caution. Some raw honey contains small amounts of tyramine, which can interact with MAOIs and raise blood pressure. Stick to pasteurized honey if you’re unsure.

What to Do If You Accidentally Mix Them

If you took dextromethorphan while on an MAOI - even if you feel fine - monitor yourself closely for the next 24 hours. Watch for:

• Agitation, confusion, or hallucinations
• Fast heartbeat, high blood pressure, or sweating
• Muscle stiffness, twitching, or shivering
• Fever over 101°F
• Nausea, vomiting, or diarrhea

If you have any of these, go to the emergency room immediately. Don’t wait. Don’t call your doctor first. Serotonin syndrome can kill before the drugs leave your system. Treatment requires hospital care - IV fluids, benzodiazepines to calm agitation, and sometimes drugs like cyproheptadine to block serotonin.

One patient on PatientsLikeMe shared: “I didn’t know my nighttime cold medicine had dextromethorphan. Four hours later, I couldn’t speak. ER doctors said I was lucky to survive.”

How Pharmacists Can Help - And Why You Should Ask

Pharmacists are your best defense. A 2021 study showed that when pharmacists actively counseled MAOI patients about OTC risks, accidental dextromethorphan use dropped by 67%. But most people don’t ask.

Next time you pick up your MAOI prescription, ask: “What over-the-counter cold and cough medicines should I avoid?” Show them the label of any OTC medicine you’re thinking of using. They’ll tell you if it’s safe.

And if you’re a caregiver for someone on an MAOI - a parent, spouse, or elderly relative - check their medicine cabinet. Remove anything with dextromethorphan. Put up a reminder note. This isn’t about being overly cautious. It’s about preventing a preventable tragedy.

What’s Changing - And What’s Still at Risk

The FDA proposed stronger warnings for dextromethorphan products in 2022, with new labeling required by late 2024. The European Medicines Agency now requires printed patient guides listing brand names that contain dextromethorphan. Researchers are also finding that newer MAOIs like moclobemide (a reversible inhibitor) carry much lower risk - only one case of serotonin syndrome reported with dextromethorphan, compared to nearly 200 with older types.

But here’s the problem: MAOI use is rising. Since 2020, prescriptions for treatment-resistant depression have gone up 22%. More people are on these drugs. More people are reaching for cough syrup. And fewer than half get proper counseling. The National Alliance on Mental Illness says only 43% of new MAOI patients receive clear warnings about OTC risks.

This isn’t going away. It’s getting worse. And it’s preventable - if you know the risk.