Marplan Has More Drug Interactions Than Almost Any Other Antidepressant

If you take Marplan (Isocarboxazid) — or you're about to start — you need to know this: Marplan interacts dangerously with a long list of medications, supplements, and foods. Some of these interactions can be life-threatening.

This isn't meant to scare you. It's meant to keep you safe. Marplan is an incredibly effective antidepressant for people with treatment-resistant depression, but it demands careful attention to what else you put in your body. This guide covers every major interaction you need to know about.

How Drug Interactions Work With Marplan

Marplan is a non-selective, irreversible monoamine oxidase inhibitor (MAOI). It blocks the MAO enzyme, which normally breaks down neurotransmitters like serotonin, norepinephrine, and dopamine — as well as other substances like tyramine.

When you take a medication or eat a food that also affects these chemicals, the combination can push your system past safe limits. The two most dangerous results are:

• Hypertensive crisis: A sudden, dangerous spike in blood pressure — potentially causing stroke, brain hemorrhage, or death.
• Serotonin syndrome: An overload of serotonin causing agitation, confusion, rapid heart rate, muscle rigidity, and potentially death.

Both are medical emergencies. Both are preventable if you know what to avoid.

Medications That Interact With Marplan

Major Interactions (Do NOT Combine)

These medications must never be taken with Marplan. In many cases, you also need a washout period of at least 2 weeks between stopping one and starting the other.

Other Antidepressants

• SSRIs: Fluoxetine (Prozac), Sertraline (Zoloft), Paroxetine (Paxil), Citalopram (Celexa), Escitalopram (Lexapro), Fluvoxamine (Luvox) — Risk: serotonin syndrome. Note: Fluoxetine requires a 5-week washout due to its long half-life.
• SNRIs: Venlafaxine (Effexor), Duloxetine (Cymbalta), Desvenlafaxine (Pristiq), Milnacipran (Savella), Levomilnacipran (Fetzima) — Risk: serotonin syndrome.
• Tricyclic antidepressants: Amitriptyline (Elavil), Clomipramine (Anafranil), Imipramine (Tofranil), Nortriptyline (Pamelor) — Risk: hypertensive crisis and serotonin syndrome.
• Other MAOIs: Phenelzine (Nardil), Tranylcypromine (Parnate), Selegiline (Emsam, Eldepryl) — Risk: hypertensive crisis.
• Bupropion (Wellbutrin): — Risk: seizures and hypertensive crisis.

Pain Medications

• Meperidine (Demerol): Potentially fatal interaction. This is one of the most dangerous combinations in all of pharmacology.
• Other opioids: While meperidine is the highest risk, caution is needed with other opioids as well. Your doctor should manage pain medication choices carefully.

Stimulants and Sympathomimetics

• Amphetamines: Adderall, Vyvanse, Dexedrine — Risk: hypertensive crisis.
• Methylphenidate: Ritalin, Concerta — Risk: hypertensive crisis.
• Pseudoephedrine (Sudafed) and Phenylephrine — found in many cold and allergy medications — Risk: hypertensive crisis.

Other Prescription Medications

• Buspirone (Buspar): — Risk: hypertensive crisis.
• Carbamazepine (Tegretol): — Risk: serotonin syndrome and hypertensive crisis.
• Cyclobenzaprine (Flexeril): Structurally similar to tricyclic antidepressants — Risk: serotonin syndrome.
• Levodopa (for Parkinson's) — Risk: hypertensive crisis.
• Methyldopa (for high blood pressure) — Risk: hypertensive crisis.

Moderate Interactions (Use With Caution)

These require careful monitoring and your doctor's guidance:

• Antihypertensives (including Guanethidine) — Marplan can unpredictably alter blood pressure effects.
• Diuretics — May increase risk of low blood pressure.
• CNS depressants: Alcohol, barbiturates, benzodiazepines (Xanax, Valium, Ativan) — increased sedation and respiratory depression.
• Antihistamines — May increase sedation and other side effects.
• General anesthetics — Marplan is contraindicated before elective surgery. Tell your anesthesiologist well in advance.

Supplements and Over-the-Counter Drugs to Watch

Some of the most dangerous interactions are with things you can buy without a prescription:

• Dextromethorphan (DXM): Found in dozens of cough medicines (Robitussin DM, NyQuil, Delsym, Mucinex DM, and many store brands). Check the label of any cough or cold product. If it contains dextromethorphan, do not take it. — Risk: serotonin syndrome.
• Pseudoephedrine and Phenylephrine: Found in Sudafed, many cold medicines, and sinus medications. — Risk: hypertensive crisis.
• Tryptophan supplements (including 5-HTP): — Risk: serotonin syndrome.
• St. John's Wort: A popular herbal supplement for depression — Risk: serotonin syndrome.

The golden rule: Before taking ANY over-the-counter medication, supplement, or herbal product, check with your pharmacist or doctor. This includes cold medicines, allergy medications, sleep aids, and herbal remedies.

Food and Drink Interactions

The tyramine-restricted diet is mandatory while taking Marplan. Tyramine is broken down by the same MAO enzyme that Marplan blocks. Without MAO to process it, tyramine builds up and can cause a hypertensive crisis.

Foods to Avoid

• Aged cheeses: Cheddar, Swiss, Parmesan, Brie, Camembert, Blue cheese, Gouda, Gruyère
• Cured and processed meats: Salami, pepperoni, prosciutto, summer sausage, dried/smoked meats, hot dogs (some), lunch meats (if aged)
• Fermented foods: Sauerkraut, kimchi, miso, tempeh, fermented tofu
• Soy products: Soy sauce, teriyaki sauce, fermented soy bean paste
• Alcoholic beverages: Red wine, tap/draft beer (bottled beer in moderation may be okay — ask your doctor)
• Other: Fava beans, overripe avocados, caviar, pickled herring, canned figs, yeast extracts (Marmite, Vegemite)

Consume in Moderation

• Caffeine: Excessive caffeine can raise blood pressure. Limit to moderate amounts.
• Chocolate: Contains small amounts of tyramine. Small portions are usually fine; avoid large quantities.

These restrictions must continue for at least 2 weeks after stopping Marplan because it takes that long for your body to produce new MAO enzymes.

What to Tell Your Doctor

Before starting Marplan, give your doctor a complete list of:

1. All prescription medications you take — including those prescribed by other doctors
2. All over-the-counter medications — including pain relievers, cold medicines, sleep aids, and allergy medications
3. All supplements and herbal products — including vitamins, minerals, protein powders, and herbal remedies
4. Any recreational substances — including alcohol, cannabis, and others
5. Any planned surgeries or dental procedures — Marplan needs to be stopped at least 10 days before elective surgery requiring general anesthesia

Also tell every healthcare provider you see — including dentists, urgent care doctors, and ER physicians — that you take an MAOI. Consider wearing a medical alert bracelet or carrying a card in your wallet that says you take Marplan.

Final Thoughts

The list of Marplan interactions is long, but it's manageable once you learn it. The key is knowing what to avoid, carrying your "do not take" list with you, and always checking before taking anything new — prescription, OTC, supplement, or food.

Marplan can be a life-changing medication for people with treatment-resistant depression. The interactions aren't a reason to avoid it — they're a reason to be informed and prepared. Work closely with your psychiatrist, follow the rules, and you can take Marplan safely.

Need help finding Marplan in stock? Medfinder can help you locate a pharmacy near you.