Marplan Works by Blocking the Enzyme That Breaks Down Your Brain's Mood Chemicals

If you've been prescribed Marplan (Isocarboxazid) — or you're researching it as a treatment option — you've probably heard it called an MAOI. But what does that actually mean? And how does blocking an enzyme help with depression?

This guide explains how Marplan works in plain English, without the med-school jargon.

What Marplan Does in Your Body

The Problem: Your Brain Is Cleaning Up Too Fast

Your brain communicates using chemical messengers called neurotransmitters. Three of the most important ones for mood are:

• Serotonin — helps regulate mood, sleep, and appetite
• Norepinephrine — affects energy, alertness, and focus
• Dopamine — involved in motivation, pleasure, and reward

In depression, these chemicals may not be available in sufficient amounts. Part of the reason? An enzyme called monoamine oxidase (MAO) breaks them down. Think of MAO as a cleanup crew — it sweeps away serotonin, norepinephrine, and dopamine after they've done their job. In depression, this cleanup may be happening too aggressively, leaving too little of these chemicals available.

The Solution: Marplan Stops the Cleanup Crew

Marplan is a non-selective, irreversible inhibitor of monoamine oxidase. Here's what that means in plain English:

• Non-selective: It blocks both types of the MAO enzyme — MAO-A and MAO-B. MAO-A primarily breaks down serotonin and norepinephrine. MAO-B primarily breaks down dopamine. By blocking both, Marplan increases all three neurotransmitters.
• Irreversible: Once Marplan attaches to the MAO enzyme, it permanently disables it. The enzyme can't recover — your body has to make brand-new MAO enzymes to replace the ones Marplan shut down. This is why Marplan's effects last long after you stop taking it.

Here's an analogy: Imagine your brain is a bathtub with the drain open. Serotonin, norepinephrine, and dopamine are the water. Normally, the water drains out (MAO breaks down the neurotransmitters) as fast as the faucet fills it. Marplan plugs the drain. The water level rises — and your mood improves.

Why This Matters for Side Effects

The same mechanism that makes Marplan effective also explains its side effects and risks. MAO doesn't just break down neurotransmitters in your brain — it also breaks down tyramine, a substance found in certain foods. When MAO is blocked, tyramine builds up and can trigger a dangerous spike in blood pressure called a hypertensive crisis. That's why the tyramine-restricted diet is mandatory while taking Marplan.

How Long Does Marplan Take to Work?

Most patients need 3 to 6 weeks to feel the full antidepressant effects of Marplan. Some notice improvement sooner — often in the first 1–2 weeks — but the full therapeutic benefit builds gradually.

Here's why it takes time: even though Marplan starts blocking MAO enzymes right away, it takes weeks for the increased neurotransmitter levels to produce meaningful changes in mood and brain function. Your brain needs time to adapt to the new chemical environment.

During this waiting period, it's important to:

• Keep taking Marplan as prescribed, even if you don't feel different yet
• Attend all follow-up appointments with your psychiatrist
• Report any worsening of depression or new symptoms immediately
• Follow the tyramine-restricted diet from day one

How Long Do Marplan's Effects Last?

Because Marplan irreversibly disables MAO enzymes, its effects don't stop when you stop taking the pill. Your body needs approximately 2 weeks to produce enough new MAO enzymes to restore normal function.

This has two important implications:

1. Dietary restrictions continue after stopping. You must follow the tyramine-restricted diet for at least 2 weeks after your last dose of Marplan.
2. Washout periods before switching medications. If you're switching from Marplan to another antidepressant (especially an SSRI or SNRI), you'll need a 2-week washout period to avoid dangerous interactions like serotonin syndrome.

What Makes Marplan Different From Similar Medications?

Marplan isn't the only MAOI or antidepressant out there. Here's how it compares to the most relevant alternatives:

Marplan vs. Nardil (Phenelzine)

Both are non-selective, irreversible MAOIs in the hydrazine class. They work the same way and have similar dietary restrictions. Nardil is the more commonly prescribed of the two and may be somewhat easier to find. Some patients respond better to one than the other, and the side effect profiles differ slightly — Nardil is more associated with weight gain, while Marplan may have a somewhat better tolerability profile for some patients.

Marplan vs. Parnate (Tranylcypromine)

Parnate is also a non-selective, irreversible MAOI, but it belongs to the non-hydrazine class. It tends to be more activating (less sedating) than Marplan and Nardil. The same dietary restrictions and drug interactions apply. Some psychiatrists prefer Parnate for patients who experience excessive fatigue or sedation with other MAOIs.

Marplan vs. Emsam (Selegiline Transdermal Patch)

Emsam is unique: it's an MAOI delivered through a skin patch. At its lowest dose (6 mg/24 hours), Emsam does not require the tyramine-restricted diet — a major advantage. At higher doses, dietary restrictions kick in. Emsam is selective for MAO-B at low doses but inhibits both MAO-A and MAO-B at higher doses. It's generally better tolerated but may not be as effective for severe, treatment-resistant depression.

Marplan vs. SSRIs and SNRIs

SSRIs (like Sertraline and Fluoxetine) and SNRIs (like Venlafaxine and Duloxetine) work differently — they block the reuptake (reabsorption) of neurotransmitters rather than preventing their breakdown. They're first-line treatments because they have fewer dietary restrictions and drug interactions. However, for patients who don't respond to multiple SSRIs and SNRIs, MAOIs like Marplan can be remarkably effective.

Final Thoughts

Marplan works by permanently shutting down the enzyme that breaks down your brain's mood chemicals. It's a blunt but effective tool — one that increases serotonin, norepinephrine, and dopamine all at once. That broad effect is both its strength (it works when other drugs don't) and its challenge (it requires strict dietary and medication precautions).

Understanding how Marplan works helps you understand why the dietary rules matter, why the washout period exists, and why your doctor monitors you so carefully. If you're taking Marplan and need help finding it in stock, Medfinder can help you locate a pharmacy near you.