Weight Gain from Antidepressants: Which Drugs Cause It and How to Stop It

It’s not rare to hear someone say, "I started feeling better on my antidepressant, but I gained 15 pounds." That’s not just bad luck-it’s a well-documented side effect. About 55-65% of people on long-term antidepressant treatment gain weight, according to a 2023 review in PMC. For many, this isn’t just about clothes fitting tighter. It’s about increased risk for diabetes, heart disease, and even relapse into depression because they stop taking their meds to lose weight.

Which Antidepressants Are Most Likely to Make You Gain Weight?

Not all antidepressants affect your weight the same way. Some barely move the needle. Others? They’re practically designed to make you hungry.

Tricyclic antidepressants (TCAs) like amitriptyline, nortriptyline, and imipramine are among the worst offenders. These older drugs work on multiple brain chemicals, including histamine and serotonin, which can turn up your appetite like a dial. Mirtazapine, a tetracyclic antidepressant, is also notorious. It’s often prescribed for people who can’t sleep or eat due to depression-but it frequently leads to big increases in hunger and weight.

Among SSRIs, paroxetine and citalopram stand out. A 2024 Harvard Health study tracked weight changes over two years. People on paroxetine gained an average of 2.9 pounds after 24 months. Citalopram? Around 3.6 pounds. Even escitalopram, often seen as gentler, led to 3.6 pounds of gain over two years.

Here’s the twist: some SSRIs like fluoxetine and sertraline might even cause slight weight loss in the first few months. But after a year? The body adapts. Serotonin receptors slow down. Cravings for carbs kick in. And the scale starts climbing.

Then there’s bupropion. It’s the exception. Unlike other antidepressants, bupropion blocks dopamine and norepinephrine, not serotonin. That means it doesn’t trigger the same hunger signals. In the same Harvard study, people on bupropion lost 0.25 pounds at six months. Even at 24 months, they only gained 1.2 pounds-less than half of what others gained on paroxetine or citalopram.

Why Do Antidepressants Make You Gain Weight?

It’s not just "eating more because you feel better." Though that happens too, the science shows it’s deeper.

When you take an antidepressant, you’re changing how serotonin works in your brain. In the short term, more serotonin can make you feel full faster. But over time, your brain gets used to it. Receptors slow down. Your body starts craving carbs to boost serotonin naturally. That’s why you suddenly want pasta, cookies, or chips-even if you didn’t before.

Some drugs, especially TCAs and mirtazapine, also block histamine receptors. That’s why they make you sleepy. But that same effect increases appetite. Think of it like your brain’s hunger button is stuck on.

There’s also a metabolic angle. Some antidepressants interfere with how your body uses insulin. That means your body stores more fat, even if you eat the same amount. Leptin and ghrelin-the hormones that tell you when you’re full or hungry-get thrown off balance. One study found that people who took antidepressants and then ate a high-fat diet gained way more weight than those who only ate the diet. And the weight stayed on, even after stopping the meds.

Genetics play a role too. If you’re a slow metabolizer of certain drugs (like those with the CYP2C19 gene variant), you might have higher levels of the drug in your system. That increases your risk of side effects, including weight gain.

What About Weight Loss From Depression?

Before you blame the pill, ask yourself: did you lose weight because of depression?

Many people with severe depression lose their appetite. They skip meals. They lose muscle. When they start feeling better, their appetite comes back-and so does the weight. That’s not the drug’s fault. That’s recovery.

That’s why doctors don’t assume every pound gained is from the medication. A 2024 Harvard study noted that some people gain weight because they’re finally eating again after months of not caring. Others gain because the drug changes their metabolism. Both can happen at once.

That’s why tracking your weight before and after starting treatment matters. If you lost 10 pounds from depression and gain back 7, that’s not a drug side effect-it’s healing.

How to Manage Weight Gain Without Stopping Your Medication

The worst thing you can do is quit your antidepressant because you’re gaining weight. Stopping suddenly can trigger withdrawal, anxiety, or even a full relapse. Clinical studies show that people who stop their meds due to weight gain are 30-50% more likely to fall back into depression.

Here’s what actually works:

1. Switch to bupropion. If you’re on paroxetine or citalopram and gaining weight, talk to your doctor about switching to bupropion. It’s the only antidepressant with consistent evidence of neutral or slightly positive weight effects. Many patients report fewer cravings and more energy after the switch.
2. Add metformin. Originally a diabetes drug, metformin improves insulin sensitivity and reduces appetite. Studies show it can cut antidepressant-related weight gain by up to 50%. One trial found people on SSRIs who took metformin lost an average of 5 pounds over six months.
3. Try GLP-1 agonists. Drugs like semaglutide (Ozempic) and liraglutide (Victoza) are now being used off-label for this exact issue. In trials, patients on antidepressants who added a GLP-1 agonist lost 5-7% of their body weight in six months-without worsening their mood.
4. Move more, eat smarter. You don’t need to run a marathon. Just 30 minutes of walking five days a week helps. Focus on protein and fiber. They keep you full longer and stabilize blood sugar. Avoid sugary snacks, even if they’re "comfort foods."
5. Track your food and mood. Use a simple app or notebook. Note when you feel hungrier, what you eat, and your mood. You might see patterns: "I always crave chips after taking my pill at night." That’s information your doctor can use.

When to Talk to Your Doctor

Don’t wait until you’ve gained 20 pounds. If you notice:

• Increased hunger, especially for carbs or sweets
• Feeling sluggish or hungrier than usual after starting the medication
• Weight gain of more than 5% of your body weight in six months
• Difficulty losing weight despite diet and exercise

That’s your cue to have a conversation. Bring the data. Say: "I’ve gained X pounds since starting Y. I’m worried about diabetes risk. Are there alternatives?"

Your doctor might not know about GLP-1 agonists or metformin for this use. But they can look it up. Or refer you to a psychiatrist who specializes in metabolic side effects.

What About Natural Remedies or Supplements?

There’s no supplement proven to block antidepressant-induced weight gain. Green tea extract? Omega-3s? They help with mood or inflammation, but they won’t stop your body from storing fat because of serotonin receptor changes.

Some people try appetite suppressants from the internet. That’s risky. Many interact with antidepressants and can cause dangerous side effects like serotonin syndrome. Stick to science-backed options: metformin, GLP-1 agonists, and lifestyle changes.

Final Thoughts: You Don’t Have to Choose Between Mental Health and Your Body

Antidepressants save lives. But they come with trade-offs. The good news? You don’t have to accept weight gain as inevitable. There are real, evidence-based ways to manage it without giving up your mental health progress.

Whether you’re on paroxetine, mirtazapine, or even bupropion, your weight isn’t just a number. It’s a signal. Listen to it. Talk to your doctor. Adjust your plan. You can feel better emotionally-and physically.