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

It’s not uncommon to hear someone say, "I started taking antidepressants and suddenly I couldn’t stop gaining weight." For many, this isn’t just about clothes fitting tighter-it’s about fear, confusion, and even guilt. You’re taking medication to feel better, but your body is responding in a way that makes you feel worse. The truth? Antidepressant weight gain is real, common, and often misunderstood. And yes, there are clear ways to manage it without giving up your treatment.

Which antidepressants are most likely to make you gain weight?

Not all antidepressants are the same when it comes to weight. Some barely affect your scale, while others are almost guaranteed to add pounds over time. The biggest culprits? Tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and mirtazapine.

Drugs like amitriptyline, nortriptyline, and imipramine (all TCAs) are known to cause significant weight gain. Mirtazapine, often prescribed for depression with insomnia or poor appetite, is especially notorious-it activates histamine receptors in the brain, which triggers intense hunger, especially for carbs and snacks. Paroxetine (Paxil) and phenelzine (Nardil) also rank high on the list.

Even SSRIs, which are often thought of as "safer" and less likely to cause weight gain, aren’t immune. Sertraline (Zoloft), escitalopram (Lexapro), and citalopram (Celexa) usually don’t cause weight gain in the first few months. But after a year or more, many people start noticing the scale creep up. Why? Because long-term use leads to changes in serotonin receptors that make you crave sugary, starchy foods.

On the flip side, bupropion (Wellbutrin) is the exception. It’s the only commonly prescribed antidepressant that, in the short term, often leads to slight weight loss or at least no gain. Studies show people on bupropion lose about 0.25 pounds at six months. But here’s the catch-even bupropion can lead to a 1.2-pound gain by the two-year mark. Still, that’s far less than the 3.6 pounds seen with escitalopram over the same period.

Why do antidepressants make you gain weight?

It’s not just "eating more because you feel better." While improved mood can lead to a return of appetite (especially if depression had suppressed it), the real issue is biological.

Antidepressants work by changing brain chemicals like serotonin, dopamine, and norepinephrine. But these same chemicals also control hunger, metabolism, and how your body stores fat. Long-term use of many antidepressants causes serotonin receptors in the hypothalamus (the brain’s appetite control center) to become less sensitive. That means your brain stops getting the "I’m full" signal as clearly, leading to more snacking, especially late at night.

Some drugs, like TCAs and mirtazapine, also block histamine receptors, which directly increases appetite. Others affect insulin sensitivity, making your body store more fat instead of burning it. Studies also show changes in leptin and ghrelin-the hormones that tell you when to eat and when to stop. On certain antidepressants, ghrelin (the hunger hormone) rises, while leptin (the fullness hormone) drops.

And it’s not just about what’s happening in your brain. Your metabolism slows down. Some antidepressants interfere with how your body uses glucose, meaning calories are more likely to be stored as fat instead of burned for energy. Even after you stop taking the medication, research suggests these metabolic changes can stick around-especially if you’re eating a high-fat diet.

How much weight do people actually gain?

Numbers matter. If you’re worried, knowing what to expect helps you prepare.

A 2024 Harvard Health study tracked weight changes over two years in people taking common antidepressants. Here’s what they found:

• Escitalopram (Lexapro): 1.4 pounds at 6 months, 3.6 pounds at 24 months
• Paroxetine (Paxil): 1.4 pounds at 6 months, 2.9 pounds at 24 months
• Sertraline (Zoloft): 0.5 pounds at 6 months, 3.2 pounds at 24 months
• Duloxetine (Cymbalta): 1.2 pounds at 6 months, 1.7 pounds at 24 months
• Bupropion (Wellbutrin): -0.25 pounds at 6 months, +1.2 pounds at 24 months

That’s a huge difference-bupropion users gained less than half the weight of those on escitalopram over two years. And while these numbers might seem small, they add up. For someone already at risk for obesity or type 2 diabetes, even a 3- to 4-pound gain can tip the balance.

And here’s the thing: not everyone gains weight. About 35% of people on antidepressants don’t gain any at all. But for the 55-65% who do, the gain is often gradual and hard to notice until it’s too late. That’s why tracking your weight monthly-even if you don’t weigh yourself daily-is a smart habit.

What should you do if you’re gaining weight?

The worst thing you can do is stop your medication on your own. Depression can come back harder than before, and studies show that stopping antidepressants because of weight gain increases relapse risk by 30-50%. That’s why the goal isn’t to quit-it’s to adjust.

1. Talk to your doctor before making any changes. Your mental health matters more than the number on the scale. But that doesn’t mean you have to accept weight gain as inevitable. There are three main strategies:

1. Switch to a different antidepressant. If you’re on paroxetine or mirtazapine and gaining weight, ask about switching to bupropion. It’s not perfect for everyone-some people get jittery or have trouble sleeping on it-but for those who tolerate it, the metabolic benefit is clear.
2. Add a weight-management medication. Metformin, a diabetes drug, has been shown in studies to reduce antidepressant-related weight gain by improving insulin sensitivity. GLP-1 receptor agonists like semaglutide (Ozempic) are now being studied for this exact use. Early trials show patients on these drugs lose 5-7% of their body weight while staying on their antidepressants.
3. Change your lifestyle. Medication helps, but so does movement and food. Focus on protein-rich meals, fiber, and whole foods. Avoid sugary snacks and processed carbs-they trigger cravings when serotonin receptors are downregulated. Aim for at least 150 minutes of moderate exercise a week. Walking counts. Strength training helps, too, because muscle burns more calories at rest.

Some people find that timing matters. If you’re on an SSRI and started gaining weight after six months, it might be worth trying a short-term switch to bupropion during the maintenance phase, then switching back if needed. This isn’t for everyone, but it’s an option your doctor might not have mentioned unless you brought it up.

Is it the medication-or just feeling better?

This is a big one. Many people who gain weight on antidepressants were underweight or had lost their appetite due to depression. When the medication works, their hunger returns. That’s not a side effect-that’s recovery.

So how do you tell the difference? Track your habits. Did your food choices change? Are you eating more snacks because you’re bored, stressed, or emotionally eating? Or are you just eating regular meals again because your appetite came back? Keep a simple food journal for two weeks. Note what you eat, when, and how you felt before and after.

If you’re eating three balanced meals a day and feeling full without snacking, the weight gain is likely just your body returning to normal. But if you’re eating late at night, craving chips or cookies, or eating more than usual even when you’re not hungry-that’s probably the medication.

What about genetics?

Not everyone reacts the same way. Why? Genetics play a role. Some people have variations in the CYP2C19 gene, which affects how quickly their body breaks down certain antidepressants. If you’re a slow metabolizer, you’ll have higher levels of the drug in your system, which can increase side effects-including weight gain.

Pharmacogenetic testing (a simple saliva test) can tell you if you’re at higher risk for side effects from specific antidepressants. It’s not covered by all insurance, but if you’ve tried multiple meds and kept having problems, it’s worth asking about. It’s not magic, but it can save you months of trial and error.

What’s the long-term risk?

Weight gain from antidepressants isn’t just about appearance. It increases your risk for type 2 diabetes, high blood pressure, and heart disease. And since depression itself already raises those risks, you’re dealing with a double burden.

Research suggests that the combination of long-term antidepressant use and a high-fat diet can lead to metabolic changes that persist even after you stop taking the medication. That means the damage doesn’t just go away when you switch drugs. You need to actively reverse it.

That’s why managing weight gain isn’t optional-it’s part of your treatment plan. Just like you monitor your mood, you should monitor your weight, waist size, and blood sugar if you’re on long-term antidepressants.

Final thoughts: You’re not alone, and you’re not failing

Weight gain on antidepressants is not a personal failure. It’s a biological side effect of a powerful class of drugs. Millions of people experience it. The fact that you’re asking this question means you’re already taking control.

Don’t let fear of weight gain keep you from getting the mental health care you need. But don’t ignore it either. Work with your doctor. Track your progress. Consider alternatives. Add movement. Eat mindfully. Use science, not guilt, to guide your choices.

You’re not just treating depression-you’re protecting your whole body. And that’s worth the effort.