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 eating." This isn’t just a personal complaint-it’s a well-documented effect. Around 55 to 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 relapsing into depression because they stop taking their meds.

Why Do Antidepressants Make You Gain Weight?

It’s not one simple reason. Antidepressants change how your brain handles serotonin, dopamine, and other chemicals that control hunger, mood, and energy use. At first, some people actually lose weight because their appetite drops. But after six to twelve months, things flip. Serotonin receptors in your brain get less sensitive. Your body starts craving carbs-especially sugary, starchy foods like bread, pasta, and cookies. That’s not weakness. That’s biology.

Some antidepressants also slow down your metabolism. They interfere with how your body uses glucose and insulin, making it harder to burn calories. Others, like mirtazapine and tricyclics, bind to histamine receptors, which directly triggers hunger. Even your stress hormones play a role. Depression and obesity both mess with the HPA axis-the system that controls cortisol. So when you’re on antidepressants and stressed, your body is primed to store fat.

Which Antidepressants Are Most Likely to Cause Weight Gain?

Not all antidepressants are the same when it comes to weight. Some are nearly neutral. Others are practically guaranteed to add pounds over time.

• High risk: Amitriptyline, nortriptyline, imipramine (tricyclics), mirtazapine (Remeron), paroxetine (Paxil), phenelzine (Nardil)
• Moderate risk: Citalopram (Celexa), escitalopram (Lexapro), sertraline (Zoloft), duloxetine (Cymbalta)
• Lowest risk / weight neutral or loss: Bupropion (Wellbutrin)

A 2024 Harvard Health study tracked weight changes over two years. Here’s what they found:

Weight Gain on Antidepressants Over 24 Months

Medication	Weight Gain at 6 Months	Weight Gain at 24 Months
Bupropion	0.25 lb loss	1.2 lb gain
Sertraline	0.5 lb gain	3.2 lb gain
Escitalopram	1.4 lb gain	3.6 lb gain
Paroxetine	1.4 lb gain	2.9 lb gain
Duloxetine	1.2 lb gain	1.7 lb gain

Bupropion is the only one that consistently leads to weight loss in the first six months. Even after two years, it adds less than half the weight of escitalopram or sertraline. That’s a big difference if you’re trying to avoid metabolic damage.

Is It Really the Medication-or Just Feeling Better?

This is where things get tricky. Many people start antidepressants because they’ve lost their appetite due to depression. They’re not eating. They’re losing weight. When the meds start working, their mood lifts-and so does their appetite. That’s not the drug causing weight gain. That’s their body returning to normal.

A study from the Mayo Clinic points this out clearly: some of the weight gain you see isn’t from the pill. It’s from your brain finally letting you eat again. So before you blame the medication, ask: "Was I eating enough before?" If you were underweight or barely eating, some of the gain is recovery-not side effect.

But if you were eating normally before and now you’re constantly hungry, craving snacks, or gaining weight even though your appetite hasn’t changed, then the drug is likely the main driver.

What Can You Do About It?

Never stop your antidepressant because of weight gain. Stopping suddenly can trigger severe withdrawal, anxiety, or even a return of depression. In fact, studies show that people who quit because of weight gain are 30-50% more likely to relapse.

Instead, talk to your doctor. Here are four proven strategies:

1. Switch to a weight-neutral option - If you’re on paroxetine or mirtazapine and gaining weight, ask about switching to bupropion. It’s not right for everyone (it can raise blood pressure or cause insomnia), but for many, it’s the best alternative.
2. Add metformin - This diabetes drug helps your body use insulin better. Studies show it cuts antidepressant-related weight gain by up to 50%. It’s safe, cheap, and often covered by insurance.
3. Try GLP-1 agonists - Drugs like semaglutide (Wegovy) and liraglutide (Saxenda), originally for diabetes and obesity, are now being used off-label for this exact problem. Clinical trials show patients on antidepressants lost 5-7% of their body weight when added to these drugs.
4. Change your habits - No pill fixes a poor diet. Focus on protein, fiber, and complex carbs. Avoid sugary drinks and processed snacks. Even small changes-like walking 30 minutes a day-can offset metabolic slowdown.

Genetics and Your Risk

Not everyone gains weight on the same drug. Why? Genetics. Some people have a variation in the CYP2C19 gene that affects how quickly their body breaks down certain antidepressants. Slow metabolizers end up with higher drug levels in their blood-meaning more side effects, including weight gain.

If you’ve gained weight on multiple antidepressants, ask your doctor about genetic testing. It’s not routine yet, but it’s becoming more common in mental health clinics. Knowing your metabolism type can help pick the right drug from the start.

What About Long-Term Effects?

Here’s something alarming: research published in Nature suggests that antidepressants might leave a lasting mark on your metabolism-even after you stop taking them. In animal studies, stress combined with antidepressant use, followed by a high-fat diet, led to extreme weight gain long after the drugs were gone.

This doesn’t mean you’ll automatically become obese. But it does mean that if you’ve been on antidepressants for over a year, your body might be more sensitive to weight gain from poor diet or inactivity-even years later. That’s why managing your lifestyle doesn’t end when you stop the medication.

Bottom Line: You Have Options

Weight gain from antidepressants isn’t inevitable. It’s not your fault. And it’s not something you have to live with.

If you’re on a high-risk drug like paroxetine or mirtazapine and gaining weight, talk to your doctor about switching. If you’re on sertraline or escitalopram and seeing slow gains, consider adding metformin. If you’re still unsure, bupropion is your safest bet for avoiding weight gain.

And remember: your mental health matters more than the number on the scale. But you don’t have to choose between feeling better and staying healthy. With the right approach, you can do both.