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." For many, this isn’t just a joke-it’s a real, frustrating, and sometimes scary change. Weight gain from antidepressants isn’t rare. In fact, 55% to 65% of people on long-term treatment report gaining weight, according to a 2023 review in PMC. And while the average gain might seem small-just a few pounds over two years-it’s often enough to make people quit their medication. That’s dangerous. Stopping antidepressants without medical guidance increases the risk of depression returning by 30% to 50%.

Why Do Antidepressants Make You Gain Weight?

It’s not just about eating more. Antidepressants affect your brain chemistry in ways that go far beyond mood. They change how your body handles hunger, metabolism, and even how it stores fat.

Most antidepressants work by increasing serotonin in the brain. In the short term, that can actually reduce appetite. You feel full faster. But after six to twelve months, your brain starts adapting. Serotonin receptors become less sensitive. That’s when cravings kick in-especially for carbs and sugary foods. Your brain is trying to compensate for the changed chemistry, and food becomes a quick fix.

Some drugs also mess with other systems. Tricyclic antidepressants like amitriptyline and nortriptyline, and the drug mirtazapine, block histamine receptors. That’s why people on these meds often feel hungrier and more tired. Slower metabolism? Check. Increased appetite? Double check.

Then there’s insulin. Some antidepressants make your body less responsive to insulin, meaning sugar stays in your blood longer and gets stored as fat. Leptin and ghrelin-the hormones that tell you when you’re full or hungry-also get thrown off balance. And if you’re genetically a slow metabolizer of certain drugs (CYP2C19 gene), your risk goes up even more.

Which Antidepressants Are Most Likely to Cause Weight Gain?

Not all antidepressants are the same when it comes to weight. Some are practically neutral. Others? Not so much.

High-risk drugs:

• Mirtazapine (Remeron) - Known for causing the most weight gain. Patients often gain 5-10 pounds in the first few months.
• Amitriptyline (Elavil) - A tricyclic antidepressant. Strong effect on histamine and serotonin, high chance of weight gain.
• Nortriptyline (Pamelor) - Similar to amitriptyline, slightly less intense but still risky.
• Paroxetine (Paxil) - An SSRI that stands out for weight gain. Even though most SSRIs are neutral early on, paroxetine is an exception.
• Citalopram (Celexa) - Can cause moderate weight gain over time, especially after a year.
• Phenelzine (Nardil) - An MAOI. Rarely used now, but when it is, weight gain is common.

Lower-risk or neutral options:

• Bupropion (Wellbutrin) - The only antidepressant consistently linked to weight loss or no change. It works on dopamine and norepinephrine, not serotonin, so it doesn’t trigger the same cravings.
• Sertraline (Zoloft) - On average, people gain about 3.2 pounds after two years. Not zero, but manageable.
• Escitalopram (Lexapro) - Around 3.6 pounds at 24 months. Similar to sertraline.
• Duloxetine (Cymbalta) - Only 1.7 pounds at two years. One of the lighter options.
• Fluoxetine (Prozac) - Often causes initial weight loss, but after a year, it levels out. Some gain back what they lost.

Here’s the thing: you’re not alone if you’ve gained weight. But you also don’t have to accept it as inevitable.

What If You’re Already Gaining Weight?

Don’t panic. Don’t quit. Talk to your doctor.

Stopping your antidepressant because of weight gain is one of the biggest mistakes people make. Depression comes back faster than the weight does. And when it does, it’s harder to treat.

Instead, here’s what actually works:

1. Switch to a weight-neutral drug - If you’re on mirtazapine or paroxetine and gaining weight, ask about switching to bupropion or sertraline. Many people successfully make the switch without losing their mood gains.
2. Add metformin - Originally for type 2 diabetes, metformin helps improve insulin sensitivity. Studies show it can reduce or even reverse antidepressant-related weight gain. It’s safe, cheap, and often covered by insurance.
3. Try GLP-1 agonists - Drugs like semaglutide (Wegovy) and liraglutide (Saxenda) are now being used off-label for this exact problem. Clinical trials show patients on antidepressants lost 5-7% of their body weight when adding these drugs. Yes, they’re expensive, but some insurance plans cover them now if you have metabolic issues.
4. Focus on protein and fiber - High-protein meals keep you full longer. Fiber slows digestion and stabilizes blood sugar. That means fewer cravings. Swap out white bread for whole grains, chips for nuts, soda for sparkling water with lemon.
5. Movement matters more than you think - You don’t need to run marathons. Just 30 minutes of walking five days a week helps reset your metabolism. Strength training twice a week builds muscle, which burns more calories at rest.

And yes-sleep and stress matter too. Poor sleep raises cortisol, which increases belly fat. Chronic stress makes your body hold onto weight. If your antidepressant isn’t helping your anxiety, you’re stuck in a loop.

Is It Really the Medication-or Just Feeling Better?

This is a big one. Many people lose weight when they’re depressed. They don’t eat. They lose interest in food. When the antidepressant starts working, their appetite comes back. Suddenly, they’re eating like they used to. That’s not the drug making them gain weight-that’s their body returning to normal.

That’s why doctors look at patterns. Did you gain weight before you started the drug? Did you lose weight during your worst depression? Are you eating more because you’re hungry-or because you’re bored, stressed, or emotionally eating?

It’s rarely just one thing. It’s the drug, yes-but also your recovery, your habits, your stress levels, your sleep, your genetics. That’s why a one-size-fits-all approach doesn’t work.

What About Bupropion? Is It the Answer?

Bupropion is the outlier. It’s the only antidepressant that doesn’t increase serotonin. Instead, it boosts dopamine and norepinephrine. That means no serotonin receptor downregulation. No carb cravings. No insulin spikes.

Studies show people on bupropion lose 0.25 pounds at six months. At two years? They gain 1.2 pounds-far less than the 3-4 pounds others gain. For someone who’s overweight or has prediabetes, that difference matters.

But bupropion isn’t perfect. It can cause insomnia or anxiety in some people. It’s not ideal if you have a seizure disorder. And it doesn’t work as well for everyone with depression, especially those with severe anxiety.

Still, if weight is a major concern-and you’re not at high risk for seizures or agitation-it’s often the best first choice.

What You Should Do Next

Here’s a simple action plan:

1. Track your weight and eating habits - For two weeks, write down what you eat and how you feel. Don’t judge. Just observe.
2. Check your medication - Is it one of the high-risk ones? If yes, don’t panic, but start a conversation with your doctor.
3. Ask about alternatives - Can you switch to bupropion? Sertraline? Duloxetine? What are the pros and cons?
4. Request a metabolic check - Ask for fasting glucose and insulin levels. If they’re high, metformin might be an option.
5. Start small with movement - Walk after dinner. Take the stairs. Park farther away. These tiny changes add up.

Weight gain from antidepressants isn’t a personal failure. It’s a biological side effect. And like any side effect, it can be managed-with the right information, the right support, and the right plan.