Weighing in on weight gain from antidepressants

If you're struggling with depression, the most important question about taking an antidepressant is whether it will work. But another question on your mind may be whether it will fuel weight gain.

A new study provides some context by suggesting how much weight, on average, people taking one of eight commonly used antidepressants might expect to gain. This insight is valuable, since people with depression often stop taking antidepressants because they don't like the effect on their weight, a Harvard expert says.

"It's important to acknowledge that weight gain is a key reason that some people decide to stop antidepressants, even if they're otherwise working well," says Dr. Roy Perlis, associate chief of psychiatric research at Massachusetts General Hospital. "It's also a reason people may be reluctant to start them in the first place, even if they're quite depressed or anxious."

What did the study look at?

Published July 2024 in Annals of Internal Medicine, the new study drew on data from more than 183,000 people between ages 20 and 80. Their average age was 48, and 65% were women. Most were overweight or obese at the study's start.

The researchers analyzed participants' electronic health records and body mass index. They gauged weight gain or loss at regular intervals — six, 12, and 24 months — after people began taking an antidepressant for the first time.

The study compared the weight-related effects of sertraline (Zoloft) to seven other antidepressant medications:

• escitalopram (Lexapro)
• paroxetine (Paxil)
• duloxetine (Cymbalta)
• citalopram (Celexa)
• fluoxetine (Prozac)
• venlafaxine (Effexor)
• bupropion (Wellbutrin).

What did the research find?

The antidepressants led to the following average weight gain:

• sertraline: Nearly 0.5 pounds at six months; 3.2 pounds at 24 months
• escitalopram: 1.4 pounds at six months; 3.6 pounds at 24 months
• paroxetine: 1.4 pounds at six months; 2.9 pounds at 24 months
• duloxetine: 1.2 pounds at six months; 1.7 pounds at 24 months.

Citalopram, fluoxetine, and venlafaxine didn't confer lower or higher odds of weight gain than Zoloft, the study found. And only bupropion was associated with a small amount of weight loss — 0.25-pounds — at six months. But that trend reversed at 24 months, when bupropion led to an average weight gain of 1.2 pounds.

What does the study tell us?

"Weight gain is common among antidepressant users, even if the amounts gained on average are modest," says Dr. Perlis, who was not involved in this new study. It underscores similar findings from other studies of antidepressants, including research he published with colleagues a decade ago.

"While differences in weight gain for specific antidepressants tend to be small, there are certainly some — like bupropion — that tend to cause less weight gain," he notes.

It's crucial to keep in mind that the study points out average weight gain. Many people taking antidepressants won't gain any weight and others could gain more. "Still, having average values to work with — and seeing that these averages line up well with prior studies — at least lets us give people a sense of what they might expect," he says.

"One caution is that some people lose weight as a result of depression, which can impact appetite," he adds, "so some of what we're seeing may be people regaining weight they'd lost as their depression or anxiety improves."

What additional limitations did the study have?

Other limitations may have shaped the findings. The study was observational, meaning it cannot prove that antidepressants cause weight changes, only that they were linked with them. It wasn't a randomized, controlled trial — considered the gold standard in research — and the participants taking antidepressants weren't compared to a control group not taking the medications.

Additionally, only about one in three participants was still taking their initially prescribed medication six months after the study started. That makes it difficult to link any later weight changes with a specific medication.

"As with any study that's not randomized, we don't know if the differences between medicines could reflect other differences in who gets prescribed these medicines," Dr. Perlis says. "But, for circumstances where a randomized trial is unrealistic, health records can be a helpful way of trying to study side effects and at least generate a partial answer to these important questions."

What else should you consider?

Another thing to consider, if you're taking an antidepressant, is what types of side effects you're willing to tolerate in pursuit of its mood-smoothing benefits.

"The best way to manage side effects is to anticipate them — to have an open conversation with your doctor about the potential risks and how we'll manage them if they occur," Dr. Perlis says.

What can you discuss with your doctor?

If weight gain is a particular concern for you, you may also wish to consider nondrug treatments for depression. They include:

• Cognitive behavioral therapy (CBT), a type of psychotherapy that teaches people to become aware of their thought patterns and adjust them during stressful moments to reframe their thinking.
• Repetitive transcranial magnetic stimulation (rTMS), a brain stimulation therapy that is noninvasive. It uses an electromagnetic coil placed on the scalp to deliver magnetic pulses that stimulate nerve cells to brain regions involved in depression.

"We know that certain kinds of talk therapies, especially cognitive behavioral therapy, can be very effective for treating depression and anxiety disorders," Dr. Perlis says. "Whether people choose talk therapy or antidepressant medications can depend on their preference. It's important to have multiple options."