Some antidepressants contribute to weight gain more than others, study finds

By Sandee LaMotte, CNN

(CNN) — Antidepressants can be lifesavers for many struggling with so many mental health diagnoses — anxiety, depression, obsessive-compulsive disorder, panic disorder, social phobias and post-traumatic stress disorder. Yet taking these mood-altering substances can lead to an unpleasant side effect for some — weight gain.

While many people never add extra weight, doctors say concerns over additional pounds are a key reason people may be hesitant to start taking an antidepressant for their mental health. Weight gain is also a reason why some stop their medications despite feeling less depressed or anxious while using them.

Now, a new study sheds light on just how much weight gain might occur — on average — while taking eight of the most commonly prescribed antidepressants.

One of the most widely prescribed antidepressants, sertraline, also known by brand names Zoloft and Lustral, was associated with an average gain of nearly 0.5 pounds (0.2 kilograms) at six months. That rose to 3.2 pounds (1.46 kilograms) at 24 months, according to the study.

Using that as a comparison, researchers found people taking escitalopram, known by the brand names Lexapro and Cipralex, had an average 15% increased risk over sertraline of gaining at least 5% of their baseline weight at six months. The risk was 14% for paroxetine, sold under the names Paxil, Aropax, Pexeva, Seroxat, Sereupin and Brisdelle, the study found.

Duloxetine, sold by the brand names Cymbalta, Loxentia and Yentreve, was associated with a 10% increased risk of a patient gaining at least 5% of their baseline weight compared to sertraline, the study said.

A weight gain of 5% or more over baseline is considered clinically significant for health, said lead study author Joshua Petimar, an assistant professor of population medicine at the Harvard Pilgrim Health Care Institute and Harvard Medical School in Boston.

The typical adult gains an average of 1 to 2 pounds per year, which over time, can contribute to obesity. This weight gain can be driven by physical inactivity, stress, poor sleep and poor food choices, such as eating too many ultraprocessed foods, as well as medications, experts say.

Weight gain by pounds

The study, published Monday in the journal Annals of Internal Medicine, used electronic health record prescription and body mass to compare weight gain among more than 183,000 people. Researchers looked at weight at 6 months, 12 months and 24 months for individuals between the ages of 18 and 80 who were starting an antidepressant for the first time.

When analyzing the data by pounds and kilograms of weight gained, people on escitalopram and paroxetine added an average of 1.4 pounds (0.63 kilograms) by six months. By 24 months, weight had risen by 3.6 pounds (1.63 kilograms) for escitalopram and nearly 3 pounds (1.33 kilograms) for paroxetine.

Duloxetine was associated with an average gain of 1.2 pounds (0.55 kilograms) at six months and 1.7 pounds (0.78 kilograms) at 24 months.

“In our study, the average weight at baseline was 84 kg, or about 185 lb,” Petimar said in an email. “This means that in our study, a 5% increase in weight translated on average to a weight gain of 4.2 kg, or about 9 lb.”

However, the study found no significantly higher or lower risk for citalopram, sold as Celexa; fluoxetine, sold as Prozac; or venlafaxine, sold as Effexor, Effexor XR, Vensir, Vencarm, Venlalix and Venlablue, when compared to sertraline.

“We need to remember these are average values; many people won’t gain any weight, while others could gain considerably more,” said Dr. Roy Perlis, associate chief of psychiatric research at Massachusetts General Hospital and professor of psychiatry at Harvard Medical School in Boston, who conducted a similar study in 2014. He was not involved with the new research.

“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,” Perlis said in an email.

Not all patients perceive weight gain negatively, although it is more common for patients to want to avoid weight gain than to seek it when taking an antidepressant, Petimar said. For example, mirtazapine is an antidepressant that is sometimes used in the treatment of eating disorders.

“We didn’t examine mirtazapine in our study because it’s not considered a common front-line medication for new users of antidepressants,” he said.

Weight loss occurred with one drug

One antidepressant contributed to a small amount of weight loss at six months, the study found.

“Bupropion (Wellbutrin and Zyban) on average had a 15% lower risk of gaining a clinically meaningful amount of weight compared to sertraline,” Petimar said.

“Our study didn’t explore reasons why bupropion was associated with less weight gain than other antidepressants, but other studies have similarly concluded that it is associated with less weight gain than other common antidepressants,” he added.

When analyzed by pounds or kilograms lost, people who took bupropion dropped almost one quarter of a pound (0.01 kilograms) at six months, before gaining 1.2 pounds (0.56 kilograms) at 24 months, according to the research.

Why do antidepressants contribute to weight gain? Science doesn’t yet know, Perlis said.

“Remarkably, we don’t know the precise mechanism by which antidepressants contribute to weight changes. Worse, we really don’t know much about who is most likely to gain or lose weight, so we can’t make good predictions in advance,” he said.

One caution, Perlis said, is that some people lose weight when depressed and lose their appetite. “Some of what we’re seeing may be people regaining weight they’d lost as their depression or anxiety improves.”

The best way to manage side effects is to anticipate them, experts say.

“Patients who are concerned about weight gain should have an open and honest conversation with their clinician about their concerns,” Petimar said.

“There are many clinical factors that determine which medication is right for a given patient,” Petimar said. “These include the patient’s clinical symptoms, their medical history, any other drugs that they are already taking, and possible side effects that the patient is concerned about.”

Clinicians have to weigh all of these factors when they decide which is the best course of treatment, he added, while patients can strive to avoid weight gain by following healthy eating habits and exercising regularly.

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