New Study Shows Which Antidepressants May Cause the Most Weight Gain

Weight gain has long been a common side effect of antidepressants, but some of them are more likely to add pounds than others, according to a new study.

The study, published on Monday in the journal Annals of Internal Medicine, analyzed the electronic health records of more than 183,000 U.S. patients who were considered first-time antidepressant users and tracked their weight for 24 months.

After six months, patients who took Lexapro, Paxil or Cymbalta had a higher risk, 10 to 15 percent, of gaining a clinically significant amount of weight, defined as at least 5 percent of their baseline weight, compared with users of Zoloft. Those taking Wellbutrin were less likely to experience this type of weight gain. The study included both the brand name and generic forms of each medication.

“A lot of patients are concerned about gaining excess weight when they’re taking an antidepressant,” said Joshua Petimar, who is an assistant professor of population medicine at Harvard Medical School and the Harvard Pilgrim Health Care Institute, and the lead author of the study. That may be especially true of patients with a pre-existing health condition like diabetes.

In addition, some patients might stop taking their antidepressant — even if it’s effective — because they don’t like that they’ve gained weight. “That also can kind of lead to a host of adverse outcomes like increased risk of hospitalization or relapse of symptoms,” Dr. Petimar said.

In the study, at six months the patients who took Lexapro or Paxil gained about a pound more on average than those who took Zoloft, which was the most commonly prescribed among the eight antidepressants that were tracked. People who took Cymbalta, Effexor or Celexa also initially put on more weight than did users of Zoloft, but in each case it was less than a pound. Those who took Wellbutrin, however, put on less weight than those who took Zoloft.

The study showed some level of weight gain across all of the antidepressants. And most of the people in the study were either overweight or obese at the start, which is representative of the U.S. population.

“It doesn’t matter dramatically which ones you choose,” said Dr. David J. Hellerstein, who is a professor of clinical psychiatry at Columbia University Irving Medical Center and was not involved in the study. “It’s the same problem across the board.”

Picking the right antidepressant can be a balancing act between efficacy and side effects, he added. And deciding which side effects you’re willing to deal with can be difficult.

While Wellbutrin users appear less likely to gain weight, for example, that medication “causes a lot of dry mouth and it has caffeine-like side effects,” Dr. Hellerstein said. “Some people don’t like that.”

It is also difficult to make broad generalizations as to whether a specific antidepressant will cause someone to gain weight, especially given variations in diet and exercise as well as genes and health history, the experts said.

The study had several limitations. The researchers could not verify that each patient was taking an antidepressant for the first time. In addition, the data did not include consistent information about medication dosage, which meant the researchers could not determine how the dosage might affect weight gain.

In addition, some people might have gained weight during the study period even if they had not been using a medication, Dr. Hellerstein said. If the study had included a comparison group of people who were not taking antidepressants then that may have helped determine to what extent the medications contributed to the weight gain, he added.

Given that some medications were associated with a continuous weight change over the two-year study period and that others showed a plateau, further research is needed to know whether these curves can be replicated in a future study, Dr. Petimar said.

“It generates some interesting theories about why the trajectories might be different,” he added.