Note to our followers: Our nearly 13-year run of daily publication of new content on came to a close at the end of 2018. Publisher Gary Schwitzer and other contributors may post new articles periodically. But all of the 6,000+ articles we have published contain lessons to help you improve your critical thinking about health care interventions. And those will be still be alive on the site for a couple of years.
Read Original Release

Best antidepressant for overweight people? Release makes partial case

Research at Group Health points to bupropion (Wellbutrin) as first choice for overweight and obese patients with depression

IMAGE: Dr. Arterburn is a senior investigator at Group Health Research Institute in Seattle. view more

Credit: Group Health Research Institute

SEATTLE–Group Health researchers have found that bupropion (marketed as Wellbutrin) is the only antidepressant that tends to be linked to long-term modest weight loss.

Previously, Group Health researchers showed a two-way street between depression and body weight: People with depression are more likely to be overweight, and vice versa. These researchers also found that most antidepressant medications have been linked to weight gain.

Prior research on antidepressants and weight change was limited to one year or shorter. But many people take antidepressants–the most commonly prescribed medications in the United States–for longer than a year. So for up to two years the new study followed more than 5,000 Group Health patients who started taking an antidepressant. The Journal of Clinical Medicine published it: “Long-Term Weight Change after Initiating Second-Generation Antidepressants.”

“Our study suggests that bupropion is the best initial choice of antidepressant for the vast majority of Americans who have depression and are overweight or obese,” said study leader David Arterburn, MD, MPH. He’s a senior investigator at Group Health Research Institute (GHRI), a Group Health physician, and an affiliate associate professor in the University of Washington (UW) School of Medicine’s Department of Medicine. But in some cases, an overweight or obese patient has reasons why bupropion is not for them–like a history of seizure disorder–and it would be better for them to choose a different treatment option.

Study findings

“We found that bupropion is the only antidepressant that tends to be linked to weight loss over two years,” Dr. Arterburn said. “All other antidepressants are linked to varying degrees of weight gain.”

After two years, nonsmokers lost an average of 2.4 pounds on bupropion–compared with gaining an average of 4.6 pounds on fluoxetine (Prozac). So those who took bupropion ended up weighing 7 pounds less than did those on fluoxetine.

Unsurprisingly, that difference wasn’t seen in people who smoked tobacco. Bupropion is often used to help patients stop smoking. So smokers who take bupropion are likely to be trying to quit–and coping with the weight gain that often accompanies attempts to quit smoking.

Who should try which antidepressant?

“A large body of evidence indicates no difference in how effectively the newer antidepressants improve people’s moods,” said Dr. Arterburn’s coauthor Gregory Simon, MD, MPH, a Group Health psychiatrist, GHRI senior investigator, and research professor in psychiatry and behavioral sciences at the UW School of Medicine. “So it makes sense for doctors and patients to choose antidepressants on the basis of their side effects, costs, and patients’ preferences–and, now, on whether patients are overweight or obese.”

Bupropion should be considered the first-line drug of choice for people who are overweight or obese, Dr. Simon said. But patients should consult their doctor about which medication is right for them, before making any changes, including starting, switching, or stopping medication.


Grant R01 MH083671 from the National Institute of Mental Health funded this research.

Drs. Arterburn and Simon’s coauthors are GHRI Senior Investigator Denise M. Boudreau, PhD, Research Project Management Director Emily O. Westbrook , Programmer Analyst Mary Kay Theis, and Andy Bogart; Tamar Sofer, PhD, a biostatistician at the UW School of Public Health and post-doctoral research fellow at Harvard University; and Sebastien Haneuse, PhD, an associate professor of biostatistics at the Harvard T.H. Chan School of Public Health, who used to work at GHRI.

Group Health Research Institute

Group Health Research Institute does practical research that helps people like you and your family stay healthy. The Institute is the research arm of Seattle-based Group Health Cooperative, a consumer-governed, nonprofit health care system. Founded in 1947, Group Health Cooperative coordinates health care and coverage. The Institute has conducted nonproprietary public-interest research on preventing, diagnosing, and treating major health problems since 1983. Government and private research grants provide its main funding. Follow Group Health research on Twitter, Facebook, Pinterest, LinkedIn, or YouTube.

One antidepressant shown to control weight during 2-year study

Our Review Summary

weight scaleThis news release describes results of a retrospective study by Group Health on the link between antidepressant drugs and weight change over a two-year period in adults with already-diagnosed depression. The results of the study suggest that compared to a “reference” drug, fluoxetine (best known as Prozac), an SSRI or selective serotonin reuptake inhibitor, only bupropion (marketed as Wellbutrin), an NDRI (norepinephrine-dopamine reuptake inhibitor) was associated with modest long-term weight loss and only in non-smokers. The news release doesn’t give us any details on costs or side effects associated with the drugs nor does it tell us how the data was measured or analyzed. It also doesn’t include several limitations of the research included in the published study.

[Editor’s note: Dr. Arterburn, the lead study investigator quoted in the news release, is a former reviewer and contributor to]


Why This Matters

Depression takes a significant toll on human health, well-being and productivity. It’s a challenging condition to treat, costs billions every year worldwide, and suicide is a too-frequent outcome.

Antidepressants are among the mostly commonly prescribed (and heavily marketed) drugs available, and a vast literature about their use suggests there is no particularly significant difference in their effectiveness. All carry some side effects as well. Because many SSRIs have long been linked to weight gain, for obese depressed patients, trying buproprion first might make good sense. Average monthly costs vary widely depending on the availability of generics and doses, and in most cases costs are comparable and covered by insurance, so “differentiators” such as weight issues are not insignificant.


Does the news release adequately discuss the costs of the intervention?

Not Satisfactory

A quote from one of the study’s co-authors mentions “costs” and “patient preferences” as sensible considerations in first choice of antidepressant therapy, but the release offers no information about the comparative costs of the drugs that were studied or even the estimated average annual cost of such therapy. The release would have been strengthened by such data.

Does the news release adequately quantify the benefits of the treatment/test/product/procedure?


The release states that “After two years, nonsmokers lost an average of 2.4 pounds on bupropion–compared with gaining an average of 4.6 pounds on fluoxetine (Prozac). So those who took bupropion ended up weighing 7 pounds less than did those on fluoxetine.”

Does the news release adequately explain/quantify the harms of the intervention?

Not Satisfactory

With the exception of a mention that some people can’t take buproprion (seizure disorder patients, for example), and the weight gain issue, the release makes no mention of the considerable side effects that accompany antidepressant use, or the often frustrating search patients and physicians must undertake to find an antidepressant that is both effective and tolerable for individual patients. Fatigue, insomnia, increased anxiety, headache and nausea are all fairly common when starting an antidepressant.

Does the news release seem to grasp the quality of the evidence?

Not Satisfactory

The release does not make it clear that this is a retrospective study and not one set up to study the effect of antidepressants on weight gain or loss. The published study’s summary offered detailed information about the makeup of the study population and the strengths and weaknesses of the study’s data and analytic approach. Not much of that information was used in the release.

To be helpful to readers, the release should have noted at least some of these limitations that were pointed out in the study:

  • The analysis involved only patients of a single large health plan and that it should be replicated in other systems.
  • The data studied included different data sets. One included a very small number of people actually completing the two years of treatment and another analysis included patients who initiated treatment but didn’t continue the drug for the full two years, “so the estimates of drug effects may be biased.”
  • The changes in weight that were observed were clinically small for all but the bupropion users.
  • Some second-generation antidepressants were not on the Group Health formulary and were excluded from the analyses.
  • Patients who may have taken other drugs including metformin, lisdexamfetamine, topiramate, cyproheptadine, megestrol, or cannabinoid derivatives were not excluded from the study, “Therefore our results should be interpreted with some caution as it is possible that we included some patients who received these medications while not accounting for their potential weight effects.”

Does the news release commit disease-mongering?


The release doesn’t engage in disease mongering. Nor does it give us any context about the prevalence of depression which might have been warranted here.

Does the news release identify funding sources & disclose conflicts of interest?


That’s pretty well covered, with lots of information about Group Health and the grantors.

Does the news release compare the new approach with existing alternatives?


In essence, the purpose of this study was to compare alternatives and report their effect on weight gain or loss. The news release notes that fluoxetine was chosen as the “reference” drug to compare with buproprion. The study suggests that in addition to fluoxetine, the researchers looked at data from patients assigned to a number of other drugs, too, but their data sets were incomplete.

Does the news release establish the availability of the treatment/test/product/procedure?


The release makes clear that all of the antidepressants are available and approved.

Does the news release establish the true novelty of the approach?


The release claims that the study was the first to examine weight gain in people using antidepressants for more than a year, in this case up to two years.

Does the news release include unjustifiable, sensational language, including in the quotes of researchers?


The release doesn’t rely on unjustifiable language. We would underscore the study author’s comment that “bupropion is the best initial choice of antidepressant for the vast majority of Americans who have depression and are overweight or obese” by adding that each individual needs to be evaluated for their symptoms with a medical professional making a recommendation on the appropriate drug therapy.

Total Score: 7 of 10 Satisfactory


Please note, comments are no longer published through this website. All previously made comments are still archived and available for viewing through select posts.