The antidepressant bupropion may be associated with less weight gain compared with other antidepressants such as fluoxetine or sertraline, according to research published in April 2016 in the Journal of Clinical Medicine.

Obesity rates continue to rise along with rates of antidepressant use, and research suggests that antidepressant medications can influence changes in patients’ weight. Previous findings link certain antidepressants with weight loss, while others were associated with weight gain. The follow-up data on those studies, however, has typically only covered the first 12 months following treatment initiation, and there is limited evidence regarding the long-term influence of antidepressants on weight.

“Still, many patients are prescribed antidepressants for long time periods, and it is important to know whether this longer-term exposure is related to weight gain,” the authors wrote.

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There are several areas of overlap between obesity and depression: Both are significant public health issues, they often co-occur and may pose greater health risks than each alone, and each could increase the risk of the other.

In a 2012 study, an estimated 34.9% of US adults met the criteria for obesity–defined as having a body mass index (BMI) of 30 kg/m2 or more, and other research shows that antidepressants are the most widely prescribed medications in the country, with a 10.4% rate of use among US adults as of 2008. 

Because evidence shows similar efficacy among the most commonly prescribed antidepressants — which are the second-generation antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and selective serotonin norepinephrine reuptake inhibitors (SSNRIs) — they state that prescribing clinicians should consider the impact on weight when choosing an antidepressant for a patient.

“Thus, having more information on the long-term impact of antidepressants on weight could reduce the downstream risk of weight-related morbidity for a large population of adults with depression,” the authors wrote.

In the present study, researchers conducted a retrospective analysis of data from the electronic health records of adult patients beginning monotherapy with a second-generation antidepressant to determine the relationship between the drug and weight gain after 2 years of treatment. They adjusted for potential confounders, including age, gender, smoking status, and history of anxiety disorder, bipolar disorder, sleep disorder, schizophrenia, and schizoaffective disorders.

Additionally, since bupropion is also used to aid smoking cessation, which itself is linked with weight gain, they investigated the effects of that particular drug on weight gain among smokers and non-smokers.

The findings showed that non-smokers who initiated treatment with bupropion had a weight loss of approximately 7.1 pounds compared with fluoxetine users. These results are in line with previous studies linking bupropion with weight loss in both depressed and non-depressed participants. The reason for this association is unclear, though it is believed that bupropion may impact appetite and satiety via its effects on the dopaminergic and noradrenergic systems. No significant difference was found between bupropion and fluoxetine users who were smokers.

Sertraline was also associated with significant weight changes at the 2-year mark: Compared with fluoxetine, patients taking the drug gained approximately 5.9 pounds compared to patients taking fluoxetine.

“Bupropion may be considered as the first-line drug of choice for overweight and obese patients unless there are other existing contraindications,” the authors concluded. These contraindications may include a history of seizure disorder or eating disorders.

“Similarly, in any patients who are underweight, it may be desirable to consider an antidepressant that is associated with weight gain, such as sertraline,” they wrote.


Arterburn D, Sofer T, Boudreau DM, et al. Long-Term Weight Change after Initiating Second-Generation Antidepressants. J Clin Med. 2016; 5(4), 48; doi:10.3390/jcm5040048.