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Multiple first-line antidepressant medications were broadly linked with weight gain, although bupropion (Wellbutrin) had the least amount of weight change, according to observational data.

In the 24-month study of 183,118 patients, the estimated weight gain was lower for bupropion compared with sertraline (Zoloft) -- the most commonly prescribed antidepressant in the analysis -- at 6 months (difference -0.22 kg, 95% CI -0.33 to -0.12 kg), according to Joshua Petimar, ScD, of Harvard Medical School and Harvard T.H. Chan School of Public Health in Boston, and colleagues.

Bupropion also had lower estimated weight gain at 12 months (difference -0.71 kg, 95% CI -0.87 to -0.55 kg) and 24 months (difference -0.91 kg, 95% CI -1.14 to -0.66 kg) versus sertraline, they reported in the .

The researchers stated that 6-month weight gain was higher for several other common antidepressants when compared with sertraline:

• Escitalopram (Lexapro): difference 0.41 kg (95% CI 0.31-0.52 kg)
• Paroxetine (Brisdelle): difference 0.37 kg (95% CI 0.20-0.54 kg)
• Duloxetine (Cymbalta): difference 0.34 kg (95% CI 0.22-0.44 kg)
• Venlafaxine (Effexor): difference 0.17 kg (95% CI 0.03-0.31 kg)
• Citalopram (Celexa): difference 0.12 kg (95% CI 0.02-0.23 kg)

Fluoxetine (Prozac) had an estimated weight gain that was slightly lower than but similar to sertraline at 6 months (difference -0.07 kg, 95% CI -0.19 to 0.04 kg), they noted.

"Bupropion led to the least amount of weight gain across all time points compared to the other medications," Petimar told 番茄社区app. "The research implies that clinician-specific choice of antidepressant medication could have an effect on their patient's weight. So for clinicians who have concerns about their patient's weight, they can consider these findings when they're prescribing one for the first time."

Medication adherence over follow-up was low in general, the researchers noted. Petimar pointed out that 6-month adherence for bupropion came in at a high of 41% while 6-month adherence with duloxetine was low at 28%. Nonadherence was defined as >1 month passing without medication, according to the researchers.

"Weight gain is an important side effect for a lot of patients, because it's unwanted," Petimar said. "A lot of patients might be reluctant to adhere to their medication if they start taking it, and they notice that they're gaining weight."

Overall, bupropion was associated with a 15% reduced risk of patients gaining at least 5% of their baseline weight at 6 months. Conversely, escitalopram, paroxetine, and duloxetine were all associated with a higher likelihood of gaining at least 5% of their baseline weight at that time point.

Jacob Ballon, MD, MPH, of Stanford University in California, told 番茄社区app these results are "not alarming."

"In fact, weight gain is fairly modest with these drugs," said Ballon, who was not involved in the study. "There may be some people out there for whom it's an issue, so we should be aware of it, but at the end of the day, the magnitude is low enough that it doesn't have to be really a leading factor in the decision for what medicine you choose."

Still, the results reaffirm the existing understanding that antidepressant treatments may lead to weight gain for patients, he said. Ballon warned that healthcare providers shouldn't choose a patient's initial antidepressants based exclusively on these results, but they could certainly be a factor in choosing between two drugs for a patient.

Petimar and colleagues reviewed electronic health record (EHR) data from 8 U.S. health systems that participated in the National Patient-Centered Clinical Research Network. The study included adults who had received an antidepressant medication from July 2010 to December 2019. Patients with initiation of one antidepressant medication were included in the study.

The mean age for all patients was 48.2, mean BMI was 29.4, 65% patients were women, and 79% were white. Approximately 36% of patients were diagnosed with depression and 39% were diagnosed with anxiety.

Among the eight medications, the most common antidepressant started was sertraline (20%), followed by citalopram (16%) and bupropion (15%). Paroxetine was the least common (4%).

The primary outcome was to estimate intention-to-treat effects of 6-month weight gain for each medication versus sertraline. The secondary outcomes were weight changes at 12 and 24 months.

Study limitations included a lack of data on medication dispensing and incomplete data on weight measures across time points.

"I hope that the study will encourage clinicians and their patients to have conversations with one another about weight gain, if they're concerned about weight gain when taking an antidepressant, and that together they can pick a treatment that works best for their symptoms and avoiding any unwanted side effects as much as possible," Petimar said.

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