The antidepressant bupropion was associated with the least weight gain in patients when compared to other second-generation antidepressants. The findings come from a new study which examined 9 different antidepressants in a group of patients starting monotherapy drug treatment between 2005 and 2009.

The researchers analyzed individual records from the Group Health (GH) integrated health plan and care system in Washington State. A total of 5,932 patients were identified who initiated 6,186 monotherapy antidepressant treatment episodes, of these 1,017 episodes had complete weight data and 2-year weight data; 229 episodes had complete baseline and 2-year weight data and had remained on treatment for two full years.

Fluoxetine was used as reference for the study’s results. In the weighted intent-to-treat (ITT) analyses, non-smokers who initiated bupropion treatment experienced an estimated weight change of –7.1lbs compared to fluoxetine non-smoking users (95% CI: -11.3, -2.8; P<0.01), over 2 years of treatment.

Contrastingly, smokers who initiated bupropion gained 2.2lbs compared to fluoxetine users who smoked (95% CI: -2.3, 6.8;P=0.33).

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Apart from bupropion, the only other medication tied to significant weight change was sertraline, which was associated with a 5.9lbs gain compared to fluoxetine.

Out of the 9 treatments, only non-smoking bupropion users lost weight at 2 years (–2.4lbs). Based on ITT and inverse probability weighted (IPW) analysis the 3 treatments associated with the least weight gain were venlafaxine (2.6lbs), duloxetine (3.6lbs), and non-smoking fluoxetine users (4.6lbs). The greatest weight gain was associated with mirtazapine (16.2lbs), sertraline (10.5bs), and bupropion users who are smokers (6.9lbs).

In the IPW PP weighted analyses, bupropion was the only drug that displayed a significantly different 2 year weight change compared with fluoxetine patients, with non-smokers who initiated bupropion treatment losing an estimated 8.4lbs (95% CI: -16.5, -0.3; P=0.041) compared to non-smoking fluoxetine users.

The study was limited by the small number of individuals who completed the 2 years of treatment in the PP analysis, however the authors are reassured by the fact that the findings in the larger ITT analysis are very similar.

The mechanism of the weight-reducing effect of bupropion has not been determined, though the authors hypothesize that that the dopaminergic and noradrenergic effects of bupropion play important roles in the regulation of appetite, satiety, craving, and feeding behavior.

The authors concluded stating that, “bupropion is the only antidepressant associated with long-term weight loss (although this effect is limited to non-smokers). Given similar efficacy for improvement in depressive symptoms across bupropion and other second-generation antidepressants, bupropion may be considered the first-line drug of choice for overweight and obese patients unless there are other existing contraindications.”

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