Which antidepressant is most strongly associated with weight gain?

Mirtazapine is the antidepressant most strongly associated with weight gain due to its unique pharmacological profile. It functions as a noradrenergic and specific serotonergic antidepressant (NaSSA), which enhances the release of norepinephrine and serotonin. One of its notable side effects is stimulation of appetite, often leading to increased caloric intake and subsequent weight gain.

In contrast, other antidepressants such as bupropion are more likely to be associated with weight loss or weight neutrality because they can suppress appetite. Sertraline and venlafaxine, while they may cause some weight changes, are generally not as pronounced in weight gain as mirtazapine. Therefore, when considering the profile of antidepressants in relation to weight effects, mirtazapine stands out as the most significant in terms of its association with weight gain.