Antidepressant medications are the first‐line treatment option for moderate to severe major depressive disorder. However, most antidepressants have numerous documented adverse events, including cardiometabolic effects and weight gain, which are major public health concerns. Antidepressant agents provide varying risk of associated weight gain, including significant within‐class differences. Some agents, such as mirtazapine, show significant levels of weight gain, while others, such as bupropion, demonstrate weight‐loss effects. Current findings suggest the role of histamine and serotonin off‐target appetite‐promoting pathways in adverse weight‐gain effects. Therefore, controlling for undesired weight effects is an important consideration for the selection of antidepressants.
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