Antidepressants and Unintentional Weight Gain

Abstract

Antidepressants remain among the most widely prescribed medications for major depressive disorder and related conditions, yet their therapeutic benefits are often followed up with unwanted metabolic side effects. A growing body of research indicates that selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs) can lead to significant weight gain, raising concerns about long-term adherence and patient health outcomes. This article examines the pharmacological effects of these drug classes, focusing on how their actions on serotonin, norepinephrine, and other neurotransmitter systems can alter appetite, metabolism, and energy balance. Emphasis is given to the role of serotonin in satiety and carbohydrate craving, and the action of norepinephrine in affecting metabolic rate. The biochemistry of depression itself is also considered, since changes in neurotransmitter signaling from disease converge on drug effects in complex fashion. Contemporary clinical research highlights genetic factors of weight gain risk both between and within antidepressant classes, with some drugs, such as bupropion, emerging as weight-neutral alternatives. The discussion summarizes these findings in the perspective of clinical practice, both the challenge patients have in balancing mental health treatment with physical health and the imperative of individualized prescribing. Lastly, the findings underscore the ongoing need for both the creation of antidepressants that do not sacrifice efficacy for adverse metabolic consequences and for clinicians to closely monitor and assist patients in managing both mood and metabolic health.