Check out this answer from Consensus:
Weight gain is a significant side effect of many antidepressants, with some drugs posing a higher risk than others. Understanding the mechanisms behind this weight gain and identifying antidepressants with lower risk profiles can help in making informed treatment decisions. Clinicians should consider these factors when prescribing antidepressants, especially for patients at risk of obesity or related health issues.
By carefully selecting antidepressants and monitoring weight changes, it is possible to mitigate this side effect and improve treatment adherence and outcomes for patients.
Antidepressants are a cornerstone in the treatment of major depressive disorder and other psychiatric conditions. However, one of the significant side effects associated with their use is weight gain. This article explores the relationship between antidepressant use and weight gain, summarizing findings from various research studies to provide a comprehensive understanding of this issue.
The Link Between Antidepressants and Weight Gain
Weight gain is a common adverse effect of many psychotropic drugs, including antidepressants. This side effect can lead to discomfort, treatment discontinuation, and increased risk of obesity-related illnesses such as diabetes, hypertension, and coronary heart disease1. The extent of weight gain varies among different antidepressants and individual patient characteristics.
Antidepressants Most Likely to Cause Weight Gain
Several studies have identified specific antidepressants that are more likely to cause weight gain. Tricyclic antidepressants (TCAs) and mirtazapine are frequently associated with significant weight gain. For instance, amitriptyline, mirtazapine, and paroxetine have been shown to have a higher risk of inducing weight gain compared to other antidepressants1 4. A systematic review also highlighted that quetiapine, haloperidol, and olanzapine, among others, could lead to a clinically significant weight gain of 7% or more from baseline2.
Mechanisms Behind Weight Gain
The weight gain associated with antidepressants is believed to be linked to their pharmacodynamic properties. Specifically, the affinity of antidepressants to histamine H1 receptors has been identified as a strong predictor of weight gain. Antidepressants with high anti-histaminergic activity, such as mirtazapine and TCAs, are more likely to cause weight gain3 6. Other receptors, such as 5HT2c, M3-muscarinic, and α1A-adrenergic, also play a role, but their impact is less significant when H1-receptor affinity is considered3.
Antidepressants Less Likely to Cause Weight Gain
Not all antidepressants are associated with weight gain. Some, like bupropion and fluoxetine, have been linked to weight loss or minimal weight gain. Bupropion, in particular, has been noted for its weight-loss effects, making it a preferable option for patients concerned about weight gain1 2 4. Additionally, selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and sertraline are generally associated with less weight gain compared to TCAs and mirtazapine4 8.
Long-Term Effects and Considerations
While short-term studies provide valuable insights, long-term effects of antidepressant use on weight are crucial for a comprehensive understanding. A study utilizing electronic health records found that over a 12-month period, antidepressants like bupropion, amitriptyline, and nortriptyline were associated with a decreased rate of weight gain compared to citalopram10. This suggests that the propensity for weight gain can vary significantly over time and among different antidepressants.