From the Guidelines
Bupropion is the most appropriate weight-neutral antidepressant option, as it has been consistently shown to promote weight loss and is a first-line treatment for patients concerned about weight gain during depression treatment. According to 1, bupropion is a norepinephrine and dopamine reuptake inhibitor that decreases body weight by suppressing appetite and reducing food cravings. The typical starting dose of bupropion is 150 mg daily for 1 week, then increased to 150 mg twice daily if tolerated, with a maximum dose of 450 mg daily, as seen in 1.
Other weight-neutral options include vortioxetine (Trintellix), starting at 10 mg daily and potentially increasing to 20 mg daily, and some SNRIs like desvenlafaxine (Pristiq, 50 mg daily) and duloxetine (Cymbalta, starting at 30 mg daily and increasing to 60 mg daily). These medications work through different mechanisms - bupropion inhibits norepinephrine and dopamine reuptake, while vortioxetine modulates serotonin receptors and inhibits serotonin reuptake. SNRIs affect both serotonin and norepinephrine systems.
Key points to consider when prescribing weight-neutral antidepressants include:
- Individual responses to medication may vary, and some patients may still experience weight changes even with these typically weight-neutral options.
- Regular monitoring and dose adjustments may be necessary to optimize both mood improvement and minimize side effects.
- The choice of agent must be guided by best practice for the individual patient’s circumstance, taking into account factors such as medical history, current medications, and potential interactions. As noted in 1, it is essential to consider the potential for weight gain with other antidepressants, such as paroxetine and amitriptyline, and to choose alternatives that are weight-neutral or promote weight loss, such as bupropion.
From the Research
Weight Neutral Antidepressants
- Some antidepressants are considered weight neutral, meaning they do not typically cause significant weight gain or loss 2, 3
- Examples of weight neutral antidepressants are not explicitly stated in the provided studies, but it is mentioned that other second-generation antidepressants, excluding bupropion and mirtazapine, are weight neutral but individual variations can occur 3
- Bupropion is an exception, as it has been shown to demonstrate weight-loss effects 2, 4, 5
Antidepressants with Weight Loss Effects
- Bupropion has been found to be effective in promoting weight loss in obese patients 4, 5
- Studies have shown that bupropion can lead to significant weight loss, with one study reporting a mean weight loss of 4.9% over 8 weeks 5
- Bupropion's weight loss effects are thought to be due to its mechanism of action as a norepinephrine and dopamine uptake inhibitor 4
Antidepressants with Weight Gain Effects
- Some antidepressants, such as mirtazapine, have been found to cause significant weight gain 2, 3
- The exact mechanisms of weight gain associated with antidepressants are not fully understood, but it is thought to involve off-target appetite-promoting pathways 2
- Switching to a different antidepressant may be necessary if significant weight gain occurs 3