Which medication, fluoxetine (Prozac) or vortioxetine (Brintellix), is less associated with weight gain?

Fluoxetine vs Vortioxetine for Weight Gain Concerns

Fluoxetine is less associated with weight gain compared to vortioxetine, with fluoxetine typically causing initial weight loss followed by weight neutrality with long-term use. 1, 2

Comparative Weight Effects

• Fluoxetine is associated with modest weight loss during acute treatment (mean decrease of 0.4 kg in first 4 weeks), followed by weight neutrality with long-term use 3
• Vortioxetine (Trintellix/Brintellix) has been shown to have "no significant effect on body weight" in clinical trials, but is not specifically associated with weight loss 4
• Within the SSRI class, fluoxetine and sertraline are considered more weight-favorable options, while paroxetine has the highest risk of weight gain 1, 2

Evidence Details for Fluoxetine

• In controlled studies, patients taking fluoxetine for 50 weeks showed weight gain similar to placebo after initial weight loss, with the weight gain primarily attributed to recovery from depression rather than medication effect 3
• Fluoxetine has been associated with weight loss with short-term use and weight neutrality with long-term use 5, 1

Evidence Details for Vortioxetine

• According to the FDA label, vortioxetine "had no significant effect on body weight as measured by the mean change from baseline in the 6 to 8 week placebo-controlled studies" 4
• In the six-month, double-blind, placebo-controlled phase of a long-term study, there was "no significant effect on body weight between vortioxetine and placebo-treated patients" 4
• Recent animal research suggests vortioxetine may actually have weight-protective effects in high-fat diet conditions, but this has not been confirmed in humans 6

Clinical Considerations

• Weight gain is a common side effect of many antidepressants and can lead to treatment discontinuation and complications such as type 2 diabetes and cardiovascular disease 6
• For patients with significant concerns about weight gain, bupropion is the only antidepressant consistently shown to promote weight loss through appetite suppression 1, 2
• When choosing between fluoxetine and vortioxetine specifically, fluoxetine offers a slight advantage in terms of weight profile due to its initial weight loss effect 1, 3

Other Considerations

• Vortioxetine may have advantages in other areas, such as procognitive effects and potentially fewer sexual side effects compared to some other antidepressants 7, 8
• Common side effects of vortioxetine include nausea (20.9-31.2%) and vomiting (2.9-6.5%) 8
• Fluoxetine is generally well-tolerated but may have more sexual dysfunction side effects than vortioxetine 7

Caution

• Weight changes with antidepressants are often multifactorial and can be influenced by the patient's recovery from depression 3
• Individual responses to medications vary, and monitoring weight during treatment with any antidepressant is recommended 1