From the Guidelines
Paroxetine is the SSRI most likely to cause weight gain, while fluoxetine and sertraline are generally associated with weight loss or neutrality, especially with short-term use. Among the commonly prescribed SSRIs, paroxetine has been consistently associated with the highest risk of weight gain, particularly with long-term use 1. The weight gain typically develops gradually over months of treatment and can range from modest (1-2 kg) to more significant amounts in some patients.
Key Points to Consider
- The mechanism behind paroxetine's greater propensity for weight gain likely involves its stronger anticholinergic properties and greater affinity for histamine receptors compared to other SSRIs, which can affect appetite regulation and metabolism.
- Paroxetine has more pronounced effects on norepinephrine reuptake at higher doses, which may further contribute to weight changes.
- Patients concerned about weight gain as a side effect might consider alternative SSRIs like fluoxetine or escitalopram, which are generally associated with more neutral effects on weight, especially for long-term treatment.
- Mirtazapine and paroxetine resulted in higher weight gain than sertraline, trazodone, or venlafaxine 1.
Comparison of SSRIs
- Paroxetine: highest risk of weight gain
- Fluoxetine and sertraline: generally associated with weight loss or neutrality, especially with short-term use
- Other SSRIs: variable effects on weight, but generally less pronounced than paroxetine.
Clinical Implications
- When prescribing SSRIs, consider the potential for weight gain, particularly with paroxetine.
- Monitor patients for weight changes and adjust treatment as needed.
- Consider alternative SSRIs or other antidepressants with more favorable weight profiles for patients concerned about weight gain.
From the Research
Weight Gain Associated with SSRIs
The following SSRIs are associated with weight gain:
- Paroxetine is consistently reported to have a higher risk of weight gain compared to other SSRIs 2, 3, 4
- Sertraline may cause a modest but nonsignificant weight increase 4
- Fluoxetine is associated with a modest but nonsignificant weight decrease or no significant effect on body weight 2, 4
Weight Loss Associated with SSRIs
The following SSRIs are associated with weight loss:
- Fluoxetine may cause weight loss, although the effect appears to be limited to the acute phase of treatment 2
- Bupropion is associated with weight-loss effects 3, 5
Comparison of SSRIs
Studies suggest that the risk of weight gain differs depending on which SSRI is used 4, 6.
- Paroxetine is more likely to cause weight gain than fluoxetine and sertraline 4
- Fluoxetine and bupropion may be less likely to cause weight gain than other SSRIs 2, 3
- Citalopram, escitalopram, sertraline, paroxetine, venlafaxine, duloxetine, and mirtazapine are associated with significant weight gain, while fluoxetine is not 6