Which Selective Serotonin Reuptake Inhibitor (SSRI) is associated with the least amount of weight gain?

From the Guidelines

Selective Serotonin Reuptake Inhibitor (SSRI) with the Least Amount of Weight Gain

Fluoxetine is generally considered the SSRI associated with the least amount of weight gain 1. It is often recommended at a dose of 20mg per day, with a typical treatment duration of at least 6-8 weeks to assess efficacy. Compared to other SSRIs, fluoxetine tends to have a more neutral effect on weight, with some patients even experiencing weight loss 1.

• Key Characteristics of Fluoxetine:
  • Dose: 20mg per day
  • Treatment duration: at least 6-8 weeks
  • Weight effect: neutral, with potential for weight loss
• Comparison to Other SSRIs:
  • Paroxetine and amitriptyline are associated with the greatest risk for weight gain 1
  • Sertraline has been associated with weight loss with short-term use and weight neutrality with long-term use 1
• Important Considerations:
  • Individual responses to medication can vary, and weight changes should be monitored regularly
  • The choice of SSRI should be guided by best practice for the individual patient’s circumstance, taking into account factors such as anxiety, bipolar disorder, and other health conditions 1

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Selective Serotonin Reuptake Inhibitors (SSRIs) and Weight Gain

• The association between SSRIs and weight gain has been studied in several research papers 2, 3, 4, 5.
• According to a study published in 2000, fluoxetine-treated patients had a modest but nonsignificant weight decrease, while paroxetine-treated patients experienced a significant weight increase 2.
• Another study published in 2001 found that fluoxetine reduces food, energy, and carbohydrate intake and increases resting energy expenditure, which may account for the moderate and transient bodyweight loss observed with its use 3.
• A meta-analysis published in 2010 found that fluoxetine was associated with some weight loss, although the effect appears to be limited to the acute phase of treatment 4.
• A prospective comparison between serotonin reuptake inhibitors published in 2004 found that fluoxetine and sertraline were associated with the lowest weight increase, with a higher proportion of clomipramine-treated patients experiencing a significant weight gain 5.

Comparison of SSRIs

• The efficacy of SSRIs has been compared in several studies, with most finding no statistically significant differences between them 6.
• However, differences in clinical characteristics exist between SSRIs, including elimination half-life and potential drug interactions 6.
• Fluoxetine has been found to have a more favorable tolerability profile than other SSRIs, with a lower incidence of weight gain 2, 3, 4, 5.

Weight Gain Risk

• The risk of weight gain during extended SSRI treatment differs depending on which SSRI is used 2, 5.
• Paroxetine and clomipramine have been associated with a higher risk of weight gain, while fluoxetine and sertraline have been associated with a lower risk 2, 5.
• The effect of each antidepressant on body weight may vary greatly depending on an individual's characteristics and generally becomes more evident in the long term 4.