What selective serotonin reuptake inhibitors (SSRIs) are less likely to cause weight gain?

SSRIs Less Likely to Cause Weight Gain

Fluoxetine, sertraline, and bupropion are the antidepressants least likely to cause weight gain, with bupropion consistently showing the least weight gain among all options. 1, 2

Weight Impact of Different SSRIs

Weight-Neutral or Weight-Loss Promoting SSRIs:

• Fluoxetine (Prozac): Associated with weight loss during short-term use and weight neutrality with long-term use 1
• Sertraline (Zoloft): Associated with weight loss during short-term use and weight neutrality with long-term use 1
• Bupropion (Wellbutrin): The only antidepressant consistently shown to promote weight loss 1, 2
  • In a recent large-scale study comparing 8 first-line antidepressants, bupropion showed the least weight gain and was associated with a 15% reduced risk of gaining at least 5% of baseline weight 2

SSRIs Associated with Weight Gain:

• Paroxetine (Paxil): Associated with the greatest risk for weight gain within the SSRI class 1, 2
• Escitalopram (Lexapro): Associated with higher weight gain compared to sertraline 2
• Citalopram (Celexa): Shows modest weight gain compared to sertraline 2

Comparative Weight Changes

When compared with sertraline as a reference, estimated 6-month weight differences were 2:

• Bupropion: -0.22 kg (weight loss)
• Fluoxetine: -0.07 kg (essentially weight neutral)
• Sertraline: reference
• Citalopram: +0.12 kg
• Venlafaxine: +0.17 kg
• Duloxetine: +0.34 kg
• Paroxetine: +0.37 kg
• Escitalopram: +0.41 kg

Mechanism and Clinical Considerations

• Initial weight effects: Fluoxetine may cause modest weight loss (approximately 0.4 kg) during the first 4 weeks of therapy 3
• Long-term effects: After remission of depressive symptoms, weight changes with fluoxetine are similar to placebo, suggesting that long-term weight changes may be more related to recovery from depression than medication effects 3
• Drug interactions: When considering SSRIs, note that citalopram and sertraline have the most favorable profile regarding drug interactions 4, which may be relevant for patients on multiple medications

Algorithm for SSRI Selection Based on Weight Concerns

1. First choice: Bupropion (Wellbutrin) - consistently associated with the least weight gain or even weight loss 1, 2

   • Best for patients with significant weight concerns
   • Activating effects make it unsuitable for patients with anxiety or bipolar disorder 1

2. Second choices: Fluoxetine (Prozac) or Sertraline (Zoloft)

   • Weight neutral with long-term use 1
   • Sertraline has less effect on metabolism of other medications 1
   • Fluoxetine has a very long half-life; side effects may not manifest for a few weeks 1

3. Avoid if weight gain is a significant concern:

   • Paroxetine (Paxil) - most weight-promoting SSRI 1, 2
   • Escitalopram (Lexapro) - associated with significant weight gain 2
   • Mirtazapine (Remeron) - promotes appetite and weight gain 1

Important Caveats

• Individual responses to SSRIs vary significantly
• Weight changes may be influenced by recovery from depression itself
• Medication adherence is a significant factor - adherence rates range from 28% to 41% across antidepressants 2
• For patients with psychiatric diagnoses, the choice of agent must still be guided by the specific type of depression, as not all weight-neutral options are appropriate for all patients 1