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

SSRIs with Lower Risk of Weight Gain

Fluoxetine and sertraline are the SSRIs least likely to cause weight gain, while bupropion (though not an SSRI) is consistently associated with the least weight gain or even weight loss among all antidepressants. 1, 2

Weight Effects of Specific Antidepressants

SSRIs with Favorable Weight Profiles

• Fluoxetine:

  • Associated with weight loss during short-term use and weight neutrality with long-term use 1, 2
  • Shows a modest but nonsignificant weight decrease in long-term studies 3
  • Estimated 6-month weight difference compared to sertraline: -0.07 kg (essentially weight neutral) 4

• Sertraline:

  • Associated with weight loss during short-term use and weight neutrality with long-term use 1, 2
  • Shows a modest but nonsignificant weight increase in long-term treatment 3
  • Used as reference standard in comparative studies 4
  • Has less effect on metabolism of other medications 2

Non-SSRI Option with Best Weight Profile

• Bupropion:
  • Consistently promotes weight loss 1, 2
  • Only antidepressant shown to consistently decrease body weight 1
  • Estimated 6-month weight difference compared to sertraline: -0.22 kg (weight loss) 4
  • Associated with 15% reduced risk of gaining ≥5% of baseline weight 4
  • Works by suppressing appetite and reducing food cravings 1

SSRIs to Avoid When Weight Gain is a Concern

• Paroxetine:

  • Associated with the greatest risk for weight gain within the SSRI class 1, 2
  • Significantly more weight gain compared to fluoxetine or sertraline in long-term studies 3
  • Significantly higher number of patients experiencing >7% weight increase from baseline 3

• Escitalopram:

  • Associated with higher 6-month weight gain compared to sertraline (difference: 0.41 kg) 4
  • 10-15% higher risk for gaining at least 5% of baseline weight 4

Clinical Considerations

Weight Changes During Treatment

• Initial weight loss may occur in the first 4-8 weeks of treatment with fluoxetine and sertraline 5
• Weight changes become more evident with long-term treatment 6
• Weight gain after initial treatment may be related to recovery from depression rather than medication effect 5

Medication Adherence Impact

• Weight gain is an important contributing factor to treatment non-compliance 7
• Six-month adherence rates vary across antidepressants (28-41%), with bupropion showing the highest adherence (41%) 4

Pitfalls and Caveats

1. Individual responses to SSRIs vary significantly 2
2. Not all weight-neutral options are appropriate for all patients with depression 1
3. Bupropion, while excellent for weight management, may be activating and can exacerbate anxiety or be inappropriate for patients with bipolar disorder 1
4. Weight changes during treatment may be influenced by recovery from depression itself 2
5. Weight monitoring should be part of regular follow-up, especially in patients at risk for obesity or related medical conditions 6

Algorithmic Approach to Selecting Weight-Friendly Antidepressants

1. First choice for patients with significant weight concerns:

   • Bupropion (if no contraindications like anxiety disorders or seizure risk) 1, 2

2. Second choices if bupropion is contraindicated:

   • Fluoxetine or sertraline (both weight-neutral with long-term use) 1, 2

3. Avoid when weight gain is a significant concern:

   • Paroxetine (highest weight gain risk among SSRIs) 1, 2, 3
   • Escitalopram (associated with significant weight gain) 4
   • Mirtazapine (promotes appetite and weight gain) 2