Which antidepressants can cause weight loss?

Antidepressants That Cause Weight Loss

Bupropion is the only antidepressant that has been consistently shown to promote weight loss. 1 While most antidepressants are associated with weight gain or weight neutrality, bupropion stands out for its weight-reducing properties.

Antidepressants and Their Effect on Weight

Weight Loss-Promoting Antidepressants:

• Bupropion (Wellbutrin)
  • Consistently promotes weight loss 1, 2
  • Decreases body weight by suppressing appetite and reducing food cravings 1
  • Associated with approximately 2.77 kg weight loss at 6-12 months 1
  • In recent studies, shows 0.22 kg less weight gain compared to sertraline at 6 months 2
  • Associated with 15% reduced risk of gaining at least 5% of baseline weight 2
  • Works as a norepinephrine and dopamine reuptake inhibitor 1
  • FDA-approved for depression and smoking cessation 1

Short-Term Weight Loss, Long-Term Weight Neutral:

• Fluoxetine (Prozac)

  • Associated with weight loss with short-term use (4.74 kg at 6 months) 1
  • Weight neutrality with long-term use (3.15 kg at 12 months) 1
  • Higher doses (60 mg) used for weight loss compared to depression treatment (20 mg) 1

• Sertraline (Zoloft)

  • Associated with weight loss with short-term use 1
  • Weight neutrality with long-term use 1
  • Limited evidence from one small study showing non-significant results 1

Antidepressants Associated with Weight Gain

For context, it's important to understand which antidepressants are most associated with weight gain:

• Significant Weight Gain:

  • Mirtazapine 3, 4
  • Paroxetine (among SSRIs) 1, 2, 4
  • Amitriptyline (among tricyclics) 1, 5, 4
  • Lithium 1
  • Monoamine oxidase inhibitors (MAOIs) 1

• Moderate Weight Gain:

  • Escitalopram (0.41 kg more than sertraline at 6 months) 2
  • Duloxetine (0.34 kg more than sertraline at 6 months) 2
  • Venlafaxine (0.17 kg more than sertraline at 6 months) 2
  • Citalopram (0.12 kg more than sertraline at 6 months) 2

Clinical Considerations When Prescribing Bupropion

Advantages:

• Only antidepressant consistently associated with weight loss 1, 3, 6
• Also FDA-approved for smoking cessation 1
• Part of FDA-approved combination therapy (with naltrexone) for chronic weight management 1

Limitations and Side Effects:

• Not appropriate for all types of depression 1
• Activating effects may exacerbate anxiety 1
• Inappropriate for patients with bipolar disorder 1
• Common side effects include insomnia, dry mouth, headache, nausea, dizziness, and constipation 7
• May cause agitation, anxiety, and increased blood pressure 7
• Contraindicated in patients with seizure disorders 7

Weight Loss Mechanism:

• Suppresses appetite 1
• Reduces food cravings 1
• Affects norepinephrine and dopamine pathways rather than serotonin 1

Clinical Algorithm for Antidepressant Selection When Weight is a Concern

1. For patients where weight loss is desired:

   • First choice: Bupropion (if appropriate for depression type and no contraindications)
   • Alternative: Short-term fluoxetine (recognizing effect may diminish over time)

2. For patients where weight neutrality is desired:

   • Fluoxetine or sertraline for long-term use
   • Consider ziprasidone if antipsychotic properties are needed 1, 8

3. Avoid in patients concerned about weight:

   • Mirtazapine, paroxetine, amitriptyline, lithium, and MAOIs

Important Caveats

• The choice of antidepressant must still be guided by the specific type of depression being treated 1
• Bupropion may not be appropriate for patients with anxiety disorders or bipolar disorder 1
• Weight effects can vary greatly between individuals 4
• Long-term studies (beyond 12 months) are limited for most antidepressants 1
• Medication adherence is generally low across all antidepressants (28-41%) 2

Remember that while weight considerations are important, the primary goal of antidepressant therapy remains effective treatment of depression to reduce morbidity and mortality associated with untreated depression.