Can sertraline (Zoloft) cause weight gain?

Sertraline and Weight Effects

Sertraline (Zoloft) is associated with weight loss during short-term use and weight neutrality with long-term use, making it one of the more favorable SSRIs regarding weight effects. 1

Weight Effects of Sertraline Compared to Other Antidepressants

Sertraline's impact on weight varies depending on duration of treatment:

• Short-term effects: Associated with modest weight loss 1, 2
• Long-term effects: Generally weight-neutral 1, 2

When compared to other antidepressants:

• More favorable weight profile than:

  • Paroxetine (significantly higher risk of weight gain) 1, 2
  • Escitalopram (associated with higher weight gain) 3
  • Duloxetine (associated with higher weight gain) 3
  • Tricyclic antidepressants (especially amitriptyline) 1
  • Mirtazapine 1, 4

• Similar weight profile to:

  • Fluoxetine (also associated with initial weight loss and long-term neutrality) 1, 2
  • Citalopram (slightly more weight gain than sertraline) 3

• Less favorable than:

  • Bupropion (the only antidepressant consistently associated with weight loss) 1, 4, 3

Clinical Evidence

A 2024 comparative study found that compared to sertraline, estimated 6-month weight gain was:

• Higher for escitalopram (+0.41 kg), paroxetine (+0.37 kg), duloxetine (+0.34 kg)
• Similar for fluoxetine (-0.07 kg)
• Lower for bupropion (-0.22 kg) 3

An earlier randomized trial found that during extended treatment:

• Paroxetine-treated patients experienced significant weight increase
• Sertraline-treated patients had a modest but non-significant weight increase
• Fluoxetine-treated patients had a modest but non-significant weight decrease 2

Clinical Implications

Patient Selection

• Favorable candidates for sertraline:
  • Patients concerned about weight gain with antidepressant therapy
  • Patients with depression who are overweight or obese
  • Patients with eating disorders where weight gain would be detrimental

Monitoring Recommendations

• Monitor weight regularly during treatment
• Weight loss during initial treatment may be expected and generally not concerning
• If significant weight gain occurs during long-term treatment, consider:
  • Evaluating for other causes of weight gain
  • Possibly switching to bupropion if clinically appropriate 1, 3

Special Considerations

• In pediatric patients, sertraline has been associated with weight loss, with approximately 7% of children experiencing >7% body weight loss compared to none with placebo 5
• For patients with obesity, sertraline may actually enhance weight reduction when combined with cognitive-behavioral treatment 6

Pitfalls and Caveats

• Weight changes with antidepressants are often modest but clinically significant for some patients
• Individual responses vary considerably; some patients may experience weight gain even with medications typically considered weight-neutral
• Medication adherence significantly affects observed weight outcomes (adherence rates in studies range from 28-41%) 3
• Weight changes may be confounded by improvement in depression symptoms (e.g., return of appetite)
• The FDA label for sertraline does not specifically highlight weight gain as a common adverse effect 5

When choosing an antidepressant for patients concerned about weight gain, sertraline represents a reasonable option with a relatively favorable weight profile compared to many alternatives.