Is weight gain a common side effect of Zoloft (sertraline)?

Zoloft and Weight Gain

Sertraline (Zoloft) is associated with initial weight loss followed by weight neutrality during long-term use, making it one of the most weight-favorable SSRIs available. 1, 2

Weight Profile of Sertraline

• Sertraline causes short-term weight loss that transitions to weight neutrality with chronic use, distinguishing it from other SSRIs like paroxetine that consistently promote weight gain. 1

• In pediatric populations (ages 6-17), sertraline produced approximately 1 kg less weight compared to placebo over 10 weeks, representing a slight weight loss versus a slight gain with placebo. 3

• The FDA label documents that approximately 7% of children and 2% of adolescents experienced clinically significant weight loss (>7% of body weight) during sertraline treatment, compared to minimal weight loss in placebo groups. 3

Comparative Positioning Among Antidepressants

When weight concerns are paramount, sertraline ranks among the preferred options, second only to bupropion which is the sole antidepressant consistently associated with weight loss. 1, 2

Best Options (Weight Loss or Neutral):

• Bupropion: Only antidepressant with consistent weight loss through appetite suppression (23% of patients lose ≥5 lbs vs 11% on placebo). 1, 2
• Sertraline and fluoxetine: Initial weight loss transitioning to weight neutrality. 1, 2

Worst Options (Significant Weight Gain):

• Paroxetine: Highest weight gain risk among all SSRIs. 1, 2
• Mirtazapine: Potently promotes sleep, appetite, and weight gain. 1, 2
• Amitriptyline: Greatest weight gain risk among tricyclic antidepressants. 1, 2
• Lithium and MAOIs: Closely associated with substantial weight gain. 1, 2

Clinical Algorithm for Antidepressant Selection Based on Weight Concerns

For patients where weight is a significant concern:

1. First-line choice: Bupropion (if no contraindications such as seizure disorders or eating disorders). 1, 2

2. Second-line choices: Sertraline or fluoxetine for weight-neutral profiles. 1, 2

3. Avoid entirely: Paroxetine, mirtazapine, amitriptyline, and MAOIs. 1, 2

Monitoring Requirements

• Regular weight monitoring is essential if long-term SSRI treatment continues, particularly in pediatric patients where growth and development must be tracked. 3

• The FDA label specifies that subjects initially losing weight on sertraline began gaining weight compared to baseline by week 12 of treatment, though this gain remained similar to age-adjusted peers. 3

• Weight should be monitored at baseline, monthly for the first 3 months, then quarterly during continued treatment. 1

Important Clinical Caveats

• Sertraline's weight effects differ significantly from paroxetine within the same SSRI class, emphasizing that not all SSRIs behave identically regarding metabolic effects. 1

• Weight loss during initial sertraline treatment may represent either symptomatic improvement in patients with depression-related weight loss or a direct medication effect—clinical context determines interpretation. 4

• Sertraline has less effect on metabolism of other medications compared to other SSRIs, making it preferable when polypharmacy is necessary. 1

• The evidence for sertraline's weight neutrality comes from studies ranging from 10 weeks to 52 weeks, with the longest pediatric data showing weight trajectories normalizing to age-appropriate growth curves. 3