What antidepressant options are available that won't cause weight gain for a patient?

Antidepressant Selection to Avoid Weight Gain

Bupropion is the only antidepressant consistently associated with weight loss rather than weight gain and should be your first-line choice when weight concerns are a priority. 1

Primary Recommendation: Bupropion

• Bupropion promotes weight loss through appetite suppression and reduced food cravings, with 23% of patients losing ≥5 lbs compared to only 11% on placebo in long-term trials. 1
• Bupropion is FDA-approved for chronic weight management when combined with naltrexone (Contrave), demonstrating its robust weight-loss effects. 2, 1
• At 300 mg daily, bupropion has proven effective for long-term treatment of recurrent major depression. 2
• The medication works as a dopamine-norepinephrine reuptake inhibitor with no appreciable serotonin activity, distinguishing it from other antidepressants. 3

Critical Contraindications for Bupropion

• Avoid in patients with seizure disorders or eating disorders, as bupropion lowers the seizure threshold. 2, 4
• Do not use in patients requiring opioid therapy, as the naltrexone component in combination formulations can precipitate withdrawal or reduce analgesic efficacy. 2
• Contraindicated within 14 days of monoamine oxidase inhibitor use. 2
• Use caution in patients with uncontrolled hypertension and monitor vital signs regularly. 2

Second-Line Weight-Neutral Options

If bupropion is contraindicated, consider these alternatives:

Fluoxetine (Prozac)

• Fluoxetine causes modest weight loss during initial treatment, followed by weight neutrality with long-term use, making it one of the preferred SSRIs when weight concerns are present. 1
• Ranks among the most weight-favorable SSRIs alongside sertraline. 1

Sertraline (Zoloft)

• Sertraline causes short-term weight loss that transitions to weight neutrality with chronic use. 1
• Has less effect on metabolism of other medications compared to other SSRIs, making it preferable when polypharmacy is necessary. 1

Vortioxetine

• Considered a weight-neutral option by the American Gastroenterological Association. 1
• Works through multiple serotonin receptor mechanisms with improvement in depressive symptoms noted at 2 weeks. 3

Antidepressants to Absolutely Avoid

Highest Risk for Weight Gain

• Paroxetine has the highest risk of weight gain among all SSRIs and should be avoided entirely when weight is a concern. 1, 5
• Mirtazapine is closely associated with significant weight gain and increased appetite through H1 receptor antagonism. 1, 6
• Amitriptyline carries the greatest weight gain risk among tricyclic antidepressants. 1
• Monoamine oxidase inhibitors (MAOIs) cause substantial weight gain. 1

Moderate Risk

• Duloxetine shows higher weight gain than citalopram, though less than paroxetine. 1

Clinical Algorithm for Selection

1. First choice: Bupropion (if no seizure disorder, eating disorder, or opioid requirement) 1
2. Second choice: Sertraline or fluoxetine (for weight-neutral profiles) 1
3. Third choice: Vortioxetine (as alternative weight-neutral option) 1
4. Never use: Paroxetine, mirtazapine, amitriptyline, or MAOIs when weight is a concern 1

Monitoring Requirements

• Regular weight monitoring is essential with long-term SSRI treatment: baseline, monthly for first 3 months, then quarterly during continued treatment. 1
• Monitor vital signs in patients on bupropion, particularly blood pressure. 2
• Observe for neuropsychiatric adverse effects including suicidal thoughts, especially in individuals younger than 24 years. 2

Important Clinical Caveats

• Not all SSRIs behave identically regarding metabolic effects—sertraline's weight profile differs significantly from paroxetine despite being in the same class. 1
• Weight effects can change over time: fluoxetine and sertraline show initial weight loss that transitions to weight neutrality with chronic use. 1, 5
• If a patient fails to lose 5% of total body weight after 12 weeks on naltrexone-bupropion ER at maintenance dose, discontinue as they are likely a poor responder. 2