What antidepressants can help with weight gain?

Antidepressants That Promote Weight Gain

Mirtazapine is the most effective antidepressant for promoting weight gain, followed by tricyclic antidepressants (particularly amitriptyline), and among SSRIs, paroxetine carries the highest risk of weight gain. 1, 2

Primary Recommendations for Weight Gain

First-Line: Mirtazapine

• Mirtazapine has the highest risk of weight gain among commonly prescribed antidepressants and is specifically recommended when therapeutic weight gain is desired 1, 2
• In pediatric trials, 49% of mirtazapine-treated patients gained at least 7% body weight compared to only 5.7% on placebo, with mean weight increase of 4 kg versus 1 kg for placebo 3
• The American Geriatrics Society and European Society for Clinical Nutrition and Metabolism specifically note mirtazapine's beneficial role when patients with depression require both antidepressant treatment and weight gain 1
• Particularly useful in clinical scenarios including:
  • Depression with concurrent appetite loss and weight loss 1
  • Short bowel syndrome patients with insufficient oral intake 1
  • Disorders of gut-brain interaction with significant weight loss 1

Second-Line: Tricyclic Antidepressants

• Amitriptyline carries the greatest weight gain risk among all tricyclic antidepressants 2, 4
• Nortriptyline produces moderate weight gain averaging 1.2 kg at 12 weeks (0.44-point BMI increase), with weight gain commencing in the first 6 weeks and continuing throughout 6-month follow-up 5
• Weight gain with tricyclics is dose-related and occurs irrespective of whether weight loss was a symptom of depression 4, 5
• Underweight patients gain the most weight on nortriptyline, while obese patients at baseline do not gain additional weight 5

Third-Line: Paroxetine (SSRI)

• Paroxetine has the highest risk of weight gain among all SSRIs, particularly during long-term treatment 2, 6, 7
• In head-to-head comparisons, paroxetine resulted in higher weight gain than sertraline, trazodone, or venlafaxine 1

Antidepressants to AVOID for Weight Gain Goals

Weight-Neutral Options

• Fluoxetine and sertraline cause initial weight loss followed by long-term weight neutrality 1, 2
• Escitalopram produces minimal weight change, averaging only 0.14 kg (0.05-point BMI increase) over 12 weeks 5
• Vortioxetine is considered weight-neutral 2

Weight-Loss Promoting

• Bupropion is the only antidepressant consistently associated with weight loss rather than weight gain 1, 2, 8
• Clinical trial data shows 23% of bupropion patients lose ≥5 lbs compared to 11% on placebo 2
• FDA-approved for chronic weight management in combination with naltrexone (Contrave) 2

Clinical Decision Algorithm

When therapeutic weight gain is the goal:

1. Start with mirtazapine as first choice due to strongest appetite-stimulating effects and highest weight gain potential 1, 2
2. Consider amitriptyline or nortriptyline if mirtazapine is contraindicated or not tolerated, particularly in underweight patients 2, 4, 5
3. Use paroxetine as third-line if both mirtazapine and tricyclics are unsuitable 2, 7

Important Clinical Caveats

• Weight gain with these antidepressants is usually perceived as an undesired adverse effect by most patients who gain weight, even when it reverses symptomatic weight loss 5
• Weight gain poses risks including reduced insulin sensitivity and can trigger polycystic ovary syndrome in predisposed women 4
• Monoamine oxidase inhibitors (MAOIs) also cause substantial weight gain but are rarely used due to dietary restrictions and drug interactions 2, 6
• Most antidepressant-induced weight gain becomes more evident in long-term treatment and varies greatly depending on individual characteristics 7