Does trazodone (an antidepressant medication) cause weight gain in adult patients with a history of mental health issues, such as depression or bipolar disorder?

Does Trazodone Cause Weight Gain?

Trazodone is considered weight-neutral and does not cause significant weight gain, making it a favorable choice when weight concerns are present in patients requiring antidepressant therapy. 1

Weight Profile of Trazodone

Trazodone is positioned favorably among antidepressants for its weight-neutral profile, distinctly different from high-risk agents like mirtazapine, paroxetine, and amitriptyline. 1

Clinical Trial Evidence

• In head-to-head comparisons, mirtazapine and paroxetine resulted in significantly higher weight gain than trazodone, establishing trazodone's superior weight profile. 1

• A direct comparison trial showed trazodone-treated patients experienced a mean weight gain of only 1.2 lbs at treatment discontinuation, compared to a 2.5-lb mean weight loss with bupropion. 2

• The FDA drug label reports weight gain occurred in only 1% of trazodone-treated patients in controlled clinical trials, while weight loss occurred in less than 3% of patients. 3

Comparative Context Among Antidepressants

When selecting antidepressants with weight concerns in mind, understanding the risk hierarchy is essential:

Highest Risk for Weight Gain:

• Mirtazapine, lithium, and MAO inhibitors are associated with the most significant weight gain. 1, 4
• Paroxetine carries the highest risk among all SSRIs. 4, 5
• Amitriptyline has the greatest weight gain risk among tricyclic antidepressants. 4

Weight-Neutral Options:

• Trazodone is explicitly categorized as weight-neutral by the American Academy of Sleep Medicine. 1
• Fluoxetine and sertraline cause initial weight loss followed by long-term weight neutrality. 4, 5

Weight Loss Promoting:

• Bupropion is the only antidepressant consistently associated with weight loss through appetite suppression, with 23% of patients losing ≥5 lbs compared to 11% on placebo. 4

Clinical Decision Algorithm

When weight is a significant concern in antidepressant selection:

1. First-line choice: Bupropion (if no contraindications such as seizure disorders or eating disorders exist). 4

2. Second-line choices: Trazodone, fluoxetine, or sertraline for their weight-neutral profiles. 1, 4

3. Avoid: Mirtazapine, paroxetine, amitriptyline, and MAO inhibitors due to high weight gain risk. 1, 4

Additional Adverse Effects to Consider

While trazodone's weight profile is favorable, clinicians should monitor for:

• Most common adverse effects: Somnolence/sedation, headache, dizziness, and dry mouth. 6, 7
• Cardiovascular concerns: Orthostatic hypotension (particularly in elderly patients or those with heart disease), QT prolongation, and rare cardiac arrhythmias. 3, 7
• Rare but serious: Priapism (rare occurrence requiring patient education). 3, 7

Clinical Efficacy Context

Trazodone demonstrates comparable antidepressant efficacy to other drug classes including TCAs, SSRIs, and SNRIs, while offering advantages in treating insomnia symptoms commonly associated with depression. 6, 7 The typical therapeutic dosage ranges from 150-300 mg/day for monotherapy, with lower dosages used in combination strategies. 7