Does Mirtazapine Cause More Weight Gain than Zoloft?
Medically reviewed by Linda Girgis | MD, Girgis Family Medicine on August 21st, 2026.
Yes, mirtazapine typically causes significantly more weight gain than Zoloft (sertraline). Clinical studies show mirtazapine causes average weight gain of 3-7 pounds over 6-8 weeks, with some patients gaining 15+ pounds long-term. Zoloft generally causes minimal weight changes, with slight weight loss more common than gain in the first few months. Mirtazapine's weight gain occurs because it blocks histamine H1 receptors and increases appetite, while also affecting metabolism. Zoloft belongs to the SSRI class, which rarely causes significant weight gain and may even suppress appetite initially.
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