Weight Gain Incidence with Mirtazapine
In U.S. controlled clinical trials, 17% of patients experienced increased appetite and 7.5% gained ≥7% of body weight during mirtazapine treatment, compared to 2% and 0% with placebo, respectively. 1
Specific Weight Gain Statistics from Clinical Trials
Adult Populations
- Appetite increase: 17% of mirtazapine-treated patients vs. 2% on placebo 1
- Clinically significant weight gain (≥7% of body weight): 7.5% of mirtazapine-treated patients vs. 0% on placebo 1
- Treatment discontinuation due to weight gain: 8% of patients discontinued mirtazapine in pooled premarketing U.S. studies that included long-term, open-label treatment 1
Pediatric Populations (Higher Risk)
- Weight gain ≥7%: 49% of pediatric patients (ages receiving 15-45 mg/day) vs. 5.7% on placebo in an 8-week trial 1
- Mean weight increase: 4 kg (SD 2 kg) for mirtazapine vs. 1 kg (SD 2 kg) for placebo 1
- This represents a nearly 9-fold higher rate of significant weight gain in pediatric patients compared to adults 1
Elderly Patients with Dementia and Depression
- Proportion experiencing weight gain: Approximately 80% of elderly patients with dementia gained weight on mirtazapine 30 mg daily 2, 3
- Mean weight gain: 1.9 kg at 3 months and 2.1 kg at 6 months 2, 3, 4
- In a retrospective study of 22 elderly patients (mean age 80.9 years), 77.3% gained weight after 3 months (mean 1.93 kg or 3.9% of initial body weight) and 82.3% after 6 months (2.11 kg or 4.6%) 4
Comparative Context Among Antidepressants
Mirtazapine ranks among the highest-risk antidepressants for weight gain, alongside lithium and monoamine oxidase inhibitors. 2, 5
- Mirtazapine causes greater weight gain than most SSRIs (except paroxetine) and most tricyclics (except amitriptyline) 2
- In head-to-head comparisons, mirtazapine and paroxetine resulted in significantly higher weight gain than sertraline, trazodone, or venlafaxine 2
- Bupropion is the only antidepressant consistently associated with weight loss rather than gain 2, 5
Mechanism of Weight Gain
The weight gain occurs through two primary mechanisms:
- Histamine H1 receptor blockade: The most significant contributor to appetite stimulation, with more potent antihistamine effects leading to greater weight gain potential 3
- Serotonin 5-HT3 receptor antagonism: Reduces nausea and early satiety, indirectly promoting increased food intake by removing barriers to eating 3
Critical Clinical Caveats
Exercise extreme caution when prescribing mirtazapine to patients where weight gain would be detrimental, including those with obesity, cardiovascular disease, or metabolic syndrome 3
- Monthly weight monitoring is recommended, with intervention considered for gains >2 kg in a month or ≥7% increase from baseline 2
- The appetite-stimulating effect can be therapeutically beneficial in specific scenarios: depression with concurrent appetite loss/weight loss, elderly patients with dementia and depression, or disorders of gut-brain interaction with significant weight loss 2, 3
- Alternative antidepressants with more favorable weight profiles (bupropion, fluoxetine, or sertraline) should be strongly considered when weight gain risk outweighs therapeutic benefits 2, 5