Weight Gain Associated with Remeron (Mirtazapine)
Mirtazapine is closely associated with significant weight gain, with approximately 7.5% of patients gaining ≥7% of body weight in controlled trials, and increased appetite occurring in 17% of patients. 1
Magnitude of Weight Gain
In controlled U.S. clinical studies, 7.5% of mirtazapine-treated patients experienced weight gain of ≥7% of body weight compared to 0% on placebo. 1 The mean weight gain across studies typically ranges from approximately 2-4 kg over treatment periods of several months. 2, 3
- In a retrospective study of patients with Alzheimer's disease, 77.3% gained weight after 3 months (mean gain 1.93 kg or 3.9% of initial body weight) and 82.3% after 6 months (2.11 kg or 4.6%). 3
- In pediatric populations, the effect is even more pronounced: 49% of mirtazapine-treated pediatric patients had weight gain of at least 7%, compared to 5.7% on placebo. 1
Comparative Weight Gain Risk
Among antidepressants, mirtazapine ranks among those with the highest propensity for weight gain, alongside lithium and monoamine oxidase inhibitors. 4
- Mirtazapine causes significantly more weight gain than SSRIs like sertraline, fluoxetine, and bupropion. 4, 2
- Paroxetine and mirtazapine both have higher weight gain potential than other SSRIs, though through different mechanisms. 4, 5
- Bupropion is the only antidepressant consistently associated with weight loss and represents the opposite end of the spectrum from mirtazapine. 4, 5
Mechanism and Associated Effects
The weight gain with mirtazapine occurs through multiple mechanisms: increased appetite (17% of patients), antagonism of histamine H1 receptors, and metabolic effects. 1, 2
- The drug's potent antihistamine properties contribute significantly to weight gain through central H1 receptor antagonism in the hypothalamus. 4
- Increased appetite is reported significantly more frequently with mirtazapine (11%) compared to placebo (2%). 1
- The sedating properties may also contribute indirectly by reducing physical activity. 6
Clinical Monitoring and Management
In premarketing U.S. clinical studies, 8% of patients discontinued mirtazapine specifically due to weight gain. 1
- Weight monitoring should be implemented at baseline and regularly throughout treatment, particularly in the first 3-6 months when weight gain is most pronounced. 1, 3
- The typical dosing range of 15-45 mg daily all carries weight gain risk, though the effect may be dose-related. 4
- For patients with obesity or metabolic concerns, alternative antidepressants with weight-neutral or weight-loss properties (such as bupropion, fluoxetine, or sertraline) should be strongly considered. 4, 5
Additional Metabolic Concerns
Beyond weight gain, mirtazapine is associated with elevated cholesterol (15% of patients with ≥20% increases above normal) and triglycerides (6% with levels ≥500 mg/dL). 1