Side Effects of Mirtazapine
Mirtazapine commonly causes sedation, increased appetite, weight gain, and dizziness as its primary side effects, with sedation being most pronounced at lower doses. 1
Common Side Effects
Neurological Effects
- Sedation/Somnolence: Most prominent side effect, particularly at lower doses (15mg)
- Dizziness
- Headache
- Tremors
Metabolic Effects
- Weight gain: Due to increased appetite
- Increased appetite
- Elevated cholesterol levels (mean 3-4%)
Other Common Side Effects
- Dry mouth
- Constipation
- Edema/fluid retention
Serious but Less Common Side Effects
Hematological
- Low white blood cell count: Can lead to agranulocytosis and neutropenia in rare cases
- Signs include fever, sore throat, flu-like symptoms, mouth sores
Cardiovascular
- Heart rhythm problems
- QT prolongation
Neuropsychiatric
- Serotonin syndrome (when combined with other serotonergic medications)
- Mania/hypomania in patients with bipolar disorder
- Seizures
- Angle-closure glaucoma
Other Serious Concerns
- Severe skin reactions
- Low sodium levels (hyponatremia) - particularly in elderly patients
- Liver function abnormalities
- Discontinuation syndrome if stopped abruptly
Dose-Dependent Effects
Interestingly, sedation is more pronounced at lower doses (7.5-15mg) and may actually decrease at higher doses (30-45mg) 2. This paradoxical effect occurs because:
- At lower doses, mirtazapine primarily blocks histamine H1 receptors
- At higher doses, increased noradrenergic effects counteract some of the sedation
Special Considerations
Elderly Patients
- More sensitive to sedative effects
- Higher risk of hyponatremia
- May experience more pronounced orthostatic hypotension
- Require lower starting doses (7.5mg)
Weight Gain Management
While mirtazapine is sometimes used for appetite stimulation in certain clinical scenarios, weight gain can be significant and problematic 3. The European Society for Clinical Nutrition and Metabolism cautions against using mirtazapine solely for appetite stimulation in elderly patients without depression due to potential risks outweighing benefits.
Discontinuation
- Should not be stopped abruptly
- Gradual tapering over 10-14 days is recommended to limit withdrawal symptoms 2
- Discontinuation symptoms may include dizziness, irritability, anxiety, sweating, and sleep disturbances
Clinical Pearls
- Administer at bedtime to take advantage of sedative effects
- Monitor weight regularly, especially in the first few months of treatment
- The sedative effect may be beneficial for patients with insomnia but problematic for those needing daytime alertness
- Unlike SSRIs, mirtazapine has minimal sexual side effects 4
- Mirtazapine has minimal cardiovascular and anticholinergic effects compared to tricyclic antidepressants 5
Understanding these side effects is crucial for appropriate patient selection, monitoring, and management when prescribing mirtazapine for depression or other approved indications.