Optimal Dose of Mirtazapine for Appetite Stimulation
The optimal dose of mirtazapine for appetite stimulation is 15 mg daily, administered at bedtime, as this lower dose maximizes the antihistaminergic effects that drive appetite stimulation while minimizing other dose-dependent effects.
Mechanism of Action for Appetite Stimulation
- Mirtazapine's appetite-stimulating effect is primarily due to its potent antagonism of histamine H1 receptors, which is most pronounced at lower doses (15 mg) 1, 2
- At higher doses (30-45 mg), mirtazapine's noradrenergic and serotonergic effects become more prominent, which can partially counteract the appetite-stimulating effects seen at lower doses 3, 4
- Mirtazapine blocks central α2-adrenergic auto- and heteroreceptors and has high affinity for serotonin 5-HT2 and 5-HT3 receptors, contributing to its unique pharmacological profile 1
Evidence for Dosing
- A retrospective study in patients with dementia given 30 mg mirtazapine daily showed a mean weight gain of 1.9 kg after three months and 2.1 kg after six months, with approximately 80% of patients experiencing weight gain 5
- Lower doses (15 mg) have been shown to produce more sedation and appetite stimulation than higher doses due to the predominance of antihistaminergic effects at this dose range 1, 2
- Clinical data shows that increased appetite (11% vs 2% with placebo) and weight gain (10% vs 1% with placebo) are common side effects of mirtazapine, particularly at lower doses 1
Clinical Application
- For appetite stimulation specifically (rather than depression treatment), start with 15 mg once daily at bedtime 3, 2
- If no response is seen after 1-2 weeks, the dose can be increased to 30 mg, though this may reduce the appetite-stimulating effect in some patients 4
- Mirtazapine has a relatively long half-life (20-40 hours), allowing for once-daily dosing, preferably at bedtime to minimize daytime sedation 3
Special Considerations
- Mirtazapine should not be routinely used for appetite stimulation in persons with dementia according to clinical practice guidelines, unless there is a concurrent depression that requires treatment 5
- In hospitalized patients, mirtazapine has shown numerical improvements in meal intake, though no significant difference compared to other appetite stimulants like dronabinol or megestrol acetate 6
- For patients with persistent anorexia without depression, megestrol acetate (starting at 160-200 mg daily) may be a more evidence-based first-line option than mirtazapine 7, 8
Potential Side Effects
- Common side effects at the 15 mg dose include sedation (most pronounced), dry mouth, increased appetite, and weight gain 1, 4
- Sedation tends to be more prominent at lower doses (15 mg) and may actually decrease at higher doses (30-45 mg) 4
- Unlike many other antidepressants, mirtazapine has minimal cardiovascular effects, anticholinergic effects, and lacks serotonergic side effects such as sexual dysfunction 3
Monitoring
- Monitor for weight gain, appetite improvement, and sedation within the first 1-2 weeks of treatment 2
- Be aware of rare but serious side effects such as agranulocytosis and neutropenia, which require monitoring of complete blood counts if symptoms of infection develop 1, 4
- Adjust dosing in patients with hepatic or renal impairment, as mirtazapine is extensively metabolized in the liver and excreted primarily in the urine 4