Does mirtazapine stimulate appetite?

Mirtazapine's Effect on Appetite Stimulation

Yes, mirtazapine does stimulate appetite, which is a well-documented side effect of the medication that can be beneficial in certain clinical scenarios but should not be used solely for appetite stimulation without depression.

Mechanism and Evidence for Appetite Stimulation

Mirtazapine has a strong appetite-stimulating effect that is recognized in multiple clinical guidelines and the FDA drug label:

• The FDA drug label specifically lists "increased appetite" as a common side effect, occurring in 17% of patients taking mirtazapine compared to only 2% for placebo 1.
• This appetite stimulation leads to weight gain in approximately 12% of patients taking mirtazapine, compared to 2% for placebo 1.
• The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines acknowledge that mirtazapine causes weight gain as a side effect 2.

Clinical Evidence of Weight Gain

The appetite-stimulating effect of mirtazapine translates to measurable weight gain:

• In a retrospective study of patients with Alzheimer's disease, 77.3% of patients gained weight after 3 months of mirtazapine therapy (mean gain of 1.93 kg or 3.9% of initial body weight) and 82.3% gained weight after 6 months (2.11 kg or 4.6%) 3.
• The FDA label reports that in U.S. clinical studies, weight gain of ≥7% of body weight was reported in 7.5% of patients treated with mirtazapine, compared to 0% for placebo 1.
• In pediatric trials, 49% of mirtazapine-treated patients had weight gain of at least 7%, compared to only 5.7% of placebo-treated patients 1.

Appropriate Clinical Use

Despite its appetite-stimulating properties, guidelines recommend specific contexts for mirtazapine use:

• For patients with depression and poor appetite: Mirtazapine can be beneficial when both conditions are present, as it addresses both issues simultaneously 4.
• In palliative care settings: Mirtazapine may be useful for anorexia when patients also have sleep difficulties or mood disorders 4.
• For specific conditions with weight loss: Case reports suggest mirtazapine may help with weight loss associated with conditions like gastroparesis 5.

Important Cautions

Guidelines specifically warn against using mirtazapine solely for appetite stimulation:

• The ESPEN guideline explicitly states: "Drugs to stimulate appetite or weight gain should NOT be used in persons with dementia" 2.
• The use of mirtazapine solely for appetite stimulation is not recommended due to potential risks that outweigh uncertain benefits 4.
• Significant side effects include somnolence (54% vs 18% for placebo), which resulted in discontinuation for 10.4% of patients 1.
• Other potential risks include QTc prolongation, discontinuation syndrome, and rarely but seriously, agranulocytosis 1.

Monitoring Recommendations

If mirtazapine is used in appropriate clinical scenarios where both depression and poor appetite are present:

• Monitor for excessive weight gain, as this is a common side effect 4, 1.
• Watch for sedation, which is the most common adverse effect (54% of patients) 1.
• Be aware of potential QTc prolongation, especially in patients with cardiovascular disease or taking other QTc-prolonging medications 1.
• Monitor for rare but serious side effects like agranulocytosis or neutropenia 1.

In conclusion, while mirtazapine definitively stimulates appetite, clinical guidelines recommend against using it solely for this purpose due to its side effect profile. It should be reserved for patients who have both depression and poor appetite, where its dual effect can be beneficial.