What are alternative appetite stimulants if a patient cannot tolerate off-label Mirtazepine (mirtazapine)?

Alternative Appetite Stimulants When Mirtazapine Cannot Be Tolerated

For patients who cannot tolerate mirtazapine as an appetite stimulant, megestrol acetate and dexamethasone are the most evidence-supported alternatives, though both carry significant risks that must be weighed against potential benefits. 1

First-Line Alternatives

Megestrol Acetate

• Recommended for patients with cancer-related anorexia/cachexia when increased appetite is important for quality of life 1
• Dosage typically ranges from 160-800 mg daily 1, 2
• Benefits:
  • Improves appetite in approximately 1 in 4 patients 1
  • Modest weight gain (primarily adipose tissue) in approximately 1 in 12 patients 1
• Risks:
  • Thromboembolic events (affects 1 in 6 patients) 1, 3
  • Edema 1
  • Adrenal suppression 1
  • Mortality risk (1 in 23 patients) 1

Dexamethasone

• Appropriate for patients with shorter life expectancy (weeks to months) 1
• Benefits:
  • Similar appetite improvement to megestrol acetate 1
  • May also help with fatigue 1
  • Faster onset of action compared to other options 1
• Limitations:
  • Efficacy tends to decline with long-term use 1
  • Side effects include fluid retention, hyperglycemia, muscle wasting, and immunosuppression 1

Second-Line Alternatives

Cannabinoids (Dronabinol)

• Limited evidence in dementia and cancer patients 1
• Small studies show:
  • Increased body weight and triceps skinfold thickness in Alzheimer's patients 1
  • Improved meal consumption in geriatric neuropsychiatric patients with dementia 1
• Considerations:
  • Mechanism of action not fully understood 1
  • Side effects include somnolence and cognitive effects 1
  • Less effective than megestrol acetate for weight gain in cancer patients 1

Olanzapine

• May be considered for patients with concurrent nausea/vomiting 1
• Limited evidence specifically for anorexia/cachexia but:
  • Known to cause weight gain as side effect when used for psychiatric conditions 1
  • One small study showed improved appetite scores in advanced cancer patients 1
• Side effects include sedation, metabolic changes, and risk of falls 1

Special Considerations

For Patients with Concurrent Depression

• If depression is present and mirtazapine cannot be tolerated, consider:
  • Other antidepressants with appetite-stimulating properties 1
  • Combined approach with antidepressant plus appetite stimulant 1

For Elderly Patients

• Lower starting doses of all medications 1
• Closer monitoring for side effects, particularly:
  • Sedation with cannabinoids or olanzapine 1
  • Thromboembolic events with megestrol acetate 1, 3

Non-Pharmacological Approaches

• Should be implemented alongside pharmacological interventions:
  • Provide emotional support during meals 1
  • Ensure adequate feeding assistance 1
  • Serve energy-dense meals 1
  • Consider texture modification for patients with dysphagia 1
  • Maintain regular oral care 1

Important Caveats

• Current guidelines do not recommend systematic use of appetite stimulants in dementia patients due to limited evidence and potential risks 1
• Benefits must be weighed against risks, particularly in frail patients 1
• Treatment goals should focus on quality of life rather than simply weight gain 1
• Regular reassessment is essential to evaluate benefit versus harm 1