What are the alternative appetite stimulants for a patient with leukemia who has not responded to mirtazapine (Remeron)?

Alternative Appetite Stimulants for Leukemia Patients Who Have Not Responded to Mirtazapine

For leukemia patients who have not responded to mirtazapine for appetite stimulation, megestrol acetate (400-800 mg/day) is the recommended first-line alternative, followed by olanzapine (5 mg/day) or dexamethasone (2-8 mg/day) as second-line options. 1

First-Line Alternative: Megestrol Acetate

• Megestrol acetate at doses of 400-800 mg/day is recommended as the primary alternative for cancer patients with anorexia who have failed mirtazapine therapy 1
• Approximately 1 in 4 patients treated with megestrol acetate will experience increased appetite, and 1 in 12 will have measurable weight gain 1
• Important safety considerations: 1 in 6 patients may develop thromboembolic phenomena, and there is a mortality risk (1 in 23 patients) 1
• Higher doses (>320 mg/day) have not shown additional benefit and may actually be associated with weight loss rather than gain 2

Second-Line Alternatives

Olanzapine

• Recommended at 5 mg/day for cancer-related anorexia 1
• May be particularly beneficial in patients who also have nausea or anxiety 1
• Has been shown to be effective in randomized trials for cancer-related anorexia 1

Dexamethasone

• Can be used at doses of 2-8 mg/day for short-term appetite stimulation 1
• Most appropriate for patients with limited life expectancy (months to weeks) due to side effect profile with prolonged use 1
• Provides rapid onset of appetite stimulation but benefits may diminish over time 1

Third-Line Option: Cannabinoids

• Cannabinoids (dronabinol) may be considered if other options fail 1
• Standard dosing is 2.5-7.5 mg orally every 4 hours as needed 1
• Evidence shows limited efficacy compared to megestrol acetate:
  • In direct comparison, megestrol acetate was superior for promoting weight gain (75% vs 49% of patients) and appetite improvement (11% vs 3%) 1
  • May still benefit some patients, particularly those with chemosensory alterations 1
• Caution: May induce delirium in elderly patients and is subject to local regulations 1

Combination Approaches

• For refractory cases, combination therapy may yield better outcomes than monotherapy 1
• Evidence supports combinations such as:
  • Megestrol acetate plus L-carnitine, celecoxib, and antioxidants 1
  • Megestrol acetate with dronabinol (though this showed only modest additional benefit over megestrol alone) 1

Monitoring and Supportive Care

• Address reversible causes of anorexia (oropharyngeal candidiasis, depression, pain, constipation, nausea) 1
• Consider metoclopramide for early satiety 1
• Nutrition consultation for calorie-dense, high-protein supplementation may provide additional benefit 1
• Monitor for adverse effects specific to each medication:
  • Megestrol acetate: thromboembolic events, edema, adrenal suppression 1
  • Olanzapine: sedation, metabolic effects 1
  • Dexamethasone: hyperglycemia, mood changes, insomnia, increased infection risk 1
  • Dronabinol: dizziness, confusion, drowsiness 1

Recent Evidence

• A 2024 randomized clinical trial in non-small cell lung cancer patients showed that while mirtazapine did not improve subjective appetite scores compared to placebo, it significantly increased energy intake (379.3 kcal increase) after 4 weeks, particularly fat intake, and reduced sarcopenia 3
• This suggests that for some patients, continuing mirtazapine at an increased dose or for a longer duration might be worth considering before switching to alternatives 3