What are the treatment options for appetite stimulants in patients with loss of appetite?

Appetite Stimulant Treatment Options

For patients with loss of appetite, megestrol acetate (400-800 mg/day) is the first-line pharmacological appetite stimulant, improving appetite in approximately 25% of patients and producing modest weight gain in about 8% of patients. 1

First-Line Pharmacological Options

Megestrol Acetate

• Megestrol acetate is the most effective first-line agent at doses of 400-800 mg/day, with the minimum effective dose being 160 mg/day and no additional benefit above 480 mg/day 1, 2
• Produces significant improvement in appetite (Level B1 evidence) and beneficial effects on body weight 2
• Critical warning: 1 in 6 patients will develop thromboembolic phenomena and 1 in 23 will die, making risk-benefit assessment essential 3
• Can cause fluid retention requiring monitoring 1

Dexamethasone

• Use 2-8 mg/day when faster onset of action is needed 1, 4
• Particularly suitable for patients with shorter life expectancy (weeks to months) 3, 1
• Significant side effects with prolonged use include hyperglycemia, muscle wasting, and immunosuppression 1
• Should not be used long-term due to adverse effect profile 1

Mirtazapine

• Ideal choice for patients with concurrent depression and appetite loss at 7.5-30 mg at bedtime 1, 4
• In patients with dementia, 30 mg daily produced mean weight gain of 1.9 kg at three months and 2.1 kg at six months, with approximately 80% experiencing weight gain 4
• Addresses both mood and appetite simultaneously 4

Olanzapine

• Consider 5 mg/day for patients with concurrent nausea and vomiting 1, 4
• Dual benefit for symptom management 1

Second-Line and Alternative Options

Cannabinoids (Dronabinol)

• Very limited evidence for cancer-related anorexia/cachexia, with randomized trials showing no benefit over placebo for appetite and quality of life 3
• May increase meal consumption in certain populations, but evidence is weak 1
• FDA-approved for AIDS-related anorexia, showing statistically significant improvement in appetite at weeks 4 and 6 in controlled trials 5
• Initial dosing: 2.5 mg one hour before lunch and dinner; reduce to 2.5 mg/day at supper or bedtime if side effects occur (feeling high, dizziness, confusion, somnolence) 5

Medroxyprogesterone Acetate

• Alternative progestational agent with Level B1 evidence for appetite stimulation 2
• Similar mechanism to megestrol acetate 2

Cyproheptadine

• May stimulate appetite but adverse effects have been reported (Level C evidence) 2
• Less preferred due to side effect profile 2

Combination Therapy Approach

For cancer-related cachexia, combination therapy yields superior outcomes compared to single agents: 3

• A phase III trial (332 patients) showed best results with: medroxyprogesterone + megestrol acetate + eicosapentaenoic acid + L-carnitine + thalidomide 3
• Another phase III trial (104 patients with gynecologic cancers) demonstrated improved lean body mass, appetite, and quality of life with: megestrol acetate + L-carnitine + celecoxib + antioxidants 3

Non-Pharmacological Interventions

Environmental and Behavioral Strategies

• Place patients at dining tables rather than isolated in rooms to promote social interaction 1
• Provide emotional support, supervision, verbal prompting, and encouragement during meals 1
• Ensure consistent caregivers during meals when possible 1
• Increase nursing staff time on feeding assistance 1
• Create relaxed, comfortable, and safe environment during meals 1

Nutritional Strategies

• Provide oral nutritional supplements (ONS) when food intake is 50-75% of usual intake 1
• Serve energy-dense meals to meet requirements without increasing volume 1, 4
• Offer protein-enriched foods and drinks to improve protein intake 1, 4
• Make snacks available between meals 1
• Provide finger foods for patients with difficulty using utensils 1
• Offer texture-modified, enriched foods for patients with swallowing difficulties 1

Address Reversible Causes

• Treat oropharyngeal candidiasis 3
• Manage depression 3
• Control symptoms interfering with food intake: pain, constipation, nausea/vomiting 3
• Use metoclopramide for early satiety 3

Special Population Considerations

Patients with Dementia

• Pharmacological appetite stimulants are NOT recommended due to limited evidence and potential risks 1, 2
• Focus exclusively on non-pharmacological approaches: feeding assistance, emotional support, behavioral strategies 1

Elderly Patients

• Use lower starting doses with close monitoring for side effects, particularly sedation and thromboembolic events 1, 4

Patients with Depression

• Mirtazapine is the preferred agent as it addresses both conditions 4
• Avoid bupropion as it consistently promotes weight loss 4
• Paroxetine and amitriptyline are associated with greater weight gain risk if appetite stimulation is desired 4

Critical Implementation Points

Monitoring Requirements

• Regular reassessment is essential to evaluate benefit versus harm 1, 4
• Monitor for thromboembolic events with megestrol acetate 3, 1
• Watch for hyperglycemia, muscle wasting, and immunosuppression with dexamethasone 1
• Assess sedation risk in elderly patients 1

Realistic Expectations

• Inpatient studies show no significant difference between dronabinol, megestrol, or mirtazapine for change in meal intake or weight, though numerical improvements in meal intake (mean 17.12%) may occur 6
• Almost half (48%) of hospitalized patients experience documented improvement in diet after starting medications 6
• Evidence for inpatient use is limited in quality and generalizability 7

Timing Considerations

• For patients with months-to-weeks or weeks-to-days life expectancy, only use appetite stimulants if increased appetite is an important aspect of quality of life 3
• Avoid overly aggressive nutritional interventions in dying patients as they can increase suffering 3