What are the treatment options for loss of appetite?

Treatment Options for Loss of Appetite

First-line treatment for loss of appetite requires identifying and treating reversible causes (oropharyngeal candidiasis, depression, pain, constipation, nausea), followed by consideration of appetite stimulants—specifically megestrol acetate, dexamethasone, or olanzapine—only when increased appetite meaningfully impacts quality of life in patients with limited life expectancy. 1

Algorithmic Approach to Treatment

Step 1: Address Reversible Causes First

• Treat underlying symptoms that interfere with food intake: pain, constipation, nausea/vomiting 1
• Evaluate for oropharyngeal candidiasis and treat if present 1
• Screen for and treat depression 1
• Use metoclopramide specifically for early satiety 1

Step 2: Pharmacologic Appetite Stimulants (For Patients with Months-to-Weeks Life Expectancy)

Megestrol Acetate (First-Line Pharmacologic Option)

• Improves appetite in 1 of 4 patients and weight in 1 of 12 patients 1
• Critical safety warning: 1 in 6 patients develop thromboembolic phenomena and 1 in 23 will die 1
• Higher doses show greater weight improvement than lower doses 1
• Modest weight gain when it occurs 1

Corticosteroids (Dexamethasone)

• Consider for short-term use only (1-3 weeks) in patients with advanced disease 1
• Antianorectic effect is transient and disappears after a few weeks 1
• Early adverse effects include myopathy, immunosuppression, and insulin resistance; long-term effects include osteopenia 1
• More suitable for patients with very short life expectancy, especially if other symptoms (pain, nausea) need palliation 1

Olanzapine

• Recommended as an appetite stimulant option 1
• Can also be used for persistent nausea 1

Step 3: Combination Therapy (For Select Patients)

Combination regimens show superior outcomes compared to single agents: 1

• Medroxyprogesterone + megestrol acetate + eicosapentaenoic acid + L-carnitine + thalidomide demonstrated superior outcomes in phase III trial of 332 patients 1
• Megestrol acetate + L-carnitine + celecoxib + antioxidants improved lean body mass, appetite, and quality of life in 104 patients with advanced gynecologic cancers 1

Step 4: Adjunctive Nutritional Interventions

Omega-3 Fatty Acids (Fish Oil)

• Consider supplementation with long-chain N-3 fatty acids in patients with advanced cancer undergoing chemotherapy who are at risk of weight loss 1
• May stabilize or improve appetite, food intake, lean body mass, and body weight 1

What NOT to Use

Cannabinoids (Limited Evidence)

• Cannabis extract and delta-9-tetrahydrocannabinol did NOT demonstrate benefit over placebo for appetite or quality of life in cancer-related anorexia-cachexia 1
• Dronabinol is inferior to megestrol acetate: only 49% vs 75% weight gain and 3% vs 11% appetite improvement 1
• May help some individual patients, but evidence is very limited 1

Parenteral Nutrition

• Generally NOT recommended except in highly select cases (e.g., non-functioning alimentary tract with relatively indolent malignancy causing multifocal bowel obstructions) 1
• Should be time-limited with prospectively agreed-upon goals and stopped if no benefit or when death is imminent 1
• Overly aggressive enteral or parenteral nutrition can actually increase suffering in dying patients 1

Critical Pitfalls to Avoid

• Do not use appetite stimulants in patients with years of life expectancy—focus on treating underlying causes and nutritional rehabilitation 1
• Do not ignore the serious thromboembolic risk with megestrol acetate (1 in 6 patients) 1
• Do not use corticosteroids long-term—muscle wasting and metabolic complications emerge within weeks 1
• Do not assume weight gain equals improved outcomes—megestrol acetate increases weight but not fat-free mass 1
• Avoid cannabinoids as first-line therapy—evidence does not support their use over proven alternatives 1

Special Considerations by Life Expectancy

Years to Months

• Focus on treating reversible causes 1
• Consider appetite stimulants if appetite is important for quality of life 1
• Nutrition support consultation appropriate 1

Months to Weeks

• Appetite stimulants (megestrol acetate, dexamethasone, olanzapine) are reasonable 1
• Short-term corticosteroids acceptable 1

Weeks to Days

• Shift focus from prolonging life to maintaining quality of life 1
• Treat dry mouth and thirst 1
• Provide family education about discontinuing feeding 1
• Avoid aggressive nutritional interventions 1

Physical Activity Component

• Recommend individualized resistance exercise plus aerobic exercise to maintain muscle strength and mass 1
• Moderate-intensity training (50-75% baseline maximum heart rate), three sessions weekly, 10-60 minutes per session 1
• Even daily walking reduces risks of atrophy from inactivity 1