First-Line Appetite Stimulant
Megestrol acetate 400-800 mg daily is the first-line appetite stimulant for patients with decreased appetite due to cancer, HIV/AIDS, or other chronic illnesses. 1, 2
Recommended Starting Approach
Start with megestrol acetate 400-800 mg orally once daily, with the liquid formulation preferred over tablets due to better bioavailability and lower cost. 1, 2, 3
- The American College of Nutrition specifically recommends 400-800 mg daily as the optimal dose range, with 800 mg/day showing superior efficacy in clinical trials. 1, 3
- A reasonable alternative is to start at 160-400 mg daily and titrate up to 480-800 mg based on response, though doses above 480 mg show diminishing additional benefit. 3
- One in four patients will experience appetite improvement, and one in twelve will gain weight. 2, 3
Critical Safety Warnings
Monitor closely for thromboembolic events, as these occur in approximately 1 in 6 patients (RR 1.84). 2, 3
- Deep vein thrombosis and pulmonary embolism are the most concerning complications. 3
- Mortality risk is increased (RR 1.42), with 1 in 23 patients dying from treatment-related complications. 3
- Edema occurs with RR 1.36. 3
- Weight gain is primarily adipose tissue rather than lean muscle mass, which may limit clinical benefit. 3
Alternative First-Line Option for Short Life Expectancy
For patients with life expectancy of 1-3 weeks, use dexamethasone 2-8 mg/day instead of megestrol acetate. 1, 3
- Dexamethasone offers faster onset of action, similar appetite stimulation, different toxicity profile, and significantly lower cost. 3
- Restrict corticosteroid use to maximum 1-3 weeks due to side effects including muscle wasting, insulin resistance, and increased infection risk. 3
Second-Line Options
Mirtazapine 7.5-30 mg at bedtime is the optimal second-line choice when depression coexists with appetite loss. 1, 2
- This provides dual benefit for both conditions simultaneously. 1
- Cannot be recommended for appetite stimulation alone without depression. 1, 2
Options NOT Recommended
Do not use dronabinol (cannabinoids) as first-line therapy due to insufficient and inconsistent evidence. 4, 1, 2
- Dronabinol is inferior to megestrol acetate, with only 49% of patients gaining weight compared to 75% with megestrol acetate. 2
- Significant adverse events include euphoria, hallucinations, vertigo, psychosis, and cardiovascular disorders. 1
- In elderly patients, cannabinoids may induce delirium. 2
Do not use appetite stimulants in persons with dementia due to limited evidence and potential harmful side effects. 2
Special Population Considerations
In elderly hospitalized patients undergoing resistance training, megestrol acetate 800 mg daily may worsen functional performance rather than improve it, causing smaller gains or deterioration in muscle strength. 2
- Consider combining megestrol acetate with resistance exercise programs in appropriate patients to preserve lean body mass. 3
Combination Therapy Options
Consider adding olanzapine 5 mg/day to megestrol acetate for enhanced weight gain, with one trial showing 85% vs 41% weight gain when combined. 3
- Multi-agent regimens including megestrol acetate plus L-carnitine, celecoxib, and antioxidants have shown improved outcomes in phase III trials. 2, 3
Duration and Monitoring
Limit duration of megestrol acetate therapy and reassess regularly, particularly after 12 weeks. 3
- Regular assessment for thromboembolic phenomena is essential. 3
- Monitor weight changes to assess response. 3
- Assess adrenal function in patients on long-term therapy. 3
Concurrent Non-Pharmacological Approaches
Implement emotional support during meals and ensure adequate feeding assistance, as social factors significantly impact intake. 1
- Serve energy-dense meals to meet nutritional requirements without increasing meal volume. 1