Appetite Stimulants: Evidence-Based Recommendations
For patients with cancer-related appetite loss, clinicians may offer a short-term trial of megestrol acetate (400-800 mg/day) or corticosteroids (dexamethasone 2-8 mg/day), with the choice depending on life expectancy and side effect profile, though no FDA-approved medications exist specifically for cachexia and evidence remains insufficient to strongly endorse any pharmacologic agent. 1
Clinical Context Determines Optimal Agent Selection
Cancer-Related Anorexia/Cachexia
Megestrol acetate is the first-line pharmacological option when appetite stimulation is pursued, improving appetite in approximately 25% of patients and producing modest weight gain in about 8% 1, 2. The minimum effective dose is 160 mg/day, with 400-800 mg/day considered optimal; doses exceeding 480 mg/day show no additional benefit 3. However, megestrol acetate increases risks of thromboembolic events (RR 1.84), edema (RR 1.36), and death (RR 1.42) 1.
Corticosteroids (dexamethasone 2-8 mg/day) are appropriate alternatives, particularly for patients with short life expectancy (1-3 weeks), as their appetite-stimulating effect is transient and disappears after a few weeks 1. Corticosteroids may simultaneously address other symptoms like pain or nausea 1. Critical adverse effects include hyperglycemia, muscle wasting, immunosuppression (early manifestations), and osteopenia (long-term) 1, 4.
Depression with Concurrent Appetite Loss
Mirtazapine (7.5-30 mg at bedtime) is the optimal choice when depression coexists with appetite loss, addressing both conditions simultaneously 2. In patients with dementia and depression, mirtazapine 30 mg daily produced mean weight gain of 1.9 kg at three months and 2.1 kg at six months, with 80% experiencing weight gain 2. Avoid bupropion, as it is the only antidepressant consistently shown to promote weight loss 2.
AIDS-Related Anorexia
Dronabinol 2.5 mg twice daily (one hour before lunch and dinner) is FDA-approved for AIDS-related anorexia with weight loss 5. In a randomized, double-blind, placebo-controlled study of 139 patients, dronabinol showed statistically significant improvement in appetite at weeks 4 and 6, with trends toward improved body weight and mood 5. If side effects occur (feeling high, dizziness, confusion, somnolence—seen in 18% of patients), reduce to 2.5 mg once daily at supper or bedtime 5.
Chemotherapy-Induced Nausea with Appetite Loss
Olanzapine 5 mg/day may be considered for patients with concurrent nausea/vomiting 4. Dronabinol is also FDA-approved for chemotherapy-induced nausea/vomiting in patients who have failed conventional antiemetics, dosed 1-3 hours before chemotherapy and every 2-4 hours after for up to 4-6 doses daily 5.
Critical Contraindications and Populations to Avoid
Appetite stimulants should NOT be used in persons with dementia due to limited evidence, weak study methodology, inconsistent effects, and potential risks 2, 4, 3. Focus instead on non-pharmacological approaches including feeding assistance, emotional support during meals, and specific behavioral strategies 4.
Do not routinely offer enteral tube feeding or parenteral nutrition to manage cachexia in patients with advanced cancer outside clinical trials 1. A short-term trial of parenteral nutrition may be offered only to highly select patients with reversible bowel obstruction, short bowel syndrome, or malabsorption issues who are otherwise reasonably fit 1.
Monitoring Requirements and Duration
Corticosteroids should be limited to 1-3 weeks due to transient efficacy and cumulative toxicity 1. Monitor for thromboembolic events with megestrol acetate and assess for hyperglycemia, muscle wasting, and immunosuppression with dexamethasone 2, 4. Regular reassessment is essential to evaluate benefit versus harm, particularly in frail or elderly patients 2, 3.
For elderly patients, use lower starting doses with close monitoring for sedation and thromboembolic events 2. Early morning administration of dronabinol is associated with increased adverse events; dose later in the day 5.
Concurrent Non-Pharmacological Strategies
Refer patients to a registered dietitian for assessment and counseling on high-protein, high-calorie, nutrient-dense foods 1. Provide oral nutritional supplements when food intake is 50-75% of usual intake 1, 4. Serve energy-dense meals to meet nutritional requirements without increasing meal volume 1, 4. Offer protein-enriched foods and drinks to improve protein intake 1, 4.
Make snacks available between meals and provide emotional support during meals 2, 4. Place patients at dining tables rather than isolated in rooms to promote social interaction 4.
Evidence Quality and Limitations
No FDA-approved medications exist specifically for cancer cachexia, and evidence remains insufficient to strongly endorse any pharmacologic agent to improve cachexia outcomes 1. Clinicians may choose not to offer medications for cachexia treatment 1. The impact of appetite stimulants on overall quality of life is minimal despite improvements in appetite and modest weight gain 1. In hospitalized patients, appetite stimulants show limited efficacy on improving appetite and meal intake, with no significant weight change 6.