What medications can help increase appetite?

Medications to Increase Appetite

For most patients requiring appetite stimulation, megestrol acetate 400-800 mg daily is the first-line pharmacological option, with approximately 1 in 4 patients experiencing improved appetite and 1 in 12 achieving modest weight gain. 1, 2

First-Line Pharmacological Options

Megestrol Acetate (Primary Recommendation)

• Start with 400-800 mg daily as the most effective first-line agent for appetite stimulation 1, 2
• The minimum effective dose is 160 mg/day, with optimal dosing between 160-480 mg/day; doses above 480 mg/day show no additional benefit 2
• Expected outcomes: approximately 25% of patients will experience improved appetite and 8% will achieve modest weight gain 3, 1, 2
• Critical safety concerns require careful patient selection: 1 in 6 patients will develop thromboembolic events, 1 in 23 will die, and fluid retention is common 3, 2
• Additional adverse effects include edema, impotence, vaginal spotting, and adrenal suppression 4
• May attenuate benefits of resistance training, causing smaller gains or deterioration in muscle strength and functional performance 4

Dexamethasone (Alternative for Rapid Effect)

• Use 2-8 mg daily when faster onset of action is needed, particularly in patients with shorter life expectancy 1, 2
• Provides rapid appetite stimulation but carries significant risks with prolonged use including hyperglycemia, muscle wasting, insulin resistance, infections, and immunosuppression 1, 2
• Best reserved for palliative care settings where short-term benefit outweighs long-term risks 3

Mirtazapine (For Concurrent Depression)

• Prescribe 7.5-30 mg at bedtime for patients with concurrent depression and appetite loss 1, 4
• Start elderly patients at 7.5 mg at bedtime, with maximum dose of 30 mg at bedtime 4
• Addresses both depression and appetite simultaneously with beneficial side effects including promotion of sleep, appetite, and weight gain 4
• Expected outcomes: mean weight gain of 1.9 kg at 3 months and 2.1 kg at 6 months, with approximately 80% experiencing some weight gain 2, 4
• Requires at least 4-8 weeks for full therapeutic trial 4
• Common adverse effects include somnolence (54%), increased appetite (17%), weight gain (12%), and dizziness (7%) 5
• Discontinue over 10-14 days to limit withdrawal symptoms 4

Olanzapine (For Concurrent Nausea)

• Consider 5 mg daily for patients with concurrent nausea and vomiting 1
• Particularly useful when appetite loss is accompanied by chemotherapy-induced nausea 3

Context-Specific Considerations

Cancer-Related Anorexia/Cachexia

• Megestrol acetate remains the gold standard for cancer-related anorexia 3, 2
• Combination therapy may yield superior outcomes: medroxyprogesterone + megestrol acetate + eicosapentaenoic acid + L-carnitine + thalidomide showed better results than single agents 3
• Another effective combination: megestrol acetate + L-carnitine + celecoxib + antioxidants improved lean body mass, appetite, and quality of life 3
• Address reversible causes first: oropharyngeal candidiasis, depression, pain, constipation, nausea/vomiting 3
• Use metoclopramide for early satiety 3

Elderly Patients

• Start with lower doses and monitor closely for sedation and thromboembolic events 1, 2
• Regular reassessment is essential to evaluate benefit versus harm 1, 2, 4
• After 9 months of treatment, consider dosage reduction to reassess need for continued medication 4

Patients with Dementia

• Do NOT use appetite stimulants in patients with dementia who do not have concurrent depression 1, 2, 4
• Evidence shows no consistent benefit and potentially harmful side effects outweigh uncertain benefits for appetite and body weight (89% consensus agreement) 4
• Focus exclusively on non-pharmacological approaches for this population 1

Medications with Limited or No Evidence

Cannabinoids (Dronabinol)

• Limited evidence compared to megestrol acetate; reserve for select patients who have failed first-line options 3, 2
• Dose: 2.5-7.5 mg every 4 hours as needed 2
• May benefit patients with chemosensory alterations 2
• Critical warning: can induce delirium in elderly patients 3, 2
• Randomized trials show megestrol acetate superior to dronabinol for promoting weight gain (75% vs 49%) and appetite (11% vs 3%) 3
• Cannabis extract and delta-9-tetrahydrocannabinol did not demonstrate benefit over placebo for appetite and quality of life in cancer patients 3
• Three small placebo-controlled trials in dementia patients found no significant effect on body weight, BMI, or energy intake 4
• Side effects include feeling high, dizziness, confusion, and somnolence 6

Cyproheptadine

• May have modest benefit but adverse effects limit its use 2
• Not recommended as a first-line option 3, 2

Medications to Avoid

• Bupropion is contraindicated as it consistently promotes weight loss 2
• Hydrazine sulphate is not an appetite stimulant 2

Non-Pharmacological Approaches (Use First or Concurrently)

Nutritional Interventions

• Provide oral nutritional supplements (ONS) when food intake is 50-75% of usual intake 1, 2
• Offer protein-enriched foods and drinks to improve protein intake 1
• Serve energy-dense meals to meet nutritional requirements without increasing meal volume 1
• Make snacks available between meals 1
• Provide texture-modified, enriched foods for patients with chewing or swallowing difficulties 1

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 mealtimes 1
• Ensure consistent caregivers during meals when possible 1
• Increase time spent by nursing staff on feeding assistance 1
• Create a relaxed, comfortable, and safe environment during meals 1
• Offer foods according to individual preferences 1
• Provide finger foods for patients with difficulty using utensils 1

Medication Review

• Identify and discontinue medications that may contribute to poor appetite (e.g., iron supplements, multiple medications taken before meals) 4

Clinical Algorithm for Decision-Making

1. Assess for reversible causes: depression, pain, nausea, constipation, medication side effects 3, 4
2. Implement non-pharmacological interventions first: nutritional support, environmental modifications, behavioral strategies 1, 2
3. Select pharmacological agent based on clinical context:
   • Cancer-related anorexia: Megestrol acetate 400-800 mg daily 3, 1, 2
   • Concurrent depression: Mirtazapine 7.5-30 mg at bedtime 1, 4
   • Concurrent nausea: Olanzapine 5 mg daily 1
   • Short life expectancy: Dexamethasone 2-8 mg daily 1, 2
   • Dementia without depression: NO pharmacological intervention 1, 2, 4
4. Monitor closely: Reassess benefit versus harm regularly, especially for thromboembolic events with megestrol acetate 1, 2, 4
5. Consider combination therapy if single agents fail 3

Important Caveats

• Appetite stimulants should be used in combination with or after failure of dietetic and oral nutritional management 2
• Evidence for appetite stimulants in the inpatient setting is limited, with studies showing numerical improvements in meal intake but no significant difference between agents 7, 8
• For end-of-life patients, focus on comfort and quality of life rather than aggressive nutritional interventions 4
• The benefit-to-harm ratio must be carefully considered, particularly given the serious adverse effects of megestrol acetate (thromboembolic events, mortality risk) 3, 2