What medications can be used to stimulate appetite?

Appetite Stimulants: Evidence-Based Recommendations

Megestrol acetate (400-800 mg/day) is the most effective first-line pharmacological appetite stimulant, with demonstrated improvement in appetite in approximately 25% of patients and modest weight gain in about 8% of patients. 1

First-Line Pharmacological Options

Megestrol Acetate (Preferred)

• Start with 160 mg/day as the minimum effective dose, which appears to be optimal for most patients 2
• Doses up to 800 mg/day can be used, though evidence does not support greater efficacy beyond 480 mg/day 2
• Results in significant appetite increase and beneficial effect on body weight (Level of Evidence: B1) 2
• Weight gain occurs primarily through increased body fat rather than lean muscle mass 3
• Important caveat: Can cause fluid retention and increased risk of thromboembolic events 1

Corticosteroids (Alternative First-Line)

• Dexamethasone 2-8 mg/day offers faster onset of action compared to megestrol acetate 1, 4
• Best suited for patients with shorter life expectancy due to rapid effect 1, 4
• Established as appetite stimulants (Level of Evidence: B1) 2
• Major limitation: Significant side effects with prolonged use including hyperglycemia, muscle wasting, and immunosuppression 1
• Optimal dosing and scheduling remain undefined 2

Second-Line Options for Specific Clinical Scenarios

Mirtazapine (For Concurrent Depression)

• Dose: 7.5-30 mg at bedtime 1, 4
• Ideal choice when depression coexists with appetite loss 1, 4
• Small retrospective study showed mean weight gain of 1.9 kg at 3 months and 2.1 kg at 6 months with 30 mg daily, with 80% of patients experiencing weight gain 2
• Cannot be recommended for weight loss without depression 2

Olanzapine (For Concurrent Nausea/Vomiting)

• Dose: 5 mg/day 1, 4
• Consider specifically when nausea or vomiting accompanies poor appetite 1, 4

Dronabinol (Limited Evidence)

• FDA-approved for AIDS-related anorexia with demonstrated statistically significant improvement in appetite at weeks 4 and 6 compared to placebo 5
• Initial dose: 5 mg/day (2.5 mg before lunch and dinner), may reduce to 2.5 mg/day if side effects occur 5
• Side effects (feeling high, dizziness, confusion, somnolence) occurred in 18% of patients at 5 mg/day dose 5
• Limited evidence in general populations; should be reserved for specific cases 2

Medroxyprogesterone Acetate (MPA)

• Results in significant appetite increase (Level of Evidence: B1) but weight gain effect not confirmed (Level of Evidence: C) 2
• Minimum effective dose: 200 mg/day 2
• Less preferred than megestrol acetate due to inconsistent weight gain effects 2

Medications NOT Recommended

The following agents lack evidence of appetite-stimulating effects and should only be used in clinical trials: 2

• Dronabinol (except for AIDS-related anorexia where FDA-approved) 2
• Metoclopramide 2
• Nandrolone 2
• Pentoxifylline 2
• Hydrazine sulphate (definitively NOT an appetite stimulant, Level of Evidence: A) 2
• Cyproheptadine (may have some effect but adverse effects reported, Level of Evidence: C) 2

Special Population: Patients with Dementia

Pharmacological appetite stimulants are NOT recommended for patients with dementia due to limited evidence and potential risks 2, 1

• Evidence for dronabinol, antidepressants, megestrol acetate, and neuroleptics tested only in small studies with weak methodology 2
• Megestrol acetate showed mixed results in nursing home residents, with only 41% having dementia in available studies 2
• One study showed 800 mg/day megestrol acetate attenuated beneficial effects of resistance training, causing smaller gains or deterioration in muscle strength and functional performance 2

Clinical Implementation Algorithm

Step 1: Initial Assessment

• Identify underlying cause of poor appetite (cancer, AIDS, depression, dementia, other)
• Assess for concurrent symptoms (depression, nausea/vomiting)
• Evaluate life expectancy and treatment goals

Step 2: Non-Pharmacological Interventions First

• Appetite stimulants should be used in combination with or after failure of dietetic and oral nutritional management 2
• Provide oral nutritional supplements when intake is 50-75% of usual 1
• Offer protein-enriched and energy-dense foods 1

Step 3: Select Appropriate Pharmacological Agent

• Cancer patients with anorexia/cachexia: Megestrol acetate 160-800 mg/day OR dexamethasone 2-8 mg/day 2, 1
• AIDS-related anorexia: Dronabinol 2.5-5 mg/day OR megestrol acetate 400-800 mg/day 5, 3
• Depression with appetite loss: Mirtazapine 7.5-30 mg at bedtime 1, 4
• Nausea/vomiting with poor appetite: Olanzapine 5 mg/day 1, 4
• Dementia patients: Focus on non-pharmacological approaches only 2, 1

Step 4: Dosing Considerations

• Start elderly patients on lower doses with close monitoring for sedation and thromboembolic events 1, 4
• For megestrol acetate, begin with 160 mg/day and titrate up to 800 mg/day if needed, though doses above 480 mg/day show no additional benefit 2

Step 5: Monitoring

• Regular reassessment is essential to evaluate benefit versus harm 1, 4
• Monitor for specific adverse effects: fluid retention and thromboembolism with megestrol acetate; hyperglycemia, muscle wasting, and immunosuppression with corticosteroids 1
• Assess appetite improvement, weight changes, and quality of life at regular intervals 5

Key Clinical Pitfalls to Avoid

• Do not use megestrol acetate alone for muscle wasting—it increases primarily body fat, not lean muscle mass; combine with resistance training and consider anabolic agents when appropriate 3
• Avoid prolonged corticosteroid use due to cumulative adverse effects; reserve for patients with limited life expectancy 1
• Do not prescribe mirtazapine solely for appetite stimulation without concurrent depression, as evidence is limited to this specific population 2
• Never use pharmacological appetite stimulants as first-line in dementia patients—prioritize feeding assistance, emotional support during meals, and behavioral strategies instead 2, 1
• Avoid early morning dosing of dronabinol—associated with increased frequency of adverse experiences compared to later-day dosing 5