What medications increase appetite?

Medications That Increase Appetite

Megestrol acetate is the most effective medication for increasing appetite, with high-quality evidence showing significant appetite stimulation and weight gain, though it carries risks of thromboembolism and fluid retention that must be monitored. 1

First-Line Options

Progestins

• Megestrol acetate:
  • Dosage: 160-800 mg/day
  • Mechanism: Progestin that stimulates appetite through unclear mechanisms
  • Benefits: Significantly increases appetite and body weight compared to placebo 1, 2
  • Considerations: Weight gained is primarily fat mass rather than lean body mass 1
  • Risks: Thromboembolism (84% increased risk), fluid retention, and potential increased mortality 3

Corticosteroids

• Dexamethasone:
  • Recommended for short-term use only (1-3 weeks)
  • Provides rapid appetite stimulation
  • Limitations: Side effects include muscle wasting, insulin resistance, and increased infection risk 1, 3

Second-Line Options

Antihistamines

• Cyproheptadine:
  • Dosage: 2-4 mg three times daily
  • Well-established safety profile
  • Effective in various populations, though less effective in progressive diseases like cancer and HIV 4, 5
  • Side effects: Primarily mild sedation

Antidepressants

• Mirtazapine:
  • Dosage: 15-30 mg daily
  • Dual benefit: Treats both anxiety and appetite symptoms
  • FDA label notes increased appetite in 17% of patients (vs 2% for placebo) 6
  • Weight gain of ≥7% body weight reported in 7.5% of patients 6
  • Side effects: Somnolence (54%), dry mouth (25%), constipation (13%) 6

Other Options

Cannabinoids

• Limited evidence for weight impact despite improving perceived appetite 1
• Insufficient consistent data to recommend for anorexia in cancer patients 1

Olanzapine

• Alternative with fewer thromboembolic risks (5 mg/day)
• Requires monitoring for metabolic side effects 3

Comparative Effectiveness

• In direct comparisons, megestrol acetate showed superior weight gain compared to other drugs (mean difference 2.5 kg) 7
• A small study comparing megestrol acetate and cyproheptadine found similar energy intake increases (approximately 500 kcal) and moderate weight gain with both treatments, though megestrol was associated with impotence in some patients 4
• In hospitalized patients, no significant difference was found between dronabinol, megestrol, and mirtazapine for meal intake improvement, though all showed numerical improvements 8

Selection Algorithm

1. For short-term rapid appetite stimulation (1-3 weeks):

   • Dexamethasone (if no contraindications)

2. For longer-term appetite stimulation:

   • First choice: Megestrol acetate (if no history of thromboembolism)
   • Alternative if anxiety/depression present: Mirtazapine
   • Alternative if concerned about thromboembolism: Cyproheptadine or mirtazapine

3. For elderly patients:

   • Consider starting with cyproheptadine due to better safety profile
   • Mirtazapine if sleep disturbance or depression is also present

Monitoring Recommendations

• Weight: Regular monitoring to assess effectiveness
• Thromboembolism signs (with megestrol): Leg pain/swelling, chest pain, shortness of breath
• Fluid retention: Monitor for edema, especially with megestrol
• Sedation: Particularly with mirtazapine and cyproheptadine
• Metabolic parameters: Blood glucose with corticosteroids, lipid profile with longer-term use

Important Caveats

• Weight gained with megestrol acetate is primarily fat mass rather than lean body mass
• Corticosteroids should be limited to short-term use due to significant side effects
• Consider combining pharmacological approaches with nutritional counseling and physical activity when possible
• Most studies were conducted in specific populations (cancer, HIV), so effects may vary in other conditions
• Risk-benefit assessment is essential, particularly in elderly patients who may be more susceptible to side effects