What are the best medication options for increasing appetite?

Best Medication Options for Increasing Appetite

Progestins, particularly megestrol acetate, are the most effective first-line medications for increasing appetite, with a recommended starting dose of 160-200 mg daily. 1, 2

First-Line Options

Progestins (Megestrol Acetate)

• Most extensively studied appetite stimulant with high-level evidence supporting its efficacy 2
• Recommended starting dose is 160-200 mg daily, which is considered the optimal initial dose 1
• Dose can be increased up to 480-800 mg daily if needed, though higher doses increase risk of side effects 2
• Increases appetite and body weight but primarily through fat gain, not lean muscle mass 2
• Demonstrated significant advantages over placebo for appetite improvement, increased caloric intake, and weight gain in multiple randomized controlled trials 2

Monitoring and Side Effects of Progestins

• Serious side effects include thromboembolic events (approximately one in six patients may develop these) 1
• Other potential adverse effects include edema, impotence, and vaginal spotting 2
• Regular monitoring for weight gain, appetite improvement, and adverse effects is essential 1
• Time-limited use (typically weeks to months) is recommended due to side effect profile 2

Second-Line Options

Cannabinoids (Dronabinol)

• FDA-approved for appetite stimulation in AIDS-related anorexia 3
• Initial dosage typically 2.5 mg twice daily 3
• Limited and inconsistent evidence for effectiveness in cancer-related anorexia 2
• In a small pilot study, THC (2.5 mg twice daily) improved chemosensory perception and pre-meal appetite compared to placebo 2
• Side effects include euphoria, hallucinations, vertigo, psychosis, and cardiovascular disorders 2
• Not recommended as first-line therapy due to inconsistent results and significant side effect profile 2

Mirtazapine

• Antidepressant with appetite-stimulating properties 4
• Increases appetite in 17% of patients compared to 2% for placebo 4
• Can lead to weight gain of ≥7% of body weight in 7.5% of patients 4
• May be particularly useful when depression co-exists with appetite loss 5
• Side effects include somnolence (54% of patients), which may limit daytime use 4

Emerging Options

Ghrelin Analogs

• Anamorelin (ghrelin receptor agonist) has shown promise in clinical trials 2
• Improved appetite, body weight, and lean body mass compared to placebo in patients with advanced non-small cell lung cancer 2
• Not yet approved for clinical use 2

Special Considerations

Inpatient Setting

• Limited evidence for effectiveness of appetite stimulants in hospitalized patients 6
• A small retrospective study showed numerical improvements in meal intake (average 17.12% increase) with dronabinol, megestrol acetate, or mirtazapine in hospitalized patients 5
• No significant differences between these three medications in the inpatient setting 5

Corticosteroids

• May be considered for very short-term use (1-3 weeks) in patients with advanced disease 2
• Side effects include muscle wasting, insulin resistance, and increased risk of infections 2
• Not recommended for long-term appetite stimulation due to significant adverse effects 2

Clinical Decision Algorithm

1. First-line therapy: Megestrol acetate starting at 160-200 mg daily 1

   • Monitor for appetite improvement and weight gain
   • If inadequate response after 2-4 weeks, consider dose increase up to 480-800 mg daily 2
   • Monitor closely for thromboembolic events and other side effects

2. If contraindicated or ineffective:

   • Consider dronabinol 2.5 mg twice daily if no contraindications 3
   • OR mirtazapine, particularly if depression is present 4, 5

3. For very short-term use only (1-3 weeks in advanced disease):

   • Consider corticosteroids with close monitoring for adverse effects 2

4. For all options:

   • Regularly assess effectiveness through appetite scores and weight measurements
   • Monitor for medication-specific adverse effects
   • Consider discontinuation if significant side effects occur or if no benefit after adequate trial