What are the appetite enhancers for individuals with loss of appetite?

Appetite Enhancers for Loss of Appetite

First-Line Pharmacological Agents

For patients with anorexia and advanced disease, megestrol acetate 400-800 mg daily is the primary appetite stimulant, though clinicians must weigh the significant risk of thromboembolic events (1 in 6 patients) and mortality (1 in 23 patients) against modest benefits (1 in 4 will have increased appetite, 1 in 12 will gain weight). 1, 2

Megestrol Acetate (Progestins)

• Dosing: Start with 400-800 mg daily, as this range demonstrates optimal appetite improvement and weight gain 2
• Efficacy: Increases appetite and body weight but does NOT increase fat-free mass (lean body mass) 1
• Critical safety concerns:
  • 1 in 6 patients develop thromboembolic phenomena (deep vein thrombosis, pulmonary embolism) 1, 2
  • 1 in 23 patients will die 1
  • Additional risks include impotence, vaginal spotting, and edema 1
  • In elderly patients undergoing resistance training, megestrol acetate may worsen functional performance rather than improve it 2
• Best suited for: Patients with months-to-weeks or weeks-to-days life expectancy where increased appetite is an important quality of life aspect 1

Corticosteroids (Dexamethasone)

• Dosing: 2-8 mg daily 2
• Duration: Restrict use to 1-3 weeks only 1
• Efficacy: Faster onset of action than megestrol acetate 2
• Critical limitations: The antianorectic effect is transient and disappears after a few weeks 1
• Side effects: Muscle wasting, insulin resistance (early metabolic effect), infections, myopathy, immunosuppression, and osteopenia (long-term) 1
• Best suited for: Patients with very short life expectancy (1-3 weeks) who have other symptoms that may be alleviated by corticosteroids such as pain or nausea 1

Second-Line Options

Mirtazapine

• Dosing: 7.5-30 mg at bedtime 2
• Efficacy: FDA labeling reports appetite increase in 17% of patients compared to 2% for placebo, with weight gain ≥7% of body weight in 7.5% of patients 3
• Best indication: Optimal choice when depression coexists with appetite loss, providing dual benefit 2
• Side effects: Somnolence (54% vs 18% placebo), which led to discontinuation in 10.4% of patients 3
• Cannot be recommended: For weight loss without depression in dementia patients due to insufficient evidence 2
• Inpatient data: Limited evidence shows numerical improvement in meal intake (mean change 17.12%) but no significant difference compared to other appetite stimulants 4

Agents NOT Recommended

Cannabinoids (Dronabinol, Cannabis)

• Insufficient evidence: Randomized trials in cancer patients with anorexia-cachexia syndrome did NOT demonstrate benefit over placebo for appetite or quality of life 1
• Comparative data: Megestrol acetate superior to dronabinol for promoting weight gain (75% vs 49%) and appetite (11% vs 3%) 1
• Significant adverse events: Euphoria, hallucinations, vertigo, psychosis, cardiovascular disorders, and high dropout rates 1, 2
• Limited potential use: May improve chemosensory perception and pre-meal appetite in patients with taste alterations, but evidence remains inconsistent 1

Olanzapine

• Mentioned as an option in NCCN guidelines but lacks detailed efficacy data in the provided evidence 1

Combination Therapy Approach

For cancer cachexia specifically, combination regimens yield superior outcomes compared to single agents. 1

• Optimal combination (Phase III trial, 332 patients): Medroxyprogesterone + megestrol acetate + eicosapentaenoic acid + L-carnitine + thalidomide showed superior outcomes versus single agents 1
• Alternative combination (Phase III trial, 104 patients with gynecologic cancers): Megestrol acetate + L-carnitine + celecoxib + antioxidants improved lean body mass, appetite, and quality of life compared to megestrol acetate alone 1

Nutritional Adjuncts

Omega-3 Fatty Acids (Fish Oil)

• Indication: Patients with advanced cancer undergoing chemotherapy at risk of weight loss or malnourished 1
• Efficacy: May stabilize or improve appetite, food intake, lean body mass, and body weight 1
• Evidence quality: Low, but recent reviews demonstrate beneficial effects on body composition during chemo/radiotherapy 1

Essential Pre-Treatment Steps

Before initiating appetite stimulants, address all reversible causes of anorexia: 1

• Oropharyngeal candidiasis
• Depression
• Pain
• Constipation
• Nausea/vomiting
• Early satiety (treat with metoclopramide) 1

Monitoring Requirements

• Weight: Regular monitoring essential, particularly with megestrol acetate 2
• Thromboembolic events: Active surveillance for deep vein thrombosis and pulmonary embolism with progestins 2
• Functional status: Especially in elderly patients on megestrol acetate undergoing physical therapy 2
• Regular reassessment: Essential to evaluate benefit versus harm, particularly in frail patients 2

Clinical Algorithm

1. First, address reversible causes (candidiasis, depression, pain, constipation, nausea) 1
2. For life expectancy of months-to-weeks: Consider megestrol acetate 400-800 mg daily if appetite is important for quality of life, with careful monitoring for thromboembolic events 1, 2
3. For life expectancy of 1-3 weeks: Consider dexamethasone 2-8 mg daily, especially if other symptoms (pain, nausea) need palliation 1, 2
4. If depression coexists: Mirtazapine 7.5-30 mg at bedtime is preferred 2
5. Avoid cannabinoids as routine therapy due to lack of efficacy and significant adverse effects 1, 2