What are the options for appetite stimulants in patients with decreased appetite?

Appetite Stimulant Options

Megestrol acetate is the first-line appetite stimulant, starting at 160-200 mg daily, with the option to increase to 480-800 mg daily if needed, though higher doses increase thromboembolic risk without clear additional benefit. 1

First-Line Pharmacological Option

Megestrol acetate is the most extensively studied and effective appetite stimulant with high-level evidence (B1) supporting its use. 2, 1

Dosing Strategy

• Start with 160-200 mg daily as the minimum effective and optimal initial dose 2, 1
• Can escalate to 400-800 mg daily if initial dose is ineffective 1, 3
• No evidence supports doses above 480 mg daily having superior efficacy 2
• Twice-daily dosing after meals (e.g., 80 mg twice daily) is an appropriate alternative starting regimen 3

Expected Outcomes

• 1 in 4 patients will experience increased appetite 1
• 1 in 12 patients will achieve weight gain 1
• Weight gain is primarily fat mass, not lean muscle mass 1
• Appetite improvement occurs in 95% of patients within 2 weeks 4

Critical Safety Concerns

• Thromboembolic events occur in approximately 1 in 6 patients 1
• Mortality risk is 1 in 23 patients 1
• Adrenal suppression is common: 33% at 200 mg, 70% at 400 mg, and 78% at 800 mg develop morning cortisol <8 ng/mL 5
• Other side effects include edema, impotence, and vaginal spotting 6
• In elderly hospitalized patients, megestrol acetate may attenuate benefits of resistance training, causing deterioration in muscle strength and functional performance 1, 6

Second-Line Options

Corticosteroids

• Effective appetite stimulants (level B1 evidence) but should be reserved for very short-term use only (1-3 weeks) 2, 1
• Not recommended for long-term appetite stimulation due to significant adverse effects including muscle wasting, insulin resistance, and increased infection risk 1
• Dexamethasone 2-8 mg daily may be considered for patients with shorter life expectancy and need for faster onset of action 6
• Insufficient information exists to define optimal dosing and scheduling 2

Dronabinol (Cannabinoid)

• Limited and inconsistent evidence for effectiveness in cancer-related anorexia 1
• Not recommended as first-line therapy due to inconsistent results and significant side effect profile 1
• May improve chemosensory perception and pre-meal appetite compared to placebo 1
• Side effects include euphoria, hallucinations, vertigo, psychosis, and cardiovascular disorders 1
• Less effective than megestrol acetate: 49% vs 75% for weight gain, 3% vs 11% for appetite improvement 1
• In FDA trials, initial dosing was 2.5 mg one hour before lunch and dinner (5 mg/day total), with dose reduction to 2.5 mg/day as single evening dose if side effects occurred 7
• May induce delirium in elderly patients 1

Medroxyprogesterone Acetate (MPA)

• Effective appetite stimulant with level B1 evidence 2, 8
• Results in significant increase in appetite 8
• Can be used as alternative to megestrol acetate 2

Context-Specific Recommendations

Patients with Concurrent Depression

• Mirtazapine 7.5-30 mg at bedtime is the preferred option when depression coexists with weight loss 1, 6
• Addresses both conditions simultaneously with beneficial side effects including promotion of sleep and appetite 6
• Initial dose should be 7.5 mg at bedtime in elderly patients, with maximum of 30 mg 6
• Full therapeutic trial requires 4-8 weeks to assess efficacy 6
• Mean weight gain of 1.9 kg at 3 months and 2.1 kg at 6 months, with approximately 80% experiencing some weight gain 6
• Not recommended solely for appetite stimulation without depression 1

Patients with Dementia

• Appetite stimulant drugs should NOT be used in persons with dementia due to limited evidence and potential harmful side effects 1, 6
• This recommendation has 89% consensus agreement among experts 6
• Exception: Mirtazapine may be considered only if concurrent depression is present 6

Cancer Patients

• Both megestrol acetate and corticosteroids are recommended for cancer-related anorexia/cachexia 2, 8
• Combination therapy may be superior: medroxyprogesterone + megestrol acetate + eicosapentaenoic acid + L-carnitine + thalidomide 1
• Alternative combination: megestrol acetate + L-carnitine + celecoxib + antioxidants 1

Elderly Patients

• Lower initial doses and more rigorous monitoring of side effects are recommended 8
• Consider megestrol acetate 400-800 mg daily if mirtazapine is ineffective or contraindicated 6
• Regular reassessment is essential to evaluate benefit versus harm 6
• After 9 months of treatment, consider dosage reduction to reassess need for continued medication 6

Emerging Options

Ghrelin Analogs (Anamorelin)

• Have shown promise in clinical trials, improving appetite, body weight, and lean body mass compared to placebo in patients with advanced non-small cell lung cancer 1
• Not yet widely available for routine clinical use 1

Treatment Algorithm

1. Optimize dietetic and oral nutritional management first 2
2. For patients without depression: Start megestrol acetate 160-200 mg daily 1
3. For patients with concurrent depression: Start mirtazapine 7.5 mg at bedtime 1, 6
4. For cancer patients with very short life expectancy: Consider dexamethasone 2-8 mg daily for rapid effect 6
5. If initial therapy fails: Escalate megestrol acetate to 400-800 mg daily or consider combination therapy 1
6. Avoid entirely: Appetite stimulants in dementia patients without depression 1, 6

Important Caveats

• Hydrazine sulphate is NOT an appetite stimulant (level A evidence) 2
• Appetite stimulants should be used in combination with or after failure of dietetic and oral nutritional management 2
• Cannabinoids have insufficient evidence to support routine use for appetite stimulation 6
• Three small placebo-controlled trials in dementia patients found no significant effect of cannabinoids on body weight, BMI, or energy intake 6
• Cyproheptadine may be an appetite stimulant but adverse effects have been reported (level C evidence) 8