What is the recommended treatment for stimulating appetite?

Recommended Treatment for Stimulating Appetite

Megestrol acetate 160-200 mg daily is the recommended first-line medication for appetite stimulation, with the strongest evidence for efficacy in increasing appetite and body weight. 1

First-Line Treatment: Megestrol Acetate

• Start with megestrol acetate 160-200 mg daily as the optimal initial dose, which represents the minimum effective dose with robust evidence from multiple randomized controlled trials 1, 2

• One in four patients will experience increased appetite, and one in twelve will achieve weight gain with this regimen 1

• The dose can be escalated up to 480-800 mg daily if the initial dose is insufficient, though doses above 480 mg/day show no clear additional efficacy and increase side effect risk 1, 2

Important Caveats with Megestrol Acetate

• Thromboembolic events occur in approximately 1 in 6 patients, with mortality risk of 1 in 23 patients, requiring careful patient selection and monitoring 1

• Weight gain occurs primarily through fat accumulation rather than lean muscle mass, which is an important consideration for functional outcomes 1

• In older hospitalized patients with functional decline, megestrol acetate (800 mg daily) may actually impair muscle strength and functional performance, potentially attenuating benefits of resistance training 1

Second-Line Treatment: Dronabinol

• Dronabinol should be reserved as a second-line option when megestrol acetate is contraindicated or ineffective, as it has limited and inconsistent evidence compared to first-line therapy 1, 3

• Start with 2.5 mg twice daily (one hour before lunch and dinner), avoiding early morning dosing which increases adverse effects 4

• If side effects occur (feeling high, dizziness, confusion, somnolence—affecting 18% of patients), reduce to 2.5 mg once daily at supper or bedtime 4

• Dronabinol is significantly less effective than megestrol acetate: only 49% achieve weight gain versus 75% with megestrol, and only 3% show appetite improvement versus 11% with megestrol 1, 3

Specific Warnings for Dronabinol

• Cannabinoid administration in elderly patients may induce delirium, requiring extreme caution in this population 1, 3

• Side effects include euphoria, hallucinations, vertigo, psychosis, dizziness, somnolence, cognitive impairment, and dysphoria 1, 3

Alternative Options Based on Clinical Context

Mirtazapine

• Consider mirtazapine ONLY when depression coexists with weight loss, as it serves dual purposes in that specific context 1, 2

• Mirtazapine is NOT recommended solely for appetite stimulation or weight loss without concurrent depression 1, 2

Corticosteroids

• Reserve corticosteroids for very short-term use (1-3 weeks) in patients with advanced disease and limited life expectancy 1, 2

• Avoid long-term use due to significant adverse effects including muscle wasting, insulin resistance, and increased infection risk 1

Populations Where Appetite Stimulants Should NOT Be Used

• Appetite stimulant drugs should NOT be used in persons with dementia due to limited evidence, inconsistent effects, and potential harmful side effects 1, 2

• Exercise caution in older hospitalized patients undergoing rehabilitation, as megestrol may worsen functional outcomes 1

Combination Therapy for Refractory Cases

• For cancer-related anorexia not responding to single agents, consider combination therapy with megestrol acetate plus L-carnitine, celecoxib, and antioxidants 1

• Another effective combination includes medroxyprogesterone, megestrol acetate, eicosapentaenoic acid, L-carnitine supplementation, and thalidomide 1

Practical Implementation Algorithm

1. Assess for contraindications: Check for thromboembolic risk factors, dementia, or active rehabilitation needs 1

2. First choice: Initiate megestrol acetate 160-200 mg daily with close monitoring for thromboembolic events 1, 2

3. If megestrol contraindicated or ineffective: Switch to dronabinol 2.5 mg twice daily, with particular caution in elderly patients 3, 4

4. If depression coexists: Consider mirtazapine as it addresses both conditions 1, 2

5. For advanced disease with short life expectancy: Corticosteroids may be appropriate for 1-3 weeks only 1, 2

6. Integrate nutritional consultation alongside pharmacological interventions, as calorie-dense, high-protein supplementation shows efficacy for weight stabilization 1