Medications to Boost Appetite

Megestrol acetate is the most effective first-line medication for increasing appetite, with a recommended starting dose of 160-200 mg daily. 1

First-Line Option: Megestrol Acetate

Megestrol acetate is the most extensively studied and effective appetite stimulant with high-level evidence supporting its efficacy for cancer-related anorexia and other conditions 1, 2
The recommended starting dose is 160-200 mg daily, which is considered the optimal initial dose 1, 2
The dose can be increased up to 480-800 mg daily if needed, though higher doses increase the risk of side effects 1
One in four patients treated with megestrol acetate will experience increased appetite, and one in twelve will have weight gain 3
For patients who may benefit from a lower dose, 80 mg twice daily after meals has been shown to be an effective starting dose 4

Megestrol acetate increases appetite and body weight primarily through fat gain rather than lean muscle mass 1
It has demonstrated significant advantages over placebo for appetite improvement, increased caloric intake, and weight gain in multiple randomized controlled trials 1, 5
In addition to appetite stimulation, megestrol acetate may also have anti-inflammatory effects 6

Important side effects to monitor include:
- Thromboembolic phenomena (occurs in approximately 1 in 6 patients) 3, 2
- Edema 2
- Impotence and vaginal spotting 2
- Mortality risk (1 in 23 patients) 3
Patients should be monitored for weight gain, appetite improvement, and potential adverse effects throughout treatment 2

Cannabinoids, such as dronabinol, have limited and inconsistent evidence for effectiveness in cancer-related anorexia 1
Dronabinol is FDA-approved for treatment of anorexia associated with weight loss in patients with AIDS 7
The initial dosage of dronabinol is typically 5 mg/day, administered as 2.5 mg one hour before lunch and dinner 7
Due to side effects, dosage may need to be reduced to 2.5 mg/day as a single dose at supper or bedtime 7
Dronabinol may improve pre-meal appetite compared to placebo, but is less effective than megestrol acetate for promoting weight gain (49% vs 75% of patients) and appetite improvement (3% vs 11%) 3

Common side effects include feeling high, dizziness, confusion, and somnolence (occurring in approximately 18% of patients) 7
More serious side effects can include euphoria, hallucinations, vertigo, psychosis, and cardiovascular disorders 1
Patients should be advised not to operate motor vehicles or dangerous machinery while taking dronabinol 7
Cannabinoid administration in elderly patients may induce delirium 3

For very short-term use (1-3 weeks) in patients with advanced disease, corticosteroids may be considered, but are not recommended for long-term appetite stimulation due to significant adverse effects 1
Combination therapy approaches may yield better outcomes for patients with cancer cachexia:
- A combination of medroxyprogesterone, megestrol acetate, eicosapentaenoic acid, L-carnitine supplementation, and thalidomide has shown superior outcomes compared to single agents 3
- Another effective combination includes megestrol acetate plus L-carnitine, celecoxib, and antioxidants 3
Nutritional consultation should be considered alongside pharmacological interventions, as calorie-dense, high-protein supplementation has shown some efficacy for weight stabilization 3
Emerging options include ghrelin analogs such as anamorelin, which have shown promise in improving appetite, body weight, and lean body mass in clinical trials 1

Start with megestrol acetate at 160-200 mg daily for most patients 1, 2
Consider lower doses (80 mg twice daily) in patients who may be sensitive to side effects 4
Monitor for thromboembolic events, especially at higher doses 3, 2
Consider dronabinol as a second-line option, particularly in AIDS patients 7
Be aware that cannabinoid use is subject to local state rules and regulations 3
For children with cancer-related anorexia, megestrol acetate has been shown to be effective with few side effects 8