What medications are used for appetite stimulation?

Appetite Stimulation Medications

Megestrol acetate is the first-line medication for appetite stimulation, starting at 160-200 mg daily, with the strongest evidence for improving appetite and weight gain across multiple patient populations. 1, 2

First-Line Recommendation: Megestrol Acetate

Megestrol acetate should be initiated at 160-200 mg daily as the optimal starting dose, which represents the minimum effective dose with proven efficacy. 1, 2 This progestin has the most extensive evidence base among appetite stimulants, demonstrating consistent benefits in randomized controlled trials. 1

Dosing Strategy

• Start with 160-200 mg daily (the minimum effective and optimal initial dose). 1, 2
• Escalate up to 480-800 mg daily if inadequate response, though higher doses significantly increase thromboembolic risk. 1
• Administer after meals to optimize absorption and tolerability. 3
• Evaluate response after 4 weeks before considering dose escalation or alternative agents. 4

Expected Outcomes

• One in four patients will experience increased appetite. 1
• One in twelve patients will achieve weight gain, primarily through fat accumulation rather than lean muscle mass. 1
• Weight gain of 15 pounds or more occurs in approximately 16% of patients compared to 2% with placebo. 5

Critical Safety Considerations

• Thromboembolic events occur in approximately one in six patients (17%), representing the most significant risk. 1, 2
• Mortality risk is one in 23 patients treated with megestrol acetate. 1
• Other adverse effects include edema, impotence, vaginal spotting, and potential cortisol suppression. 2, 4
• In older hospitalized patients with functional decline, megestrol acetate (800 mg daily) may attenuate benefits of resistance training, causing smaller gains or deterioration in muscle strength and functional performance. 6

Second-Line Option: Dronabinol

Dronabinol is less effective than megestrol acetate and should be reserved for patients who cannot tolerate or fail first-line therapy. 1

Dosing and Administration

• Start with 2.5 mg twice daily (one hour before lunch and one hour before dinner), avoiding early morning dosing which increases adverse effects. 7
• If side effects occur (18% of patients), reduce to 2.5 mg once daily at supper or bedtime. 7
• Maximum dose is 5 mg twice daily for appetite stimulation. 7

Comparative Efficacy

• Only 49% of dronabinol patients experience weight gain versus 75% with megestrol acetate. 1
• Only 3% report appetite improvement versus 11% with megestrol acetate. 1
• Dronabinol may improve chemosensory perception and pre-meal appetite compared to placebo. 1

Safety Profile

• Side effects include euphoria, hallucinations, vertigo, psychosis, and cardiovascular disorders. 1
• In elderly patients, cannabinoids may induce delirium. 1
• Use is subject to local state regulations. 1

Third-Line Option: Cyproheptadine (Pediatric Patients)

For pediatric oncology patients, cyproheptadine is the preferred initial agent, with megestrol acetate reserved as second-line therapy due to higher risks in children. 4

• Administer orally as tablets or crushed via nasogastric tube if needed. 4
• Evaluate response after 4 weeks before switching to megestrol acetate. 4

Medications NOT Recommended

Mirtazapine

Mirtazapine should NOT be used solely for appetite stimulation or weight loss. 6 While one small study showed mean weight gain of 1.9 kg at three months and 2.1 kg at six months in dementia patients, this was uncontrolled and retrospective. 6 Mirtazapine may be considered only when depression coexists with weight loss, as it can serve dual purposes in that specific context. 6

Corticosteroids

Corticosteroids should only be considered for very short-term use (1-3 weeks) in patients with advanced disease, not for long-term appetite stimulation. 1 They cause significant adverse effects including muscle wasting, insulin resistance, and increased infection risk. 1

Specific Contraindication: Dementia Patients

Appetite stimulant drugs should NOT be used in persons with dementia. 6 Evidence is extremely limited, with cannabinoids, antidepressants, megestrol acetate, and neuroleptics tested only in small studies without consistent effects. 6 The uncertain benefits do not outweigh potential harmful side effects in this population. 6

Advanced Combination Therapy

For refractory cases in cancer-related anorexia, combination therapy may be superior to single agents:

• Medroxyprogesterone + megestrol acetate + eicosapentaenoic acid + L-carnitine + thalidomide. 1
• Megestrol acetate + L-carnitine + celecoxib + antioxidants. 1

Monitoring Parameters

• Assess appetite improvement, weight gain, and adverse effects at 4-week intervals. 2, 4
• Monitor specifically for thromboembolic events (leg swelling, chest pain, shortness of breath) given the 17% incidence. 1, 2
• Consider nutritional consultation alongside pharmacotherapy, as calorie-dense, high-protein supplementation shows efficacy for weight stabilization. 1