What medications can stimulate appetite in patients with decreased appetite?

Appetite-Stimulating Medications

Megestrol acetate (400-800 mg/day) is the most effective first-line pharmacological appetite stimulant for patients with decreased appetite, demonstrating consistent improvements in appetite (approximately 25% of patients) and weight gain across multiple conditions including cancer, AIDS, and other chronic illnesses. 1, 2, 3

First-Line Pharmacological Options

Megestrol Acetate (Preferred)

• Start with 400-800 mg daily for most patients with anorexia-cachexia syndrome, as this dose range has demonstrated significant appetite improvement and weight gain in randomized controlled trials 1, 4, 3
• A lower dose of 160 mg twice daily (320 mg total) after meals is appropriate for initial therapy in advanced cancer patients, with considerable dose escalation possible if ineffective 5
• Meta-analysis of 35 trials (3,963 patients) showed consistent benefit versus placebo for appetite improvement and weight gain in cancer, AIDS, and other conditions 3
• Weight gain of ≥15 pounds occurred in 16% of patients receiving 800 mg daily versus 2% with placebo (P=0.003) 4
• Important caveat: Megestrol acetate increases risk of thromboembolic events, edema, and impotence; in one study, 800 mg daily attenuated beneficial effects of resistance training in hospitalized elderly patients 1

Corticosteroids (For Short-Term Use)

• Dexamethasone 2-8 mg/day offers faster onset of action and is most suitable for patients with shorter life expectancy (1-3 weeks) 1, 2, 6
• Corticosteroids provide transient appetite stimulation that disappears after a few weeks, with early onset of insulin resistance and later development of myopathy, immunosuppression, and osteopenia 1
• May be particularly useful when patients have concurrent symptoms (pain, nausea) that corticosteroids can address 1

Second-Line Options

Mirtazapine (For Concurrent Depression)

• Mirtazapine 7.5-30 mg at bedtime is the optimal choice when depression coexists with appetite loss, making it ideal for dual indication 2, 6
• In a retrospective study of 22 dementia patients, 30 mg daily resulted in mean weight gain of 1.9 kg at 3 months and 2.1 kg at 6 months, with 80% experiencing weight gain 1, 2
• Cannot be recommended for weight loss without depression in dementia patients due to insufficient evidence 1
• Lower starting doses (7.5-15 mg) should be used in elderly patients 6

Olanzapine

• Consider 5 mg/day specifically for patients with concurrent nausea and vomiting, as this addresses both symptoms simultaneously 2, 7
• Evidence for use in anorexia-cachexia is limited, but weight gain is a known side effect 7

Options NOT Recommended

Dronabinol (Cannabinoids)

• Dronabinol has insufficient and inconsistent evidence to support routine use for appetite stimulation 1
• In a randomized trial of 469 cancer cachexia patients, megestrol acetate (800 mg/day) demonstrated greater appetite and weight gain compared to dronabinol (2.5 mg twice daily) alone 1
• A multicenter RCT in 164 advanced cancer patients showed cannabis extract or THC (5 mg/day for 6 weeks) did not improve appetite or quality of life 1
• One small pilot study showed THC 2.5 mg twice daily for 18 days improved chemosensory perception and pre-meal appetite, but this has not been replicated 1
• Significant adverse events include euphoria, hallucinations, vertigo, psychosis, cardiovascular disorders, and high dropout rates 1, 8

Flavor Enhancers and Odor Stimulation

• Should NOT be routinely used in dementia patients, as studies showed no clinically relevant changes in appetite, nutritional intake, or body weight 1
• May be tried based on individual preferences but cannot be systematically recommended 1

Androgens

• Insufficient consistent clinical data to recommend currently approved androgenic steroids (nandrolone, oxandrolone, fluoxymesterone) for increasing muscle mass 1

Critical Safety Considerations

Megestrol Acetate Risks

• Monitor for thromboembolic events (deep vein thrombosis, pulmonary embolism) 1, 3
• Watch for vaginal spotting, impotence, and edema 1
• Deaths have been reported in association with megestrol acetate use 3
• In elderly patients undergoing resistance training, megestrol acetate may worsen functional performance rather than improve it 1

Corticosteroid Risks

• Limit use to 1-3 weeks maximum due to rapid development of adverse effects 1
• Early metabolic effects include insulin resistance; longer-term effects include myopathy, immunosuppression, and osteopenia 1

Non-Pharmacological Approaches to Implement Concurrently

• Provide emotional support during meals and ensure adequate feeding assistance, as social factors significantly impact intake 6, 7
• Serve energy-dense meals to meet nutritional requirements without increasing meal volume, allowing patients to consume adequate calories despite poor appetite 2, 7
• Offer oral nutritional supplements when food intake falls to 50-75% of usual intake 2
• Use protein-enriched foods and drinks to improve protein intake specifically 2
• Offer smaller, more frequent meals with favorite foods 6

Monitoring and Reassessment

• Regular reassessment is essential to evaluate benefit versus harm of all pharmacological interventions, particularly in frail patients 6, 7
• For patients approaching end of life, focus should shift to comfort and quality of life rather than nutritional goals 6
• Review all medications to identify potential contributors to poor appetite (iron supplements, multiple medications before meals) and consider temporarily discontinuing non-essential medications 6