What medications can be used to increase appetite in patients with decreased appetite?

Medications to Increase Appetite

For most patients with decreased appetite, megestrol acetate 400-800 mg daily is the first-line pharmacological option, demonstrating significant appetite improvement and weight gain in randomized controlled trials, though clinicians must carefully weigh this benefit against serious risks including thromboembolism, edema, and potential mortality. 1

First-Line Pharmacological Agent

Megestrol acetate remains the primary evidence-based appetite stimulant across multiple conditions:

• The optimal dose range is 400-800 mg daily, with higher doses showing greater weight improvement than lower doses 1, 2
• Patients can expect appetite improvement in approximately 25% of cases and weight gain in approximately 1 in 12 patients 3
• Mean weight gain of 2.25 kg has been demonstrated in meta-analyses comparing megestrol acetate to placebo 4
• Lower doses (160 mg twice daily after meals) may be appropriate as a starting dose, with considerable dose escalation possible if ineffective 5

Critical Safety Warnings for Megestrol Acetate

Serious adverse events occur more frequently with megestrol acetate and must be monitored:

• Thromboembolic events (deep vein thrombosis, pulmonary embolism) occur at higher rates 1, 2
• Edema, impotence, and vaginal spotting are common side effects 2
• One Cochrane review found higher rates of deaths in the megestrol acetate group compared to placebo 2
• In elderly patients undergoing resistance training, megestrol acetate may attenuate beneficial effects and worsen functional performance rather than improve it 1, 3
• Adrenal suppression can occur with prolonged use 3

Context-Specific Recommendations

For Patients with Concurrent Depression

Mirtazapine 7.5-30 mg at bedtime is the optimal choice when depression coexists with appetite loss:

• This addresses both conditions simultaneously, making it ideal for dual indication 1, 6
• Initial dosing should be 7.5 mg at bedtime for elderly patients, with maximum dose of 30 mg 3
• A full therapeutic trial requires at least 4-8 weeks to assess efficacy 3
• In one small retrospective study, 30 mg daily resulted in 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, 2
• Sedating properties make bedtime dosing ideal 3

For Patients with Dementia

Appetite stimulants should NOT be used in patients with dementia who do not have concurrent depression:

• Evidence shows no consistent benefit and potentially harmful side effects outweigh uncertain benefits for appetite and body weight 2
• This recommendation has 89% consensus agreement in clinical nutrition guidelines 2
• Mirtazapine may be considered only if depression is also present requiring treatment 2

For Patients with Short Life Expectancy

Dexamethasone 2-8 mg daily offers faster onset of action:

• Most suitable for patients with life expectancy of 1-3 weeks 1, 3
• Provides more rapid symptom relief than megestrol acetate 2
• Should be used for restricted periods (1-3 weeks) due to side effects including muscle wasting, insulin resistance, and infections 2

For Cancer Patients with Advanced Disease

Progestins can be considered but with significant caveats:

• The ESPEN guidelines suggest considering progestins to increase appetite in anorectic cancer patients with advanced disease 2
• More than 30 randomized clinical trials have studied progestins in over 4,000 cancer patients 2
• Progestins increase appetite and body weight but NOT fat-free mass 2
• The influence on quality of life is minimal or inconsistent 2

Medications NOT Recommended

Cannabinoids (Dronabinol)

There is insufficient consistent clinical data to recommend cannabinoids:

• Multiple guidelines conclude evidence is insufficient to support routine use for appetite stimulation 1, 2
• Significant adverse events include euphoria, hallucinations, vertigo, psychosis, cardiovascular disorders, and high dropout rates 1
• FDA labeling warns of neuropsychiatric adverse reactions, hemodynamic instability, seizures, and paradoxical nausea/vomiting 7
• Elderly patients, especially those with dementia, have increased risk of confusion, falls, and blood pressure changes 7
• Three small placebo-controlled trials in dementia patients found no significant effect on body weight, BMI, or energy intake 2

Non-Pharmacological Approaches to Implement Concurrently

These interventions should accompany any pharmacological treatment:

• Provide emotional support during meals and ensure adequate feeding assistance, as social factors significantly impact intake 1, 3
• Serve energy-dense meals to meet nutritional requirements without increasing meal volume 1, 6
• Offer oral nutritional supplements when food intake falls to 50-75% of usual intake 3, 6
• Protein-enriched foods and drinks can improve protein intake in patients with poor appetite 6
• Encourage shared meals with family or other patients to improve intake through social interventions 3

Monitoring and Reassessment

Regular evaluation is essential for all pharmacological interventions:

• Monitor for thromboembolic events with megestrol acetate use 1
• After 9 months of mirtazapine treatment, consider dosage reduction to reassess need for continued medication 3
• Discontinue mirtazapine over 10-14 days to limit withdrawal symptoms 3
• Reassess benefit versus harm regularly, particularly in frail patients 1, 3
• If approaching end of life, focus on comfort and quality of life rather than aggressive nutritional goals 3