How can appetite be stimulated in patients with decreased appetite?

Appetite Stimulation in Patients with Decreased Appetite

Megestrol acetate 400-800 mg/day is the first-line pharmacological appetite stimulant for most patients with decreased appetite, demonstrating significant improvement in appetite (approximately 25% of patients) and modest weight gain (approximately 8% of patients). 1

First-Line Pharmacological Options

Megestrol Acetate (Preferred Agent)

• The minimum effective dose is 160 mg/day, with 400-800 mg/day being the optimal range for appetite stimulation and weight gain in cancer patients and other conditions 2, 1
• Doses above 480 mg/day show no additional efficacy 2
• Results in statistically significant appetite improvement (68% vs 48% placebo, P=0.003) and weight gain ≥15 lbs in 16% of patients versus 2% with placebo (P=0.003) 3
• Critical safety concerns include thromboembolic events (higher death rates versus placebo in some studies), edema, impotence, vaginal spotting, and adrenal suppression 4, 5
• May attenuate benefits of resistance training, causing smaller gains or deterioration in muscle strength 4

Corticosteroids (Alternative for Shorter Life Expectancy)

• Dexamethasone 2-8 mg/day provides faster onset of action compared to megestrol acetate, making it suitable for patients with limited life expectancy 1, 4
• Corticosteroids are established appetite stimulants (level of evidence B1), though optimal dosing and scheduling remain undefined 2
• Significant side effects with prolonged use include hyperglycemia, muscle wasting, and immunosuppression 1

Mirtazapine (For Concurrent Depression)

• Mirtazapine 7.5-30 mg at bedtime is the preferred agent when depression coexists with appetite loss 1, 4
• Start with 7.5 mg at bedtime in elderly patients, with maximum dose of 30 mg 4
• Mean weight gain of 1.9 kg at 3 months and 2.1 kg at 6 months, with approximately 80% experiencing some weight gain 4
• Requires 4-8 weeks for full therapeutic trial 4
• Sedating properties make bedtime dosing ideal 4

Olanzapine (For Concurrent Nausea/Vomiting)

• Olanzapine 5 mg/day may be considered specifically for patients with concurrent nausea and vomiting 1

Context-Specific Recommendations

Cancer Patients

• Both megestrol acetate and corticosteroids are recommended for cancer-related anorexia/cachexia 6
• Progestins increase appetite and body weight but not fat-free mass 4
• Megestrol acetate also reduces nausea (13% vs 38% placebo, P=0.001) and emesis (8% vs 25%, P=0.009) 3

Elderly Patients

• Start with lower doses and monitor closely for sedation and thromboembolic events 1
• For elderly with depression: mirtazapine 7.5-15 mg at bedtime is first-line 4
• For elderly without depression: megestrol acetate 400-800 mg/day, with approximately 1 in 4 patients experiencing increased appetite and 1 in 12 gaining weight 4

Patients with Dementia

• Appetite stimulants are NOT recommended for persons with dementia due to limited evidence and potential risks (89% consensus agreement) 1, 4
• Focus exclusively on non-pharmacological approaches for this population 1

Hospitalized Patients

• Dronabinol, megestrol, and mirtazapine show numerical improvements in meal intake (mean change 17.12%) when initiated in the inpatient setting 7
• Almost half (48%) of hospitalized patients experience documented improvement in diet after starting appetite stimulants 7
• No serious adverse effects observed in the inpatient setting 7

Non-Pharmacological Approaches (Should Precede or Accompany Pharmacotherapy)

Environmental and Social Interventions

• Place patients at dining tables rather than isolated in rooms to promote social interaction 1
• Provide emotional support, supervision, verbal prompting, and encouragement during mealtimes 1
• Ensure consistent caregivers during meals when possible 1
• Increase time spent by nursing staff on feeding assistance 1

Nutritional Strategies

• Provide oral nutritional supplements (ONS) when food intake falls to 50-75% of usual intake 1, 4
• Serve energy-dense meals to meet nutritional requirements without increasing meal volume 1
• Offer protein-enriched foods and drinks to improve protein intake 1
• Make snacks available between meals and at other times if requested 1
• Provide texture-modified, enriched foods for patients with chewing or swallowing difficulties 1
• Offer finger foods for patients who have difficulty using utensils 1

Medication Review

• Identify and consider temporarily discontinuing non-essential medications that may contribute to poor appetite (e.g., iron supplements, multiple medications taken before meals) 4

Agents NOT Recommended

Cannabinoids/Dronabinol

• Limited and inconsistent evidence does not support routine use 2, 4
• FDA-approved for AIDS-related anorexia at 5 mg/day (2.5 mg before lunch and dinner), with statistically significant appetite improvement at weeks 4 and 6 8
• High dropout rate due to adverse events (18% required dose reduction to 2.5 mg/day due to feeling high, dizziness, confusion, somnolence) 2, 8
• Three small placebo-controlled trials in dementia patients found no significant effect on body weight, BMI, or energy intake 4
• May improve chemosensory perception and pre-meal appetite in select cancer patients 2

Other Agents

• Cyproheptadine may be an appetite stimulant but has reported adverse effects (level of evidence C) 2, 6
• Metoclopramide, nandrolone, pentoxifylline, and hydrazine sulfate have not shown appetite-stimulating effects and should only be used in clinical trials 2

Implementation Algorithm

1. Assess clinical context: Identify underlying condition (cancer, AIDS, dementia, depression), life expectancy, and concurrent symptoms
2. Implement non-pharmacological strategies first: Environmental modifications, nutritional support, medication review 1
3. Select pharmacological agent based on patient characteristics:
   • Depression present → Mirtazapine 7.5-30 mg at bedtime 1, 4
   • Nausea/vomiting present → Olanzapine 5 mg/day 1
   • Shorter life expectancy → Dexamethasone 2-8 mg/day 1
   • Dementia without depression → No pharmacological agent 1, 4
   • All other patients → Megestrol acetate 400-800 mg/day 1, 6
4. Monitor closely: Regular reassessment for benefit versus harm, particularly for thromboembolic events, edema, and other adverse effects 1, 4
5. Reassess after 4-8 weeks: If ineffective, consider alternative agent or discontinuation 4

Critical Pitfalls to Avoid

• Do not use appetite stimulants systematically in dementia patients without depression due to lack of benefit and potential harm 1, 4
• Do not exceed megestrol acetate 480 mg/day as higher doses provide no additional benefit 2
• Do not overlook thromboembolic risk with megestrol acetate, particularly in immobile or high-risk patients 4, 5
• Do not use dexamethasone long-term without considering significant metabolic and immunosuppressive effects 1
• Do not prescribe mirtazapine without allowing 4-8 weeks for full therapeutic effect 4
• Do not discontinue mirtazapine abruptly; taper over 10-14 days to limit withdrawal symptoms 4