What is the best approach to managing appetite loss in patients with depression, specifically regarding the use of appetite stimulants?

Managing Appetite Loss in Patients with Depression: Pharmacological Approaches

Mirtazapine is the most appropriate first-line appetite stimulant for patients with depression experiencing appetite loss, as it effectively treats both depression and stimulates appetite. 1, 2

First-Line Approach: Mirtazapine

• Mirtazapine (7.5-30 mg at bedtime) is effective for patients with concurrent depression and appetite loss, making it an ideal choice for this specific population 1
• In a small retrospective study of patients with dementia, mirtazapine at 30 mg daily resulted in a mean weight gain of 1.9 kg after three months and 2.1 kg after six months, with about 80% of patients experiencing weight gain 3
• Mirtazapine is known to increase appetite as a side effect, with appetite increase reported in 17% of patients compared to 2% for placebo in controlled clinical studies 4
• Weight gain of ≥7% of body weight was reported in 7.5% of patients treated with mirtazapine, compared to 0% for placebo 4

Alternative Options When Mirtazapine Is Not Suitable

For Patients with Depression:

• Bupropion is the only antidepressant consistently shown to promote weight loss, making it unsuitable for patients with appetite loss 3, 5
• Within the SSRI class, fluoxetine and sertraline have been associated with weight loss with short-term use and weight neutrality with long-term use 3
• Paroxetine (SSRI) and amitriptyline (tricyclic) are associated with greater risk for weight gain compared to other antidepressants in their respective classes 3, 6

For Patients with Severe Appetite Loss:

• Megestrol acetate (400-800 mg/day) is recommended as an effective pharmacological appetite stimulant, with improvement in appetite in approximately 25% of patients 1, 2
• Dexamethasone (2-8 mg/day) offers a faster onset of action, making it suitable for patients with shorter life expectancy 1, 2
• Olanzapine (5 mg/day) may be considered for patients with concurrent nausea/vomiting 1

Monitoring and Safety Considerations

• Monitor for somnolence, which was reported in 54% of patients treated with mirtazapine compared to 18% for placebo 4
• Avoid concomitant use of benzodiazepines and alcohol with mirtazapine 4
• Screen patients for any personal or family history of bipolar disorder before initiating mirtazapine, as it may precipitate a mixed/manic episode 4
• Be aware of potential QTc prolongation with mirtazapine, particularly in patients with cardiovascular disease or taking other QTc-prolonging medications 4

Non-Pharmacological Approaches

• Provide emotional support during meals and ensure adequate feeding assistance 2
• Serve energy-dense meals to help patients meet nutritional requirements without increasing meal volume 1
• Offer oral nutritional supplements when food intake is between 50-75% of usual intake 1
• Protein-enriched foods and drinks can improve protein intake in patients with poor appetite 1

Treatment Algorithm

1. First step: Assess severity of depression and appetite loss
2. For patients with depression and appetite loss: Start mirtazapine 7.5-15 mg at bedtime, titrating up to 30 mg as needed 1, 4
3. If mirtazapine is contraindicated or not tolerated:
   • Consider paroxetine or amitriptyline if appropriate for the type of depression 3, 6
   • For severe appetite loss, add megestrol acetate 1, 2
4. For patients with shorter life expectancy: Consider dexamethasone for faster onset of action 1, 2
5. Regularly reassess benefit versus harm of pharmacological interventions 2

Important Caveats

• In a small inpatient study comparing dronabinol, megestrol, and mirtazapine, there was no significant difference between groups in meal intake change, but all showed numerical improvement in percentage meal intake (mean change 17.12%) 7
• Loss of appetite in melancholic depression follows a specific pattern, with decreased desire to eat, hunger, and prospective food consumption, along with increased satiety and diminished pleasure from eating 8
• Compounds that antagonize or downregulate serotonin receptors (like mirtazapine) are more likely to stimulate carbohydrate hunger and weight gain 6
• Lower starting doses should be used for elderly patients with close monitoring for side effects 2