Appetite Stimulants in Frail Older Adults: Weighing the Evidence
The phenomenon of unintentional weight loss is common in frail older adults and is a predictor of increased morbidity and mortality. However, a growing body of evidence and consensus guidelines from organizations like the American Geriatrics Society (AGS) strongly advise against using prescription appetite stimulants in this population. Most studies show no significant improvement in crucial patient-centered outcomes such as quality of life, functional status, or survival. In fact, some agents, like megestrol acetate, have been linked to increased mortality.
The Lack of Evidence for Meaningful Outcomes
Unlike in populations with cancer or AIDS-related cachexia, studies evaluating appetite stimulants in frail older adults have consistently failed to demonstrate benefits beyond minimal and often transient weight gain.
- Limited Weight Gain: While some studies show modest weight increases, this gain is often due to increased body fat rather than lean muscle mass, which is crucial for reversing frailty. For example, one trial found that older adults given megestrol acetate and an exercise program gained weight but experienced a deterioration in physical function.
- No Functional Improvement: Improving functional status, such as walking speed or strength, is a key goal in managing frailty. Appetite stimulants have not been shown to reliably improve these physical functions.
- Quality of Life: Several studies have found no correlation between the use of megestrol acetate and improved quality of life in frail patients.
Significant Risks and Side Effects
The medications commonly prescribed off-label as appetite stimulants carry serious risks that can be particularly dangerous for older adults, who are more susceptible to adverse effects.
- Megestrol Acetate (Megace): This synthetic progestin is FDA-approved only for AIDS-related anorexia. In older adults, its use is associated with a significantly increased risk of venous thromboembolism (blood clots), fluid retention, and potentially death. The AGS's Beers Criteria, which lists medications to be avoided in older adults, explicitly includes megestrol acetate.
- Mirtazapine (Remeron): While this antidepressant can increase appetite and cause weight gain as a side effect, there is little evidence to support its use for weight gain in the absence of depression. It can also cause side effects like significant sedation, dizziness, and constipation in older adults. The AGS advises against its use for targeted appetite stimulation in frail older adults without another indication.
- Cannabinoids (e.g., Dronabinol): Derived from cannabis, dronabinol is approved for anorexia in AIDS patients but not for frail older adults. Its use is associated with neurological side effects, including dizziness, thinking abnormalities, confusion, and somnolence, all of which increase the risk of falls.
- Cyproheptadine: This antihistamine is often avoided in older adults due to its anticholinergic properties, which can cause confusion, sedation, and other side effects.
A Better Approach: Prioritizing Nonpharmacologic Interventions
Given the significant risks and lack of proven benefit, expert guidelines recommend focusing on nonpharmacologic strategies to address the root causes of weight loss in frail older adults. A multidisciplinary team is essential for a comprehensive approach.
- Identify Underlying Causes: Many factors can contribute to unintended weight loss. A thorough evaluation should address potential issues such as:
- Dental problems (poorly fitting dentures)
- Underlying medical conditions (e.g., infections, endocrine disorders)
- Psychological issues (e.g., depression, dementia, social isolation)
- Medication side effects (polypharmacy is a common culprit)
- Swallowing difficulties (dysphagia)
- Optimize Nutrition and Hydration: Nutritional interventions are a cornerstone of care. These strategies include:
- Offering nutrient-dense foods and high-calorie supplements
- Providing smaller, more frequent meals to accommodate reduced appetite
- Enhancing the dining environment to make meals more enjoyable
- Ensuring adequate protein intake to help maintain muscle mass, with supplementation if needed
- Physical Activity: Exercise, particularly resistance training, is one of the most effective ways to combat frailty. Combining exercise with nutritional support has been shown to yield significant improvements in lean body mass, grip strength, and physical performance.
Comparison of Appetite Stimulants vs. Nonpharmacologic Approaches
| Feature | Appetite Stimulants (e.g., Megestrol, Dronabinol) | Nonpharmacologic Approaches (e.g., Nutritional Support, Exercise) |
|---|---|---|
| Effect on Frailty | No reliable improvement in core frailty outcomes like function and survival; minimal or mixed results on weight. | Demonstrates significant, measurable improvements in strength, physical performance, and overall frailty scores, especially when combined. |
| Key Outcome | Primarily associated with modest weight gain (often fat mass), not improved function. | Focuses on improving functional status, lean body mass, and quality of life by addressing root causes. |
| Risks/Side Effects | High potential for severe side effects, including blood clots, fluid retention, dizziness, confusion, and increased mortality (especially with megestrol). | Minimal to no side effects, with most strategies promoting overall health and well-being. |
| Underlying Cause | Does not address the root causes of appetite loss, such as depression, poor oral health, or medication side effects. | Directly investigates and treats the underlying causes, leading to more sustainable improvements. |
| Cost | Can be costly; potential for additional healthcare costs due to managing side effects. | Generally lower cost; may involve resources like dietitians but offers a more effective, long-term solution. |
Conclusion
The evidence overwhelmingly suggests that using prescription appetite stimulants to improve outcomes in frail older adults is not an effective or safe strategy. The potential for serious adverse effects, including increased mortality with some agents, outweighs the minimal and often non-functional weight gain they may provide. Current best practice, supported by major geriatric organizations, emphasizes a multidisciplinary and nonpharmacologic approach. This strategy involves identifying and addressing the underlying causes of weight loss, optimizing nutrition through diet and supplementation, and promoting exercise. These comprehensive methods offer a more robust and safer path toward improving function, quality of life, and overall health in this vulnerable population. For those with advanced illness, compassionate communication regarding goals of care, rather than aggressive pharmacologic interventions, is paramount.
For more detailed guidance on managing unintentional weight loss in older adults, consult the American Academy of Family Physicians (AAFP) recommendations on avoiding prescription appetite stimulants.
