Pharmacological Management of Undernutrition

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Older patients with a poor response to treatment of underlying causes and nutritional supplementation may benefit from orexigenic agents (Table 5).

Table 5 Orexigenic agents

Megesterol acetate Mirtazapine

Dronabinol (delta-9-tetrahydrocannabinol) Corticosteroids

Loxiglumide (Cholecystokinin antagonist) Oxoglutarate

Anabolic agents (testosterone, anadrol)


Growth hormone


Megestrol acetate is a synthetic progestogen approved for use by the Food and Drug Administration (FDA) as an orexigenic agent in patients with Acquired Immune Deficiency Syndrome (AIDS) and cancer-related anorexia and cachexia. Recent evidence indicates that megesterol acetate is also an effective orexigenic agent in geriatric patients. Thromboembolic disease and adrenal suppression are rare complications, but patients should be monitored closely for these events.

Dronabinol (delta-9-tetrahydrocannabinol), the active ingredient of Cannabis sativa, is another FDA-approved orexigenic agent for use in patients with Acquired Immune Deficiency Syndrome (AIDS). Dronabinol is also an effective orexigenic and antiemetic in patients receiving cancer chemotherapy. Additional evidence indicates that dronabinol induces weight gain in persons with dementia, although research has yet to determine whether weight gain in such patients is due to increased energy intake or reduced agitation with improved behavior and consequently decreased energy expenditure. Side effects of dronabinol in older adults include delirium, euphoria, and increased somnolence. The latter two qualities may favor the use of dronabinol as an orexigenic agent in palliative care.

One third of depressed older adults manifest with weight loss. Effective antidepressant therapy should result in weight gain in this subset of patients. Notably, the choice of antidepressant therapy may influence body weight reuptake. Selective serotonin (5-hydroxytryptamine, 5-HT) inhibitors, such as fluoxetine, can cause significant weight loss at the onset of therapy. Evidence in younger adults suggests that this is a transient phenomenon with baseline body weight being restored as treatment progresses. However, age-related changes in energy regulation and adaptation to chronic disease may delay or prevent return to baseline body weight in older patients. Mirtazapine has proved useful in the management of depressed patients with weight loss. Mirtazapine is a well-tolerated and effective antidepressant that inhibits presynaptic alpha2 adrenergic receptors and postsynaptic 5-HT2 and 5-HT3 receptors. Mirtazapine has been shown to induce an earlier increase in appetite and subsequent weight gain in older depressed persons with weight loss.

Several agents previously touted as effective orexi-genic agents, such as human growth hormone, have fallen out of favor. The administration of human growth hormone to healthy older adults has been shown to increase muscle bulk. However, significant side effects such as carpal tunnel syndrome, gynecomastia and hypoglycemia were noted; furthermore, the increase in muscle bulk failed to produce a parallel increase in muscle strength. Inadequate data regarding the safety and efficacy of growth hormone administration precludes routine clinical use. Similarly, the role of insulin-like growth factor (IGF-I) in the management of undernutrition is questionable. Although the data suggest that exo-genously administered IGF-I may enhance nitrogen retention, gluconeogenesis, and maintenance of normal gastrointestinal function, evidence-based outcome studies are lacking.

Abundant data exist regarding the role of anabolic steroids in the management of undernutrition. However, current evidence supports the restriction of testosterone therapy as an orexigenic agent to hypo-gonadal undernourished men. As a general rule, pharmacological treatment should be considered second-line therapy and reserved for patients who have failed to respond to nonpharmacological measures.

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