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Is Weight Loss in the Nursing Home a Reversible Problem?
Is Weight Loss in the Nursing Home a Reversible Problem? Linda Aoyama, MD, Nancy Weintraub, MD, and David B. Reuben, MD Weight loss in the nursing home is a common problem and is the resultant symptom of complex interactions of multiple disease states and medication reactions, but it can be the instrumental symptom in a downward spiral leading to increasing morbidity and death.1 For this reason, weight loss requires immediate assessment, and its multifactorial nature can make the causes difficult to tease out and difficult to treat. A concerted effort by a multidisciplinary team to investigate the etiology of unintentional weight loss and to develop a plan to deter further weight loss is essential. The minimum data set (MDS), a Centers for Medicare and Medicaid Services mandated resident assessment instrument for the nursing home, defines unintentional weight loss as a 5% loss in actual body weight in 30 days or a 10% loss in 180 days.2 One early study3 in an academic nursing home at a Veterans Administration (VA) medical center found that 60% of 130 patients surveyed had lost weight from admission to time of survey (at least 6 months) and 43% had lost weight during the initial month of institutionalization. Additionally, 70% of nursing home residents lost more than 10 pounds, nearly 40% had lost over 20 pounds, and 4% had lost over 40 pounds at some point during their nursing home stay. In a large crosssectional study of factors associated with low body mass index and weight loss in 6832 nursing home residents using information collected from the MDS, Blaum et al2 found that weight loss, as defined by MDS criteria, occurred in 9.9% of the sample. Weight loss may result in adverse health outcomes in nursing home residents, including increased mortality. Wallace et al4 noted that an annual weight loss of greater than 4% of body weight was associated with a higher mortality rate over a 2-year follow-up period in community-dwelling male veterans older than 65 years. In a retrospective record review,5 subjects with weight loss of more than 5% of body weight in 1 month were 4.6 times more likely to die within 1 year. Murden and Ainslie6 reported that residents in an intermediate-care nursing facility who had a weight loss of 10% of body weight over 6 months had an odds ratio for death in the next 6 months of 14.7. Weight loss of more than 10%
UCLA Multicampus Program in Geriatric Medicine and Gerontology, Los Angeles, CA (L.A., D.B.R.); VA Greater Los Angeles Healthcare System, Sepulveda Geriatric Research, Education & Clinical Center, Sepulveda, CA (N.W.). Address correspondence to Linda Aoyama, MD, UCLA Multicampus Program in Geriatric Medicine and Gerontology, 10945 Le Conte Avenue, Suite 2339, Los Angeles, CA 90095-1687. E-mail: [email protected]
Copyright ©2005 American Medical Directors Association DOI: 10.1016/j.jamda.2005.12.018 S66 Aoyama et al.
over the 3-year study period was also associated with functional decline in another retrospective study.7 WHY DO NURSING HOME PATIENTS LOSE WEIGHT? Determining a cause for weight loss in a nursing home patient can be challenging, as the possible etiologies are numerous. Certain conditions, such as advanced cancer, may not be amenable to treatment. However, many causes of weight loss in the nursing home population can be identified and potentially treated. In a study in a community nursing home, a cause of weight loss was identified in 29 of 30 patients.8 Depression is a commonly encountered problem in the nursing home with estimates of the prevalence of major and minor depression of 6% to 24% and 30% to 50%, respectively.9 Depression was the most common cause of weight loss in both a short-stay and long-stay population.8 In a large study using data from the MDS, depressed behavior increased the odds of having weight loss by about 50%.2 Elderly patients with depression may present with more anorexia and weight loss than younger patients.10 Although direct evidence between resolution of depression and weight gain has not been well studied, effective treatment of depression seems prudent if decreased oral food intake can be attributed to depression. Polypharmacy frequently occurs in the older patient with multiple, complex medical problems, and, not surprisingly, the nursing home population is at considerable risk. Numerous medications have been implicated as contributing to unintentional weight loss in the elderly, often by causing adverse drug effects (Table 1).11 Patients taking digoxin may experience nausea, vomiting, and anorexia. Iron supplements may alter taste sensation or cause swallowing difficulties. Opioid analgesics are commonly known to cause nausea and/or vomiting and can also cause cognitive deficits that impair feeding ability. A retrospective review of 3688 homebound persons receiving oral nutritional supplements found 65% of patients were prescribed at least 1 medication associated with unintentional weight loss.12 Conversely, withdrawal or reduction of psychotropic drugs may also be associated with weight loss.8 Adverse consequences of medications, including weight loss, need to be weighed against clinical benefit. Swallowing disorders and oral-dental problems also need to be considered. Patients susceptible to swallowing dysfunction include those with a history of stroke, Parkinson’s disease, dementia, and other neuromuscular disorders. In an observational study of 200 elderly patients in long-term care in Canada, 19% had dysphagia for solids and/or fluids, which was significantly associated with undernutrition.13 A prospective JAMDA – March 2006
Table 1. Medication-Induced Symptoms That May Compromise Nutritional Status Symptom
Example of Medication
Nausea/vomiting
Antibiotics Nonsteriodal anti-inflammatory drugs (NSAIDs) Opiates Digoxin Theophylline Theophylline Antibiotics Digoxin Metronidazole Calcium-channel blockers Angiotensin-converting enzyme inhibitors Iron supplements Metformin Potassium supplements NSAIDS Iron supplements Alendronate Prednisone Anticholinergic medications Anticholinergic agents Sympathomimetic agents Sedatives Opiates Psychotropic agents Laxatives Antibiotics Sertraline Theophylline Thyroxine Natural supplements: thyroid extracts, ephedrine
Anorexia Hypoageusia
Dysphagia
Early satiety Reduced feeding ability Diarrhea
Hypermetabolism
Reprinted with permission from Clin Geriatr Med.11 Copyright 2002, Elsevier.
study14 of nursing home residents receiving oral supplements highlights the need for physicians to have a high index of suspicion for patients at risk for dysphagia. Twenty of 29 patients had some degree of dysphagia on bedside swallow evaluation; only 4 of the patients had been referred for evaluation prior to the study. With regard to oral-dental factors, Blaum et al2 found that chewing problems were associated with both low body mass index and weight loss. In a VA study15 at a Geriatric Rehabilitation Unit, the number of general oral problems was the best predictor of significant weight loss within 1 year prior to admission, among 10 other variables that included income, age, and adequacy of nutrient intake. In contrast, another study16 of institutionalized patients with dementia found no difference in weight changes during 3 months among patients with dentures, edentulous without dentures, and those who were dentate. Patients who depend on feeding assistance are at risk for weight loss. In an early study at an academic nursing home at the VA, 24% of patients required total assistance in feeding.3 Additionally, one third of the total-assist feeders were 20% below average body weight compared with one tenth of the self- or partial-assist feeders. Blaum et al2 found that eating SUPPLEMENT
dependency increased the risk of having low body mass index or weight loss by 1.5 to 2 times. In a prospective study of 61 newly admitted nursing home patients, 54% were malnourished based on biochemical and anthropometric measurements.17 During the study period that averaged 76 days, 37% of patients continued to be malnourished; these patients differed from the nonmalnourished group by consuming less of their diet and requiring more feeding assistance. A substantial portion of nursing home patients have dementia and are at risk for weight loss. One population-based study from the United Kingdom reported the prevalence of dementia in an institutional setting to be 62%.18 Alzheimer’s disease, in particular, has been associated with weight loss both in the early and later stages of disease.19 Inadequate caloric intake in Alzheimer’s disease is likely multifactorial with contributions from impaired appetite, behavioral issues (food refusal, apathy), apraxia, and problems with chewing or swallowing.19 Several hypotheses have been proposed to explain the weight loss in dementia: failure of body weight regulation, higher resting energy expenditure, hypermetabolism or increased energy expenditure, and self-feeding difficulties.20 Occasionally, certain medical conditions (eg, infection, postoperative states) arise that require patients to meet increased nutritional requirements. In a vicious cycle, patients with malnutrition are more prone to infection; and infection, with its increased metabolic demand, contributes to malnutrition.21 Nursing home patients with chronic illness, such as those with severe chronic obstructive pulmonary disease who use accessory muscles for breathing, have increased energy needs.22 Optimal management of wounds often involves ensuring adequate nutrition.23 Several other issues merit discussion. Food in the nursing home may not be palatable because of restrictive dietary prescriptions or because of inadequate funding for high-quality or a variety of foods. Social issues, such as not honoring ethnic or personal food preferences and dining in isolation, can also contribute to unintentional weight loss. IS WEIGHT LOSS IN THE NURSING HOME TREATABLE? Behavioral/Nondietary Measures One major issue in the nursing home centers around having adequate staffing with proper training for residents who require feeding assistance. In a 4-year anthropological study of 100 nursing home residents who were eating poorly, KayserJones and Schell24 found that inadequate staffing and lack of supervision at mealtimes adversely impacted eating behavior. Simmons et al25 showed that under optimal mealtime feeding assistance, including one-to-one, continuous assistance, 50% of nursing home patients improved their oral food and fluid intake. However, such assistance required more staffing time, an average of 38 minutes per resident per meal compared to the typical 9 minutes. The intervention of optimal feeding assistance occurred over a 2-day period, thus this study was not designed to correlate feeding assistance with weight gain. Potential ways to improve mealtime assistance include enlistAoyama et al. S67
ing family members, establishing shifts that allow for additional coverage with meals, proper education and training of staff about key issues such as dysphagia, and professional oversight.24 Several behavioral and environmental measures may improve the nutritional status of patients residing in the nursing home. A 1-year parallel group intervention study in a nursing home in the Netherlands focused on improving meal ambiance by targeting the physical environment in the dining room, food service, and the organization of the nursing staff assistance.26 Interventions included plants or flowers on the table, sufficient lighting, background music, trays and covers removed from the tables, simultaneous start of meal per table, between-meal beverages, rescheduling staff to provide enough nurses at mealtime, and limiting medication delivery prior to the meal. Those in the intervention group (n ⫽ 12) who completed the study had a statistically significant mean body weight increase of 3.3 kg, while the control group (n ⫽ 10) remained stable, but these findings were limited by an overall drop-out rate that approximated 42%. Many of the recommendations for improving the mealtime experience in the nursing home are based on what makes sense practically, although there is no firm evidence to indicate that these measures will result in weight gain. Some authors recommend the use of a semicircular table to allow 1 nursing aide to feed several dependent feeders at one time.22 Smaller, more frequent meals and between-meal snacks may be beneficial for residents with early satiety or those who fatigue easily. Honoring food choices, providing a varied diet,27 and reducing dietary restrictions28 may make meals more appetizing and improve food intake. Flavor enhancers may help to combat age-related losses of taste and smell.29 The dining room should be made as pleasant as possible with proper lighting, comfortable temperature, and minimizing disruptions from agitated patients.30 For patients with functional deficits, an occupational therapist may provide appropriate assistive devices to maximize independence with feeding (eg, heavy-handled utensils). In a nursing home patient noted to have swallowing or chewing problems, consultation with the appropriate specialist (eg, dentist, speech pathologist, dietician, gastroenterologist) is advised. Oral Supplements Health care providers frequently prescribe oral supplements (OS) for older patients with weight loss. These have been studied in a variety of settings. Following a femur fracture, patients in the hospital receiving OS for 1 month experienced lower complication rates and fewer deaths.31Patients who took OS for 6 months after hospitalization had improved functional status.32 A systematic review from the Cochrane Library concluded that there is a small weight gain and mortality benefit from oral supplements for elderly patients, although these findings require further investigation since most trials of nutritional supplements have poor study quality.33 In nursing homes, oral supplements are commonly employed to increase caloric intake in those who are undernourished or losing weight. In a retrospective, case-control study of OS given in 2 nursing homes, Johnson et al34 found that S68 Aoyama et al.
patients lost an average of 8% of their admission weight before OS were begun. Once OS were started, weight loss stabilized. Additionally, 36 of 56 patients slowly regained weight over 9 to 10 months to approximate their admission weight. In a prospective study from a nursing home in France,35 malnourished patients identified by the mini nutritional assessment received oral nutritional supplements at unspecified times and gained a statistically significant 1.5 ⫾ 0.4 kg with increased total calorie intake at the end of the 60-day study. WoutersWesseling et al36 conducted a randomized double-blind placebocontrolled study in 42 patients with dementia living in a psycho-geriatric nursing home. After the 12-week study period, the group that received the liquid nutrition supplement, which was given between meals, gained a statistically significant 1.4 ⫾ 2.4 kg from baseline, while the control group lost 0.8 ⫾ 3.0 kg, although the difference was not statistically significant. No significant differences were noted in bowel function or change in activities of daily living between the groups. Although daily dietary intake was not measured during the study, the authors postulated that the supplement increased total nutritional intake and contributed to the increase in body weight. However, a study by Fiatarone Singh et al37 in frail institutionalized elders suggested that oral supplements for 10 weeks did not augment total caloric intake but instead, was offset by a simultaneous reduction in voluntary food intake. Based on one study, which showed energy intake was higher when a nutritional supplement was administered 1 hour or more before meals, OS should be taken between meals.38 Kayser-Jones et al14 reported in a prospective study of the use of OS in nursing homes that only 9 of 29 residents were served the correct number and type of supplement, only 2 residents consumed the full amount of supplement, and nearly half of the residents experienced continued weight loss. As the data on the use of OS in the nursing home setting are conflicting, more studies are needed to elucidate how to optimally use and monitor efficacy of oral supplements in the nursing home. Appetite Stimulants Cyproheptadine Cyproheptadine, an antihistamine, was not effective over placebo in increasing weight in adults (median age 65 years) with advanced cancer in a double-blind, placebo-controlled, randomized trial.39 Additionally, the cyproheptadine group reported more side effects including dizziness, sedation, and dry mouth. We are not aware of any studies evaluating cyproheptadine as an appetite stimulant specifically in the elderly. Dronabinol Dronabinol is a cannabinoid approved as a treatment for anorexia associated with weight loss in AIDS patients. In a multicenter, randomized, double-blind, placebo-controlled trial, Beal et al40 studied the effects of dronabinol 2.5 mg bid versus placebo for 6 weeks in 139 patients with AIDS-related anorexia and weight loss. The AIDS patients randomized to dronabinol showed improvements in appetite and mood, decreased nausea, and stabilized weight. The dronabinol-treated JAMDA – March 2006
group also experienced more euphoria, dizziness, thinking abnormalities, and somnolence. Dronabinol has only been studied to a limited extent in older patients. In a placebo-controlled crossover design, dronabinol was studied in 15 patients with probable Alzheimer’s dementia who exhibited food refusal.41 Weight gain during treatment with dronabinol was minimally improved (approximately 1.5 pounds) compared to placebo. There was no difference in caloric intake between the 2 arms. During dronabinol treatment, disturbed behavior decreased, and this finding persisted during the placebo period, possibly due to longacting metabolites. The weight gain was postulated to have been caused by decreased agitation. In addition, 1 of 15 patients on dronabinol experienced a seizure, whereas others were noted to have tiredness, somnolence, and euphoria. Until further studies are conducted, dronabinol cannot be considered for routine treatment of weight loss in this population. Megestrol acetate Megestrol acetate (MA), a synthetic derivative of the natural steroid progesterone, has been shown to increase appetite, contribute to weight gain, and improve quality of life in clinical trials in the oncology and AIDS literature.42– 48 The data supporting megestrol acetate for treatment of geriatric anorexia and cachexia, however, are sparse. Two small case series suggested a small weight gain associated with MA.49,50 Yeh et al51 conducted the only randomized, double-blind, placebo-controlled trial in a nursing home with 69 patients randomized to MA 800 mg/d versus placebo for 12 weeks with an additional 13-week follow-up off the drug. Eighteen (26.1%) patients were excluded from efficacy analysis as they violated entry criteria or withdrew from the study. At the end of 12 weeks, there was no statistically significant mean weight change between groups. At week 20, a statistically significant mean weight gain of ⫹2.45 kg in the MA group versus – 0.41 kg in the placebo emerged. Other significant benefits in the MA-treated group included improved appetite, improved sense of well-being and improved enjoyment scores from baseline to 12 weeks. MA failed to increase weight in a subset (representing 38% of participants) who tended to be more frail, to have more concurrent medical conditions, to be taking more than 10 medications, and to be more wasted. The study reported no statistically significant differences between the 2 groups in regard to adverse events directly related to drug treatment. Possible adverse effects with MA include fluid retention, diarrhea, reversible decrease in serum cortisol levels, and thromboembolism. From 2 retrospective chart reviews, rates of deep vein thromboses in nursing home patients receiving MA were reported to range from 4.9% to 32%.52,53 MA should be used with caution in nonambulatory residents or those at risk for venous thromboembolism. A few unresolved issues surround the use of MA in nursing home patients. One issue is identifying which patients are most likely to respond. In the Yeh et al study,51 greater than one third of patients were nonresponders and those tended to be the more frail patients. Also, noted in the Yeh et al study,51 MA had a delayed effect on weight gain with the statistically SUPPLEMENT
significant weight gain occurring 2 months following discontinuation of MA. Although the mechanism by which MA leads to weight gain is unknown, one postulated mechanism is that MA leads to a reduction in the inflammatory cytokines that have anorexia-promoting properties.54 In a concurrent study,55 Yeh et al compared cytokine levels in patients taking MA and placebo but did not find a statistically significant difference between groups at 12 weeks. However, there was a statistically significant negative correlation between changes in cytokine levels and changes in weight, eg, increased weight correlated with decreased levels of 2 of the 4 cytokines measured. Another issue involves whether providing an appetite stimulant without other supportive measures, including increased access to food or feeding assistance, is adequate. In a prospective, preliminary trial in the nursing home, Simmons et al56 found that MA improved oral food and fluid intake under optimal mealtime feeding assistance but not under usual nursing home care. For a subset of nursing home patients, MA can improve appetite and lead to weight gain. Further studies will need to elucidate which patients are most likely to respond and when in the course of weight loss MA should be initiated, especially given that weight gain may not occur for months. Other A variety of other agents have been investigated to stimulate appetite or increase weight. Pentoxifylline and thalidomide both decrease tumor necrosis factor-␣ and have been studied in HIV-infected patients with varying results.57 Testosterone replacement in older men has been shown to increase muscle mass.58 Patients with advanced lung cancer who were randomized to receive the anabolic agent nandrolone, in addition to combination chemotherapy, showed a trend for less severe weight loss.59 Although some studies suggested growth hormone may be beneficial in malnourished older persons,60,61 a subsequent trial in critically ill, malnourished patients found an increased rate of death in patients treated with growth hormone.62 Glucocorticoids have been used to improve appetite and mood in cancer cachexia but side effects often limit use to palliative care. In one study, ornithine oxoglutarine was shown to increase appetite and promote weight gain in older patients following acute illness.63 Psychotropic Medications Psychiatric conditions, such as depression, anxiety, and behavioral disturbances associated with dementia are prevalent in a nursing home population. Medication selection is often influenced by side effect profile, including effects on weight and appetite. Antidepressant Medication Many clinicians attribute weight gain to tricyclic antidepressant (TCA) therapy and weight loss to selective serotonin reuptake inhibitor (SSRI) therapy. However, there are few data to support these beliefs.64,65 In a retrospective chart review in a VA setting, Brymer and Winograd65 reported that 47% (7 of 15) of outpatients older than 75 years taking fluoxetine lost more than 5% of their initial body weight Aoyama et al. S69
compared with none (0 of 20) of those receiving TCAs. In a large retrospective cohort study using the MDS, Rigler et al66 found that SSRI use was associated with both weight gain and weight loss of marginal significance and that TCA use was not associated with clinically important weight gain. Additionally, the differences in mean weight changes between SSRIs, TCA, and other antidepressants were small and not clinically significant for most patients. Mirtazapine, an antidepressant with noradrenergic and serotonergic effects, has been characterized as a “1-stop” antidepressant because of its reported benefits on several depression-related symptoms including insomnia and weight loss. Fawcett and Barkin67 reviewed clinical trials of mirtazapine and reported a statistically significant increase in appetite and weight gain from pooled data in mirtazapine-treated patients over placebo. In a retrospective chart review of 50 nursing home patients treated with mirtazapine or sertraline for 4 months for major depression or dementia with depression, weight gain was similar in both.68 In contrast, 2 randomized, double-blind clinical trials69,70 showed mirtazapine to have positive effects on weight gain and improved depression scale scores. In an 8-week, comparative trial in 246 depressed elderly patients, 10.9% of patients on mirtazapine gained weight versus none on paroxetine, which was statistically significant.69 The mean body weight in the mirtazapine group increased approximately 1.7 kg during the study period. Additionally, 5 patients in the mirtazapine group experienced a greater than 7% gain from baseline in contrast to none in the paroxetine group. Halikas70 conducted a 6-week study comparing placebo, trazodone, and mirtazapine in 150 older adults with depression. Twenty-four percent of the mirtazapine group reported increased appetite as compared with 4% of placebo-treated group and 6% in the trazodone group. The group on mirtazapine showed a mean weight gain of 1.3 kg from baseline. Mirtazapine has been shown to improve appetite and contribute to a modest weight gain in older adults undergoing treatment for depression. It is uncertain whether mirtazapine will have a similar effect in nondepressed patients. Antipsychotic Medication Conventional antipsychotic medications have been associated with significant weight gain in adults.71 Atypical antipsychotics were developed to have less extrapyramidal side effects but have also been noted to contribute to weight gain in adult populations.72,73 Elderly patients, including those in nursing homes, are commonly prescribed antipsychotic medications.74 In a trial comparing varying doses of olanzapine versus placebo to manage behavior in patients with Alzheimer’s disease, no significant weight changes were seen.75Although atypical antipsychotics have been shown to increase weight in younger populations, it is uncertain whether they have a similar effect in an older population. SUMMARY AND CONCLUSION Undernutrition and weight loss are complex issues in the nursing home. With multiple medical, psychological, and social variables in the nursing home patient, health care providers should develop a mechanism to identify patients at risk for undernutrition and weight loss. Then, the resources of an interS70 Aoyama et al.
disciplinary team would ideally be implemented to determine an etiology for the weight loss. Specific measures should be taken to address the determined cause, for example antidepressants for depressed patients. Behavior interventions, such as ensuring adequate feeding assistance and encouraging socialization at meal times, are simple ways to improve the nutritional status of nursing home patients. Encouraging family members to bring in favorite foods; making available frequent, high-caloric snacks; and ordering oral nutritional supplements are several ways to potentially increase oral food and calorie intake. If anorexia is considered to be a significant factor in weight loss, a trial of an appetite stimulant, such as megestrol acetate, may be attempted. In depressed older patients, mirtazapine appears to have some weight gain benefits. Antipsychotics have been shown to increase weight in younger patients, but convincing data in older patients are not yet available. Although identifying and addressing the cause for weight loss is the initial step, various interventions are often employed concomitantly. Often, multiple, simultaneous interventions will be necessary, as no single intervention will be successful in all patients. Of note, when patients’ family members were queried about preferences to improve their relative’s oral food and fluid intake, they ranked the following interventions from most to least desirable: (1) improve quality of food; (2) improve quality and quantity of feeding assistance; (3) provide multiple small meals and snacks throughout the day; (4) place resident in preferred dining location; (5) provide an oral liquid nutritional supplement between meals; and (6) provide medication to stimulate appetite.76 Clearly, options exist to improve and maximize the nutritional health of nursing home patients, but more research is needed to explore the causes of weight loss in the very old, which may facilitate the development of specific, targeted interventions. REFERENCES 1. Sullivan DH, Morley JE, Johnson LE, et al. The GAIN (Geriatric Anorexia Nutrition) Registry: The impact of appetite and weight on mortality in a long-term care population. J Nutr Health Aging 2002;6: 275–281. 2. Blaum CS, Fries BE, Fiatarone MA. Factors associated with low body mass index and weight loss in nursing home residents. J Gerontol 1995: 50A:M162–M168. 3. Silver AJ, Morley JE, Strome LS, et al. Nutritional status in an academic nursing home. J Am Geriatr Soc 1988;36:487– 491. 4. Wallace JI, Schwartz RS, LaCroix, AZ, Uhlmann RF, Pearlman RA. Involuntary weight loss in older outpatients: Incidence and clinical significance. J Am Geriatr Soc 1995;43:329 –337. 5. Ryan C, Bryant, E, Eleazer P, et al. Unintentional weight loss in longterm care: Predictor of mortality in the elderly. South Med J 1995;88: 721–724. 6. Murden RA, Ainslie NK. Recent weight loss is related to short-term mortality in nursing homes. J Gen Intern Med 1994;9:648 – 650. 7. Chang JI, Katz PR, Ambrose P. Weight loss in nursing home patients: Prognostic implications. J Fam Pract 1990;30:671– 674. 8. Morley JE, Kraenzle D. Causes of weight loss in a community nursing home. J Am Geriatr Soc 1994;42:583–585. 9. Katz IR, Parmelee PA. Depression in elderly patients in residential care settings. In: Diagnosis and treatment of depression in late life: Results of the NIH Consensus Development Conference. Schneider LS, Reynolds CV III, editors. Washington, DC: American Psychiatric Press; 1994. p. 463– 490. 10. Fitten LJ, Morley JE, Gross PL, Petry SD, Coke KD. Depression. J Am Geriatr Soc 1989; 37:459 – 472. JAMDA – March 2006
11. Wilson MM. Undernutrition in medical outpatients. Clin Geriatr Med 2002;18:759 –771. 12. Golden AG, Petropoulos JB, Silverman MA, Musson N, Hamdan K. The use of oral nutritional supplements and anorexigenic medications in homebound older adults. J Am Geriatr Soc 2003;51:724 –726. 13. Keller HH. Malnutrition in institutionalized elderly: How and why? J Am Geriatr Soc 1993;41:1212–1218. 14. Kayser-Jones J, Schell ES, Porter C, et al. A prospective study of the use of liquid oral dietary supplements in nursing homes. J Am Geriatr Soc 1998;46:1378 –1386. 15. Sullivan DH, Martin W, Flaxman N, Hagen JE. Oral health problems and involuntary weight loss in a population of frail elderly. J Am Geriatr Soc 1993;41:725–731. 16. Horn VJ, Hodge WC. Treuer JP. Dental condition and weight loss in institutionalized demented patients. Spec Care Dentist 1994;14:108 – 111. 17. Thomas DR, Verdery RB, Gardner L, et al. A prospective study of outcome from protein-energy malnutrition in nursing home residents. JPEN 1991;15:400 – 404. 18. Matthews FE, Dening T. Prevalence of dementia in institutional care. Lancet 2002;360:225–226. 19. Mazzali G, Bissoli L, Gambina S, et al. Energy balance in Alzheimer’s Disease. J Nutr Health Aging 2002;6:247–253. 20. Heller HH, Gibbs, AJ, Boudreau LD, et al. Prevention of weight loss in dementia with comprehensive nutritional treatment. J Am Geriatr Soc 2003;51:945–951. 21. Gavazzi G, Krause KH. Ageing and infection. Lancet Infect Dis 2002;2: 659 – 666. 22. Morley JE, Silver AJ. Nutrition. In: Besdine RW, Rubenstein LZ, Snyder L, editors. Medical care of the nursing home resident. Philadelphia: American College of Physicians; 1996. p. 117–129. 23. Mathus-Vliege EM. Old age, malnutrition, and pressure sores: An illfated alliance. J Gerontol A Biol Sci Med Sci 2004;59:355–360. 24. Kayser-Jones J, Schell ES. Staffing and the mealtime experience of nursing home residents on a special care unit. Am J Alzheimers Dis Other Demen 1997;12:67–72. 25. Simmons SF, Osterweil D, Schnelle JF. Improving food intake in nursing home residents with feeding assistance: A staffing analysis. J Gerontol Med Sci 2001;56A:M790 –M794. 26. Mathey MF, Vanneste VG, deGraaf C, et al. Health effect of improved meal ambiance in a Dutch nursing home: A 1-year intervention study. Prev Med 2001;32:416 – 423. 27. Bernstein MA, Tucker KL, Ryan ND, et al. Higher dietary variety is associated with better nutritional status in frail elderly people. J Am Diet Assoc 2002;102:1096 –1104. 28. Buckler DA, Kelber ST, Goodwin JS. The use of dietary restrictions in malnourished nursing home patients. J Am Geriatr Soc 1994;42:1100 – 1102. 29. Mathey MF, Siebelink E, de Graaf C, et al. Flavor enhancement of food improves dietary intake and nutritional status of elderly nursing home residents. J Gerontol A Biol Sci Med Sci 2001;56:M200 –M205. 30. Fabiny AR and Kiel DP. Assessing and treating weight loss in nursing home residents. Clin in Geriatr Med 1997:13:737–751. 31. Delmi M, Rapin CH, Bengoa JM, et al. Dietary supplementation in elderly patients with fractured neck of femur. Lancet 1990;355:1013– 1016. 32. Volkert D, Hubsch S, Oster P. Nutritional support and functional status in undernourished geriatric patients during hospitalization and 6 months follow-up. Aging Clin Exp Res 1996;8:386 –395. 33. Milne AC, Potter J, Avenell A. Protein and energy supplementation in elderly people at risk from malnutrition (Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software. 34. Johnson LE, Dooley PA, Gleick JB. Oral nutritional supplement use in elderly nursing home patients. J Am Geriatr Soc 1993:41:947–952. 35. Lauque S, Arnaud-Battandier F, Mansourian R, et al. Protein-energy oral supplementation in malnourished nursing-home residents: A controlled trial. Age Ageing 2000;29:51–56. SUPPLEMENT
36. Wouters-Wesseling W, Wouters AEJ, Kleijer CN, et al. Study of the effect of a liquid nutrition supplement on the nutritional status of psycho-geriatric nursing home patients. Eur J Clin Nutr 2002;56:245– 251. 37. Fiatarone Singh MA, Bernstein MA, Ryan AD, et al. The effect of oral nutritional supplements on habitual dietary quality and quantity in frail elders. J Nutr Health Aging 2000;4:5–12. 38. Wilson MM, Purushothaman R, Morley JE. Effect of liquid dietary supplements on energy intake in the elderly. Am J Clin Nutr 2002;75: 944 –947. 39. Cardinal CG, Loprinzi CL, Schaid DJ, et al. A controlled trial of cyproheptadine in cancer patients with anorexia and/or cachexia. Cancer 1990;65:2657–2662. 40. Beal JE, Olson R, Laubenstein L, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 1995;10:89 –97. 41. Volicer L, Stelly M, Morris J, et al. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 1997;12:913–919. 42. Tchekmedyian NS, Tait N, Moody M, Aisner J. High-dose megestrol acetate. JAMA 1987;257:1195–1198. 43. Tchekmedyian NS, Hickman M, Siau J, et al. Megestrol acetate in cancer anorexia and weight loss. Cancer 1992;69:1268 –1274. 44. Feliu J, Gonzalez-Baron M, Berrocal A, et al. Usefulness of megestrol acetate in cancer cachexia and anorexia. Am J Clin Oncol 1992;15:436 – 440. 45. Skarlos DV, Fountzilas G, Pavlidis N, et al. Megestrol acetate in cancer patients with anorexia and weight loss. Acta Oncologica 1993;32:37– 41. 46. Loprinzi CL, Bernath AM, Malliard JA, et al. Phase III evaluation of 4 doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia. Oncology 1994;51(Suppl 1):2–7. 47. Von Roenn JH, Armstrong D, Kotler DP, et al. Megestrol acetate in patients with AIDS-related cachexia. Ann Intern Med 1994:121:393– 339. 48. Oster MH, Enders SR, Samuels SJ, et al. Megestrol acetate in patients with AIDS and cachexia. Ann Intern Med 1994;121:400 –508. 49. Castle S, Nguyen C, Joaquin A, et al. Megestrol acetate suspension therapy in the treatment of geriatric anorexia/cachexia in nursing home patients. J Am Geriatr Soc 1995;43:835– 836. 50. Raney MS, Anding R, Fay V, Polk G. A pilot study to assess the use of megesterol acetate to promote weight gain in frail elderly persons in long-term care. J Am Med Dir Assoc 2000;1:154 –158. 51. Yeh SS, Wu SY, Lee TP, et al. Improvement in quality-of-life measures and stimulation of weight gain after treatment with megestrol acetate oral suspension in geriatric cachexia: Results of a double-blind, placebocontrolled study J Am Geriatr Soc 2000;48:485– 492. 52. Kropsky B, Shi Y, Cherniack EP. Incidence of deep-venous thrombosis in nursing home residents using megestrol acetate. J Am Med Dir Assoc 2003;4:255–256. 53. Bolen JC, Andersen RE, Bennett RG. Deep vein thrombosis as a complication of megestrol acetate therapy among nursing home residents. J Am Med Dir Assoc 2000;48:248 –252. 54. Morley JE. Orexigenic and anabolic agents. Clin Geriatr Med 2002;18: 853– 866. 55. Yeh SS, Wu S-Y, Levine DM, et al. The correlation of cytokine levels with body weight after megestrol acetate treatment in geriatric patients. J Gerontol Med Sci 2001;56A:M48 –M54. 56. Simmons SF, Walker KA, Osterweil D. The effect of megestrol acetate on oral food and fluid intake in nusing home residents: A pilot study. J Am Med Dir Assoc 2004;5:24 –30. 57. Yeh SS, Schuster MW. Geriatric cachexia: The role of cytokines. Am J Clin Nutr 1999;70:183–197. 58. Snyder PJ, Peachey H, Berlin JA, et al. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab 2000;85:2670 – 2677. 59. Chlebowski RT, Herrold J, Ali I, et al. Influence of nandrolone decanoate on weight loss in advanced non-small cell lung cancer. Cancer 1986;58:183–186. Aoyama et al. S71
60. Kaiser FE, Silver AJ, Morley JE. The effect of recombinant human growth hormone on malnourished older individuals. J Am Geriatr Soc 1991;39:235–240. 61. Chu LW, Dietz R, Ranke-Lam KSL, et al. A randomized controlled trial of low-dose recombinant human growth hormone in the treatment of malnourished elderly medical patients. J Clin Endocrinol Metab 2001; 86:1913–1920. 62. Osterziel KJ, Dietz R, Ranke MB. Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 2000; 342:134 –135. 63. Brocker P, Vellas B, Albarede JL, Poynard T. A two-centre, randomized, double-blind trial of ornithine oxoglutarate in 194 elderly, ambulatory, convalescent subjects. Age Ageing 1994;23;303–306. 64. Feighner JP, Cohn JB. Double-blind comparative trials of fluoxetine and doxepin in geriatric patients with major depressive disorder. J Clin Psych 1985;46:20 –25. 65. Brymer C, Winograd CH. Fluoxetine in elderly patients: Is there cause for concern? J Am Geriatr Soc 1992;40:902–905. 66. Rigler SK, Webb MJ, Redford L, et al. Weight outcomes among antidepressant users in nursing facilities. J Am Geriatr Soc 2001;49:49 –55. 67. Fawcett J, Barkin RL. Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression. J Affect Disord 1998;51:267–285.
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68. Goldberg RJ. Weight change in depressed nursing home patients on mirtazapine [letter]. J Am Geriatr Soc 2002;50:1461. 69. Schatzberg AF, Kremer C, Rodrigues HE, et al. Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients. Am J Psychiatry 2002;10:541–550. 70. Halikas JA. Org 3770 (Mirtazapine) versus Trazodone: A placebo controlled trial in depressed elderly patients. Hum Psychopharmacol 1995; 10:S125–S133. 71. Rockwell WJ, Ellinwood EH, Trader DW. Psychotropic drugs promoting weight gain: Health risks and treatment implications. South Med J 1983; 76:1407–1412. 72. Gupta S, Droney T, Al-Samarrai S, et al. Olanzapine: Weight gain and therapeutic efficacy. J Clin Psychopharmacol 1999;19:273–5. 73. Wirshing DA, Wirshing WC, Kysar L, et al. Novel antipsychotics: Comparison of weight gain liabilities. J Clin Psychiatry 1999;60:358 – 363. 74. Lasser RA, Sunderland T. Newer psychotropic medication use in nursing home residents. J Am Geriatr Soc 1998;46:202–207. 75. Street JS, Clark S, Gannon KS, et al. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities. Arch Gen Psychiatry 2000;57:968 –976. 76. Simmons SF, Lam HY, Rao G, Schnelle JF. Family members’ preferences for nutrition interventions to improve nursing home residents oral food and fluid intake. J Am Geriatr Soc 2003;51:69 –74.
JAMDA – March 2006
UCLA Multicampus Program in Geriatric Medicine and Gerontology, Los Angeles, CA (L.A., D.B.R.); VA Greater Los Angeles Healthcare System, Sepulveda Geriatric Research, Education & Clinical Center, Sepulveda, CA (N.W.). Address correspondence to Linda Aoyama, MD, UCLA Multicampus Program in Geriatric Medicine and Gerontology, 10945 Le Conte Avenue, Suite 2339, Los Angeles, CA 90095-1687. E-mail: [email protected]
Copyright ©2005 American Medical Directors Association DOI: 10.1016/j.jamda.2005.12.018 S66 Aoyama et al.
over the 3-year study period was also associated with functional decline in another retrospective study.7 WHY DO NURSING HOME PATIENTS LOSE WEIGHT? Determining a cause for weight loss in a nursing home patient can be challenging, as the possible etiologies are numerous. Certain conditions, such as advanced cancer, may not be amenable to treatment. However, many causes of weight loss in the nursing home population can be identified and potentially treated. In a study in a community nursing home, a cause of weight loss was identified in 29 of 30 patients.8 Depression is a commonly encountered problem in the nursing home with estimates of the prevalence of major and minor depression of 6% to 24% and 30% to 50%, respectively.9 Depression was the most common cause of weight loss in both a short-stay and long-stay population.8 In a large study using data from the MDS, depressed behavior increased the odds of having weight loss by about 50%.2 Elderly patients with depression may present with more anorexia and weight loss than younger patients.10 Although direct evidence between resolution of depression and weight gain has not been well studied, effective treatment of depression seems prudent if decreased oral food intake can be attributed to depression. Polypharmacy frequently occurs in the older patient with multiple, complex medical problems, and, not surprisingly, the nursing home population is at considerable risk. Numerous medications have been implicated as contributing to unintentional weight loss in the elderly, often by causing adverse drug effects (Table 1).11 Patients taking digoxin may experience nausea, vomiting, and anorexia. Iron supplements may alter taste sensation or cause swallowing difficulties. Opioid analgesics are commonly known to cause nausea and/or vomiting and can also cause cognitive deficits that impair feeding ability. A retrospective review of 3688 homebound persons receiving oral nutritional supplements found 65% of patients were prescribed at least 1 medication associated with unintentional weight loss.12 Conversely, withdrawal or reduction of psychotropic drugs may also be associated with weight loss.8 Adverse consequences of medications, including weight loss, need to be weighed against clinical benefit. Swallowing disorders and oral-dental problems also need to be considered. Patients susceptible to swallowing dysfunction include those with a history of stroke, Parkinson’s disease, dementia, and other neuromuscular disorders. In an observational study of 200 elderly patients in long-term care in Canada, 19% had dysphagia for solids and/or fluids, which was significantly associated with undernutrition.13 A prospective JAMDA – March 2006
Table 1. Medication-Induced Symptoms That May Compromise Nutritional Status Symptom
Example of Medication
Nausea/vomiting
Antibiotics Nonsteriodal anti-inflammatory drugs (NSAIDs) Opiates Digoxin Theophylline Theophylline Antibiotics Digoxin Metronidazole Calcium-channel blockers Angiotensin-converting enzyme inhibitors Iron supplements Metformin Potassium supplements NSAIDS Iron supplements Alendronate Prednisone Anticholinergic medications Anticholinergic agents Sympathomimetic agents Sedatives Opiates Psychotropic agents Laxatives Antibiotics Sertraline Theophylline Thyroxine Natural supplements: thyroid extracts, ephedrine
Anorexia Hypoageusia
Dysphagia
Early satiety Reduced feeding ability Diarrhea
Hypermetabolism
Reprinted with permission from Clin Geriatr Med.11 Copyright 2002, Elsevier.
study14 of nursing home residents receiving oral supplements highlights the need for physicians to have a high index of suspicion for patients at risk for dysphagia. Twenty of 29 patients had some degree of dysphagia on bedside swallow evaluation; only 4 of the patients had been referred for evaluation prior to the study. With regard to oral-dental factors, Blaum et al2 found that chewing problems were associated with both low body mass index and weight loss. In a VA study15 at a Geriatric Rehabilitation Unit, the number of general oral problems was the best predictor of significant weight loss within 1 year prior to admission, among 10 other variables that included income, age, and adequacy of nutrient intake. In contrast, another study16 of institutionalized patients with dementia found no difference in weight changes during 3 months among patients with dentures, edentulous without dentures, and those who were dentate. Patients who depend on feeding assistance are at risk for weight loss. In an early study at an academic nursing home at the VA, 24% of patients required total assistance in feeding.3 Additionally, one third of the total-assist feeders were 20% below average body weight compared with one tenth of the self- or partial-assist feeders. Blaum et al2 found that eating SUPPLEMENT
dependency increased the risk of having low body mass index or weight loss by 1.5 to 2 times. In a prospective study of 61 newly admitted nursing home patients, 54% were malnourished based on biochemical and anthropometric measurements.17 During the study period that averaged 76 days, 37% of patients continued to be malnourished; these patients differed from the nonmalnourished group by consuming less of their diet and requiring more feeding assistance. A substantial portion of nursing home patients have dementia and are at risk for weight loss. One population-based study from the United Kingdom reported the prevalence of dementia in an institutional setting to be 62%.18 Alzheimer’s disease, in particular, has been associated with weight loss both in the early and later stages of disease.19 Inadequate caloric intake in Alzheimer’s disease is likely multifactorial with contributions from impaired appetite, behavioral issues (food refusal, apathy), apraxia, and problems with chewing or swallowing.19 Several hypotheses have been proposed to explain the weight loss in dementia: failure of body weight regulation, higher resting energy expenditure, hypermetabolism or increased energy expenditure, and self-feeding difficulties.20 Occasionally, certain medical conditions (eg, infection, postoperative states) arise that require patients to meet increased nutritional requirements. In a vicious cycle, patients with malnutrition are more prone to infection; and infection, with its increased metabolic demand, contributes to malnutrition.21 Nursing home patients with chronic illness, such as those with severe chronic obstructive pulmonary disease who use accessory muscles for breathing, have increased energy needs.22 Optimal management of wounds often involves ensuring adequate nutrition.23 Several other issues merit discussion. Food in the nursing home may not be palatable because of restrictive dietary prescriptions or because of inadequate funding for high-quality or a variety of foods. Social issues, such as not honoring ethnic or personal food preferences and dining in isolation, can also contribute to unintentional weight loss. IS WEIGHT LOSS IN THE NURSING HOME TREATABLE? Behavioral/Nondietary Measures One major issue in the nursing home centers around having adequate staffing with proper training for residents who require feeding assistance. In a 4-year anthropological study of 100 nursing home residents who were eating poorly, KayserJones and Schell24 found that inadequate staffing and lack of supervision at mealtimes adversely impacted eating behavior. Simmons et al25 showed that under optimal mealtime feeding assistance, including one-to-one, continuous assistance, 50% of nursing home patients improved their oral food and fluid intake. However, such assistance required more staffing time, an average of 38 minutes per resident per meal compared to the typical 9 minutes. The intervention of optimal feeding assistance occurred over a 2-day period, thus this study was not designed to correlate feeding assistance with weight gain. Potential ways to improve mealtime assistance include enlistAoyama et al. S67
ing family members, establishing shifts that allow for additional coverage with meals, proper education and training of staff about key issues such as dysphagia, and professional oversight.24 Several behavioral and environmental measures may improve the nutritional status of patients residing in the nursing home. A 1-year parallel group intervention study in a nursing home in the Netherlands focused on improving meal ambiance by targeting the physical environment in the dining room, food service, and the organization of the nursing staff assistance.26 Interventions included plants or flowers on the table, sufficient lighting, background music, trays and covers removed from the tables, simultaneous start of meal per table, between-meal beverages, rescheduling staff to provide enough nurses at mealtime, and limiting medication delivery prior to the meal. Those in the intervention group (n ⫽ 12) who completed the study had a statistically significant mean body weight increase of 3.3 kg, while the control group (n ⫽ 10) remained stable, but these findings were limited by an overall drop-out rate that approximated 42%. Many of the recommendations for improving the mealtime experience in the nursing home are based on what makes sense practically, although there is no firm evidence to indicate that these measures will result in weight gain. Some authors recommend the use of a semicircular table to allow 1 nursing aide to feed several dependent feeders at one time.22 Smaller, more frequent meals and between-meal snacks may be beneficial for residents with early satiety or those who fatigue easily. Honoring food choices, providing a varied diet,27 and reducing dietary restrictions28 may make meals more appetizing and improve food intake. Flavor enhancers may help to combat age-related losses of taste and smell.29 The dining room should be made as pleasant as possible with proper lighting, comfortable temperature, and minimizing disruptions from agitated patients.30 For patients with functional deficits, an occupational therapist may provide appropriate assistive devices to maximize independence with feeding (eg, heavy-handled utensils). In a nursing home patient noted to have swallowing or chewing problems, consultation with the appropriate specialist (eg, dentist, speech pathologist, dietician, gastroenterologist) is advised. Oral Supplements Health care providers frequently prescribe oral supplements (OS) for older patients with weight loss. These have been studied in a variety of settings. Following a femur fracture, patients in the hospital receiving OS for 1 month experienced lower complication rates and fewer deaths.31Patients who took OS for 6 months after hospitalization had improved functional status.32 A systematic review from the Cochrane Library concluded that there is a small weight gain and mortality benefit from oral supplements for elderly patients, although these findings require further investigation since most trials of nutritional supplements have poor study quality.33 In nursing homes, oral supplements are commonly employed to increase caloric intake in those who are undernourished or losing weight. In a retrospective, case-control study of OS given in 2 nursing homes, Johnson et al34 found that S68 Aoyama et al.
patients lost an average of 8% of their admission weight before OS were begun. Once OS were started, weight loss stabilized. Additionally, 36 of 56 patients slowly regained weight over 9 to 10 months to approximate their admission weight. In a prospective study from a nursing home in France,35 malnourished patients identified by the mini nutritional assessment received oral nutritional supplements at unspecified times and gained a statistically significant 1.5 ⫾ 0.4 kg with increased total calorie intake at the end of the 60-day study. WoutersWesseling et al36 conducted a randomized double-blind placebocontrolled study in 42 patients with dementia living in a psycho-geriatric nursing home. After the 12-week study period, the group that received the liquid nutrition supplement, which was given between meals, gained a statistically significant 1.4 ⫾ 2.4 kg from baseline, while the control group lost 0.8 ⫾ 3.0 kg, although the difference was not statistically significant. No significant differences were noted in bowel function or change in activities of daily living between the groups. Although daily dietary intake was not measured during the study, the authors postulated that the supplement increased total nutritional intake and contributed to the increase in body weight. However, a study by Fiatarone Singh et al37 in frail institutionalized elders suggested that oral supplements for 10 weeks did not augment total caloric intake but instead, was offset by a simultaneous reduction in voluntary food intake. Based on one study, which showed energy intake was higher when a nutritional supplement was administered 1 hour or more before meals, OS should be taken between meals.38 Kayser-Jones et al14 reported in a prospective study of the use of OS in nursing homes that only 9 of 29 residents were served the correct number and type of supplement, only 2 residents consumed the full amount of supplement, and nearly half of the residents experienced continued weight loss. As the data on the use of OS in the nursing home setting are conflicting, more studies are needed to elucidate how to optimally use and monitor efficacy of oral supplements in the nursing home. Appetite Stimulants Cyproheptadine Cyproheptadine, an antihistamine, was not effective over placebo in increasing weight in adults (median age 65 years) with advanced cancer in a double-blind, placebo-controlled, randomized trial.39 Additionally, the cyproheptadine group reported more side effects including dizziness, sedation, and dry mouth. We are not aware of any studies evaluating cyproheptadine as an appetite stimulant specifically in the elderly. Dronabinol Dronabinol is a cannabinoid approved as a treatment for anorexia associated with weight loss in AIDS patients. In a multicenter, randomized, double-blind, placebo-controlled trial, Beal et al40 studied the effects of dronabinol 2.5 mg bid versus placebo for 6 weeks in 139 patients with AIDS-related anorexia and weight loss. The AIDS patients randomized to dronabinol showed improvements in appetite and mood, decreased nausea, and stabilized weight. The dronabinol-treated JAMDA – March 2006
group also experienced more euphoria, dizziness, thinking abnormalities, and somnolence. Dronabinol has only been studied to a limited extent in older patients. In a placebo-controlled crossover design, dronabinol was studied in 15 patients with probable Alzheimer’s dementia who exhibited food refusal.41 Weight gain during treatment with dronabinol was minimally improved (approximately 1.5 pounds) compared to placebo. There was no difference in caloric intake between the 2 arms. During dronabinol treatment, disturbed behavior decreased, and this finding persisted during the placebo period, possibly due to longacting metabolites. The weight gain was postulated to have been caused by decreased agitation. In addition, 1 of 15 patients on dronabinol experienced a seizure, whereas others were noted to have tiredness, somnolence, and euphoria. Until further studies are conducted, dronabinol cannot be considered for routine treatment of weight loss in this population. Megestrol acetate Megestrol acetate (MA), a synthetic derivative of the natural steroid progesterone, has been shown to increase appetite, contribute to weight gain, and improve quality of life in clinical trials in the oncology and AIDS literature.42– 48 The data supporting megestrol acetate for treatment of geriatric anorexia and cachexia, however, are sparse. Two small case series suggested a small weight gain associated with MA.49,50 Yeh et al51 conducted the only randomized, double-blind, placebo-controlled trial in a nursing home with 69 patients randomized to MA 800 mg/d versus placebo for 12 weeks with an additional 13-week follow-up off the drug. Eighteen (26.1%) patients were excluded from efficacy analysis as they violated entry criteria or withdrew from the study. At the end of 12 weeks, there was no statistically significant mean weight change between groups. At week 20, a statistically significant mean weight gain of ⫹2.45 kg in the MA group versus – 0.41 kg in the placebo emerged. Other significant benefits in the MA-treated group included improved appetite, improved sense of well-being and improved enjoyment scores from baseline to 12 weeks. MA failed to increase weight in a subset (representing 38% of participants) who tended to be more frail, to have more concurrent medical conditions, to be taking more than 10 medications, and to be more wasted. The study reported no statistically significant differences between the 2 groups in regard to adverse events directly related to drug treatment. Possible adverse effects with MA include fluid retention, diarrhea, reversible decrease in serum cortisol levels, and thromboembolism. From 2 retrospective chart reviews, rates of deep vein thromboses in nursing home patients receiving MA were reported to range from 4.9% to 32%.52,53 MA should be used with caution in nonambulatory residents or those at risk for venous thromboembolism. A few unresolved issues surround the use of MA in nursing home patients. One issue is identifying which patients are most likely to respond. In the Yeh et al study,51 greater than one third of patients were nonresponders and those tended to be the more frail patients. Also, noted in the Yeh et al study,51 MA had a delayed effect on weight gain with the statistically SUPPLEMENT
significant weight gain occurring 2 months following discontinuation of MA. Although the mechanism by which MA leads to weight gain is unknown, one postulated mechanism is that MA leads to a reduction in the inflammatory cytokines that have anorexia-promoting properties.54 In a concurrent study,55 Yeh et al compared cytokine levels in patients taking MA and placebo but did not find a statistically significant difference between groups at 12 weeks. However, there was a statistically significant negative correlation between changes in cytokine levels and changes in weight, eg, increased weight correlated with decreased levels of 2 of the 4 cytokines measured. Another issue involves whether providing an appetite stimulant without other supportive measures, including increased access to food or feeding assistance, is adequate. In a prospective, preliminary trial in the nursing home, Simmons et al56 found that MA improved oral food and fluid intake under optimal mealtime feeding assistance but not under usual nursing home care. For a subset of nursing home patients, MA can improve appetite and lead to weight gain. Further studies will need to elucidate which patients are most likely to respond and when in the course of weight loss MA should be initiated, especially given that weight gain may not occur for months. Other A variety of other agents have been investigated to stimulate appetite or increase weight. Pentoxifylline and thalidomide both decrease tumor necrosis factor-␣ and have been studied in HIV-infected patients with varying results.57 Testosterone replacement in older men has been shown to increase muscle mass.58 Patients with advanced lung cancer who were randomized to receive the anabolic agent nandrolone, in addition to combination chemotherapy, showed a trend for less severe weight loss.59 Although some studies suggested growth hormone may be beneficial in malnourished older persons,60,61 a subsequent trial in critically ill, malnourished patients found an increased rate of death in patients treated with growth hormone.62 Glucocorticoids have been used to improve appetite and mood in cancer cachexia but side effects often limit use to palliative care. In one study, ornithine oxoglutarine was shown to increase appetite and promote weight gain in older patients following acute illness.63 Psychotropic Medications Psychiatric conditions, such as depression, anxiety, and behavioral disturbances associated with dementia are prevalent in a nursing home population. Medication selection is often influenced by side effect profile, including effects on weight and appetite. Antidepressant Medication Many clinicians attribute weight gain to tricyclic antidepressant (TCA) therapy and weight loss to selective serotonin reuptake inhibitor (SSRI) therapy. However, there are few data to support these beliefs.64,65 In a retrospective chart review in a VA setting, Brymer and Winograd65 reported that 47% (7 of 15) of outpatients older than 75 years taking fluoxetine lost more than 5% of their initial body weight Aoyama et al. S69
compared with none (0 of 20) of those receiving TCAs. In a large retrospective cohort study using the MDS, Rigler et al66 found that SSRI use was associated with both weight gain and weight loss of marginal significance and that TCA use was not associated with clinically important weight gain. Additionally, the differences in mean weight changes between SSRIs, TCA, and other antidepressants were small and not clinically significant for most patients. Mirtazapine, an antidepressant with noradrenergic and serotonergic effects, has been characterized as a “1-stop” antidepressant because of its reported benefits on several depression-related symptoms including insomnia and weight loss. Fawcett and Barkin67 reviewed clinical trials of mirtazapine and reported a statistically significant increase in appetite and weight gain from pooled data in mirtazapine-treated patients over placebo. In a retrospective chart review of 50 nursing home patients treated with mirtazapine or sertraline for 4 months for major depression or dementia with depression, weight gain was similar in both.68 In contrast, 2 randomized, double-blind clinical trials69,70 showed mirtazapine to have positive effects on weight gain and improved depression scale scores. In an 8-week, comparative trial in 246 depressed elderly patients, 10.9% of patients on mirtazapine gained weight versus none on paroxetine, which was statistically significant.69 The mean body weight in the mirtazapine group increased approximately 1.7 kg during the study period. Additionally, 5 patients in the mirtazapine group experienced a greater than 7% gain from baseline in contrast to none in the paroxetine group. Halikas70 conducted a 6-week study comparing placebo, trazodone, and mirtazapine in 150 older adults with depression. Twenty-four percent of the mirtazapine group reported increased appetite as compared with 4% of placebo-treated group and 6% in the trazodone group. The group on mirtazapine showed a mean weight gain of 1.3 kg from baseline. Mirtazapine has been shown to improve appetite and contribute to a modest weight gain in older adults undergoing treatment for depression. It is uncertain whether mirtazapine will have a similar effect in nondepressed patients. Antipsychotic Medication Conventional antipsychotic medications have been associated with significant weight gain in adults.71 Atypical antipsychotics were developed to have less extrapyramidal side effects but have also been noted to contribute to weight gain in adult populations.72,73 Elderly patients, including those in nursing homes, are commonly prescribed antipsychotic medications.74 In a trial comparing varying doses of olanzapine versus placebo to manage behavior in patients with Alzheimer’s disease, no significant weight changes were seen.75Although atypical antipsychotics have been shown to increase weight in younger populations, it is uncertain whether they have a similar effect in an older population. SUMMARY AND CONCLUSION Undernutrition and weight loss are complex issues in the nursing home. With multiple medical, psychological, and social variables in the nursing home patient, health care providers should develop a mechanism to identify patients at risk for undernutrition and weight loss. Then, the resources of an interS70 Aoyama et al.
disciplinary team would ideally be implemented to determine an etiology for the weight loss. Specific measures should be taken to address the determined cause, for example antidepressants for depressed patients. Behavior interventions, such as ensuring adequate feeding assistance and encouraging socialization at meal times, are simple ways to improve the nutritional status of nursing home patients. Encouraging family members to bring in favorite foods; making available frequent, high-caloric snacks; and ordering oral nutritional supplements are several ways to potentially increase oral food and calorie intake. If anorexia is considered to be a significant factor in weight loss, a trial of an appetite stimulant, such as megestrol acetate, may be attempted. In depressed older patients, mirtazapine appears to have some weight gain benefits. Antipsychotics have been shown to increase weight in younger patients, but convincing data in older patients are not yet available. Although identifying and addressing the cause for weight loss is the initial step, various interventions are often employed concomitantly. Often, multiple, simultaneous interventions will be necessary, as no single intervention will be successful in all patients. Of note, when patients’ family members were queried about preferences to improve their relative’s oral food and fluid intake, they ranked the following interventions from most to least desirable: (1) improve quality of food; (2) improve quality and quantity of feeding assistance; (3) provide multiple small meals and snacks throughout the day; (4) place resident in preferred dining location; (5) provide an oral liquid nutritional supplement between meals; and (6) provide medication to stimulate appetite.76 Clearly, options exist to improve and maximize the nutritional health of nursing home patients, but more research is needed to explore the causes of weight loss in the very old, which may facilitate the development of specific, targeted interventions. REFERENCES 1. Sullivan DH, Morley JE, Johnson LE, et al. The GAIN (Geriatric Anorexia Nutrition) Registry: The impact of appetite and weight on mortality in a long-term care population. J Nutr Health Aging 2002;6: 275–281. 2. Blaum CS, Fries BE, Fiatarone MA. Factors associated with low body mass index and weight loss in nursing home residents. J Gerontol 1995: 50A:M162–M168. 3. Silver AJ, Morley JE, Strome LS, et al. Nutritional status in an academic nursing home. J Am Geriatr Soc 1988;36:487– 491. 4. Wallace JI, Schwartz RS, LaCroix, AZ, Uhlmann RF, Pearlman RA. Involuntary weight loss in older outpatients: Incidence and clinical significance. J Am Geriatr Soc 1995;43:329 –337. 5. Ryan C, Bryant, E, Eleazer P, et al. Unintentional weight loss in longterm care: Predictor of mortality in the elderly. South Med J 1995;88: 721–724. 6. Murden RA, Ainslie NK. Recent weight loss is related to short-term mortality in nursing homes. J Gen Intern Med 1994;9:648 – 650. 7. Chang JI, Katz PR, Ambrose P. Weight loss in nursing home patients: Prognostic implications. J Fam Pract 1990;30:671– 674. 8. Morley JE, Kraenzle D. Causes of weight loss in a community nursing home. J Am Geriatr Soc 1994;42:583–585. 9. Katz IR, Parmelee PA. Depression in elderly patients in residential care settings. In: Diagnosis and treatment of depression in late life: Results of the NIH Consensus Development Conference. Schneider LS, Reynolds CV III, editors. Washington, DC: American Psychiatric Press; 1994. p. 463– 490. 10. Fitten LJ, Morley JE, Gross PL, Petry SD, Coke KD. Depression. J Am Geriatr Soc 1989; 37:459 – 472. JAMDA – March 2006
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