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Appetite Stimulants:

Appetite Stimulants:. Effects in Elderly. By: Nicole Parello and Jeanette Kimszal. Appetite Stimulants: Overview. May help promote appetite and weight gain in elderly with unintentional weight loss or poor P.O. intake Drugs should not be considered as first-line treatment

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Appetite Stimulants:

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  1. Appetite Stimulants: Effects in Elderly By: Nicole Parello and Jeanette Kimszal

  2. Appetite Stimulants: Overview May help promote appetite and weight gain in elderly with unintentional weight loss or poor P.O. intake Drugs should not be considered as first-line treatment Even if successful in inducing weight gain, long-term effects on quality of life are unknown The following appetite stimulants have been researched in literature Dronabionol (Marinol) Mirtazapine (Remeron) Megestrol Acetate (Megace) Metoclopraminde (Reglan) Cyproheptadine (Periactin) Anabolic Steroids (Oxandrolone; Oxandrin) Ghrelin Recombinant Human Growth Hormone (Serostim) Testosterone

  3. Dronabinol Drug name: Marinol What it is: A tetrahydrocannabinol Use: Weight gain in cancer-related anorexia patients Side Effects: Lightheadedness Sleepiness Blurred vision Can’t think clearly Dizziness Sedation Fatigue Hallucinations

  4. Dronabinol Research Useful in anorexia, weight gain, & behavior problems in patients with advanced Alzheimer's disease according to limited non-randomized trial well-tolerated & showed trend toward weight gain in small 12 week retrospective observational study (Agarwal, 2012) Trend toward weight gain among 28 long-term care patients in retrospective uncontrolled 12 week observational study (Stajkovic et al., 2011) 2.5 mg 1x/week, then 2.5 mg 2x daily 30 min before lunch and dinner Few major outcomes of anorexia & weight loss patients treated 12+ weeks in retrospective observational pilot study (Rudolph, 2010) 53.5% had minimal weight gain 11 subjects lost weight on Dronabinol and were younger in age then those who gained weight (70.9 versus 90.8 years) and the outcomes were not very significant No controlled trials done on Dronabinol (Stajkovic et al., 2011) Increase desire to eat, improves taste, reduces anxiety, improves sleep, good for hospice care (Morley, 2012) Triggers brain to tell stomach to eat more, eases stomach and throwing up (Up-to-Date, 2013) Limit use in older adult populations due to side effects (Agarwal, 2012) Avoid use with not well defined cognitive deficits (Hoffman, 2002) Improve appetite in AIDS patients; little research on older adults (Agarwal, 2012)

  5. Mirtazapine • Drug Name: Remeron • What it is: A serotonergic norepinephrine uptake inhibitor used to treat depression in older adults • Use: • Appetite stimulant for cachexia and treats underlying depression in older adults • Side Effects: • Sedation • Dry mouth • Constipation • Fatigue • Weight gain • Dizziness • Other studies show causes hepatotoxicity, bone marrow suppression, restless legs syndrome, arthralgia, and coagulopathy

  6. Weight gain in 12% of patients, inhibits receptors of serotonin and stimulates appetite (Fox et al., 2009) Treatment of choice for people with depression & weight loss in older adults; no studies on use as an appetite stimulant in a long term care setting; Use for unintended weight loss not recommended in the absence of depression (Rudolph, 2010) The treatment of depression likely had a greater effect on weight gain than the specific agent used when compared with other nontricyclic antidepressants in two groups of depressed older adults with similar weight gain (Agarwal, 2012) (Agarwal, 2012) 1.1 pounds weight increase in 4 weeks & 1.32 pounds in 12 weeks; outcome was not found to be statistically significant (Rudolph 2010) Mean dosage 15 mg/day; recommended initial dose in elderly is 7.5 mg/day with a slow titration (every 2-4 wks) to effect; due to sedative properties, this drug should be titrated with caution especially in patients with a high risk for falls (Fox et al., 2009) Not initially recommended for patients with swallowing difficulties (Fox et al., 2009) Inexpensive substitution for Megace (Fox et all, 2009) Not recommended to have patients take this drug to promote weight gain while continuing on another depression medication (Fox et al., 2009) Mirtazapine Research

  7. Megestrol Acetate Drug Name: Megace What it is: A progestational agent Use: Weight gain in Anorexia, AIDS, Cachexia, and Cancer patients Side Effects: Edema Constipation & delirium Diarrhea Flatulence Rash Hypertension Fluid retention Glucose intolerance Nausea Insomnia • Gastrointestinal upset • Impotence • Adrenal insufficiency • Thromboembolic events (thrombosis) & possibly death in elderly (UptoDate, Beers) • Confusion occurred as major side effect (Rudolph, 2010)

  8. Megestrol Acetate Research Doses <320 mg may be effective for stimulating weight gain in frail elderly patients, needs to be tested in randomized controlled trials (Hoffman, 2002) Weight gain not significant (<4 lbs) until after 3 months (800 mg/d) (Agarwal, 2012) Long term care populations used as an appetite stimulant; 9 studies with mixed outcomes(Rudolph, 2010) Fat gain main component to increased body weight; this drug does not restore lean muscle mass in older adults (Rudolph, 2012) Safe & efficient to improve nursing home malnutrition but confounding factors of other interventions and supplements need to be studied (Rudolph, 2010) Use with caution in older patients with unintentional weight loss due to evidence of benefit and significant side effects (Agarwal, 2012) Causes weight gain in patients with anorexia and cachexia (Agarwal, 2012)

  9. Metoclopramide Drug Name: Reglan What it is: Prokinetic agent Use: Relieves nausea-induced anorexia (Hoffman, 2002) Side Effects: Dystonia & Parkinsonian symptoms in elderly Many drug interactions such as B12, D3, Lipitor, Fish oils, Aspirin, Crestor Can cause GI obstruction, perforation or hemorrhage Causes GI obstruction, perforation or hemorrhage; pheochromocytoma; history of seizures or concomitant use of other agents likely to increase movement disorder reactions May increase risk of seizures and movement disorders (extrapyramidal reactions)

  10. Metoclopramide Research Treatment > 12 weeks is not recommended (Uptodate, 2013) The initial dosage of metocloproadmide in a 19 yr old girl with anorexia nervosa and delayed gastric emptying, showed no significant change in body weight until an increase in dose resulted in a 20% increase in the patient’s body weight over a 2-month period (Sansone et. al, 2003) Geriatrics should start at low end of dosage 10 mg/dose up to 4x/day (Uptodate, 2013)

  11. Cyproheptadine Drug name: Periactin What it is: Antihistaminic and serotonin-blocking drug Use: Weight gain in children with anorexia nervosa & cancer Elderly in nursing homes Side Effects: Blurred vision Dry mouth Urinary retention Constipation Tachycardia and delirium in older patients

  12. Cyproheptadine Research Decrease weight loss rate in 65 yrs, no weight gain (Hoffman, 2002) Drowsiness and dizziness in the elderly population which is problematic elderly (Hoffman, 2002) Some benefits of 4 mg qd or bid without reversing antidepressant efficacy (Ernst, 2012) Increase appetite in adults without reducing weight loss (AND, Kardinal, 1990) Weight gain in pediatric cancer patients (AND, Couluris, 2008) Avoid use of this potent anticholinergic agent due to increased risk of confusion, clearance decreases in patients of advanced age (Rudolph, 2010) Weight gain in pediatric anorexia nervosa & Cancer patients (Rudolph, 2012) Limit use in long-term care of older patients since no appetite stimulant studies have been developed (Rudolph, 2010)

  13. Anabolic Steroids Drug Name: Oxandrolone (Oxandrin), Ornithine What it is: Synthetic anabolic steroids Use: Treats wasting in AIDS & Cachexia in Cancer Side Effects Carpal tunnel syndrome Headache Arthralgias Myalgias, & gynecomastia Risk of prostate hyperplasia, fluid retention, and transaminase elevations

  14. Anabolic Steroids Research Wound healing improvement: weight loss & non-healing chronic wounds (Rudolph, 2010) Weight loss associated COPD patients improved appetite & increased weight gain (Rudolph, 2010) Studied to improve sarcopenia & frailty in older patients (Agarwal, 2012) Systematic review found that the risk of exogenous growth hormone outweigh potential benefits (Agarwal, 2012) No studies done in nursing home populations (Rudolph, 2010) and not test on elderly (Argarwal, 2012) Only drug approved by the FDA for the treatment of cachexia (Rudolph, 2010) Costly intervention (Hoffman, 2002) Risks with growth hormones (Agarwal, 2012)

  15. Ghrelin • Drug Name: None • What it is: Growth hormone produced from the fundus of the stomach increases food intake by stimulating nitric oxide in the hypothalamus • Use: Appetite stimulant in oncology patients and older adults • Side Effects: None noted

  16. Ghrelin Research Stimulates appetite and induces a positive energy balance that can lead to weight gain (uptodate) Implicated in regulating mealtime hunger and meal initiation (uptodate) Plays role in neurohormonal regulation of food intake and energy homeostasis (uptodate) An endogenous ligand for growth hormone secretagogue receptor, holds promise for the future, with preliminary studies demonstrating benefit in oncology patients and older adults; however long-term functional studies need to be completed before recommendations can be made (Agarwal, 2012) Limited research and few studies done on stimulant (Medication Guide, 2013)

  17. Recombinant Human Growth Hormone Drug Name: Serostim What it is: Anabolic Growth Hormone Use: Increase lean body mass in HIV patients with wasting or cachexia Side Effects: Carpal Tunnel Syndrome Headache Arthralgia Myalgias Gynecomastia Edema Arthralgia Impaired fasting glucose

  18. Recombinant Human Growth Hormone Research Studied as a way to improve sarcopenia and frailty in older patients (Agarwal, 2012) Increase in weight & lean muscle mass w/ decrease in body fat after 12 weeks among randomized double-blind placebo controlled study of 178 HIV-infected patients treated with 0.1 mg/kg of growth hormones (avg 6mg/d) (Schambelan et. al, 1996) Dosing caution with some patients ≥65 years sensitive treatment & prone to adverse effects (uptodate) Risks may out weight potential benefits (Agarwal, 2012) Expensive intervention Costly (Hoffman, 2002) Drug may be inappropriate for geriatric patents (BEERS); also avoid use in elderly as hormone replacement after pituitary gland removal (BEERS)

  19. Testosterone • Drug name: None • What it is: A steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates • Use: Treat cachexia and weight loss in HIV Patients • Side Effects: • Higher hematocrit • Leg edema • Prostate events (exacerbation of prostate cancer) • Lower HDL levels • Possible metabolic syndrome in men

  20. Testosterone Research • Supplementation increases skeletal muscle mass and strength; especially in older men (Agarwal, 2012) Weight and lean muscle mass increase but with unknown clinically meaningful changes in muscle function and disease outcome in HIV infected men (Yeh, 2007) • Studies in healthy older men have not demonstrated improvement in functional statue, physical function, or cognitive function (Agarwal, 2012) • Small study in undernourished community-dwelling older men and women did not find that combined treatment with oral testosterone undecanoate and oral nutritional supplement decreased hospital admission rates over one years, larger trials needed to confirm findings (Agarwal, 2012) • Selective androgen-receptor modulators that are preferentially anabolic and that spare the prostate hold promise as anabolic therapies (Yeh, 2007) • Due to insufficient psychological safety and efficacy evidence, use in elderly hypogonadal men (and to maintain the physiological circadian rhythm of serum testosterone levels) is not warranted (Yeh, 2007)

  21. Stimulants Currently on Formulary: Appetite Stimulants: Cypropheptadine (Periactin) Megace (Megestrol Acetate) Anabolic Steroids Mirtazpine (Remeron) Metoclopramide (Reglan)

  22. Recommendation • Limited Appetite stimulant research in long term care (Agarwal, 2012) • No evidence to support the use of Cyproheptadine (Periactin), Anabolic Steroids (Oxandolone), Metoclopramide (Reglan), or Mirtzapine (Remeron) as an appetite stimulant for treating unintentional weight in long term care (Rudolph, 2010) • Limited evidence suggests Dronabinol (Marinol) may be of benefit but not for more than 12 weeks (Rudolph, 2010); no control studies were done on Dronabinol (Marinol) so should not be recommended (Uptodat, 2013) • Some evidence shows Megestrol (Megace) may be of benefit; however its use is not without risks and has not been studied for long term periods of time (greater than 6 months) (Agarwal, 2013); Fat gain is main component in increase of body weight; may be inappropriate for geriatric patients (Rudolph, 2010)

  23. Recommendation Continued • Mirtazapine (Remeron) can be recommended for use with patients who have depression but not already taking other medications for depression Rudolph, 2010) • Metoclopramide (Reglan) should not be used until further scientific testing shows the benefits of this drug; do not take for longer then 12 weeks (Uptodate, 2013) • Cyproheptadine (Periactin) has mostly been studied in pediatrics; elderly should avoid use of this drug due to increased risk of confusion (Rudolph, 2012) • Risks of Recombinant Human Growth Hormones (Serostim) outweigh the benefits, this drug should not be used until further research on the elderly has been done (Agarwal, 2012) • Ghrelin may work as a future appetite stimulant; however, more investigation needs to go into this drug (Agarwal, 2012) • Testosterone should not be used in elderly patients due to the negative side affects (Agarwal, 2012)

  24. Sources: Agarwal, Kathryn MD. Failure to Thrive in elderly adults: Management. November 28, 2012. Uptodate.com. Baracos, Bowling, Bruera, Denmark-Wahnefried, Fabbro, & Hopkinson, 2010, “Nausea and Vomiting in Advanced Cancer,” Nutrition and the Cancer Patient, Oxford University Press: New York Couluris, Marisa; Jennifer L.R.Mayer, David R. Freyer, Eric Sandler, Ping Xu, Jeffrey P. Krischer. “The effect of cyproheptadine hydrochloride (Periactin) and megestrol acetate 9Megace) on weight in children with cancer/treatment-related cachexia.” Journal Pediatric Hematol Oncolo. 2008. November; 30 (11): 791-797. Ernst, Carrie L. Managing Side Effects of Psychotropic Medications. American Psychiatric Association. 2012. Fox, Carol B. Pharm.D.; Angela K. Treadway, Pharm.D., Amie T. Blaszczyk, Pharm.D., and Rebecca B. Sleeper, Pharm.D. Megestrol Acetate and Mirtazapine for the Treatment of Unplanned Weight Loss in the Elderly. Reviews of Therapeutics. Volume 29, Number 4, 2009. Healthinaging.org. AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. THE AGS FOUNDATION FOR HEALTH IN AGING. 2012. Homnick, Douglas N; John H. Marks, Karyl L. Hare, Sally K. Bonnema. “Long-term trial of cyproheptadine as an appetite stimulant in cystic fibrosis.” Pedicatric Pulmonology. Volume 40, Issue 3, p 251-256. September 2005. Huffman, Grace Brooke M.D.; Brooke Grove Foundation, Sandy Spring, Maryland. Evaluating and Treating Unintentional Weight Loss in the Elderly. American Family Physician. Volume 65, Number 4. February 15, 2002.

  25. Sources Cont’d: • Inui, Akio. Cancer Anorexia-Cachexia Syndrome: Current Issues in Research and Management. A Cancer Journal for Clinicians. CA; March/April 2002; 52: 72-91. (p.82-83). • Managing weight loss and fatigue in advanced illness. January 18, 2012. U.S. National Library of Medicine, PubMed Health. Cochrane Library. • Medication Guide. “Cancer Cachexia Appetite Stimulants (Orexigenic Medications).” March 15, 2013. • Morley, J.E. Anorexia of Aging: A True Geriatric Syndrome. The Journal of Nutrition, Health & Aging. Volume 16, November 5, 2012. • Rudolph, D.M. Appetite Stimulants in Long Term Care; A Literature Review. The Internet Journal of Advanced Nursing Practice. 2010 Volume 11 Number 1. DOI: 10.5580/186d. • Schambelan, Morris; Kathleen Mulligan, Carl Grunfeld, Eric S. Daar, Anthony Lamarca, Donald P. Kotler, Jack Wang, Samuel A. Bozzette, James B. Breitmeyer. “Recombinant Human Growth Hormone in Patients with HIV-Associated Wasting: A Randomized, Placebo-Controlled Trial.” Annals of Internal Medicine. 1 December 1996, Vol 125, No. 11. • Stajkovic, Svetlana; Elizabeth M. Aitken, Jayna Holroyd-Leduc. Unintentional weight loss in older adults. CMAJ, March 8 2011, 183 (4). • UpToDate.com. 2013. • Yeh, Shing-Shing MD, PhD, Sherri Lovitt, MD, and Michael W. Schuster, MDCachexia: Evidence and Safety in Perspective, 2007 from http://cmda.us/Articles/PDF/Geriatric%20Cachexia.pdf

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