Appetite-Enhancing Drugs

Definition

Appetite-enhancing drugs are a diverse group of medications given to prevent undesired weight loss in the elderly and in patients suffering from such diseases as AIDS and cancer, which often result in wasting of the body's muscle tissue as well as overall weight loss. The medical term for these drugs is orexigenic, which is derived from the Greek word for "appetite" or "desire." None of the orexigenic drugs in common use as of 2005, however, were originally formulated or prescribed as appetite stimulants; they range from antihistamines and antiemetics (drugs given to treat or prevent nausea and vomiting ) to antidepressants and synthetic hormones. The medications most often used in the early 2000s include mirtazapine (Remeron), a tetracyclic antidepressant; cyproheptadine (Periactin), an antihistamine; dronabinol (Marinol, THC), an antiemetic; nandrolone, oxymetholone, and oxandrolone (Anadrol-50, Durabolin, Hybolin, Oxandrin, and other brand nam! es), which are anabolic steroids related to the male sex hormone testosterone; and megestrol acetate (Megace), a synthetic derivative of the female sex hormone progesterone. In addition to these prescription drugs, fish oil (eicosapentaenoic acid or EPA) has been recommended as an alternative or complementary treatment for undesired weight loss.

Purpose

The reader should note the distinction between appetite and hunger in order to understand why a group of such different medications could be used to stimulate the desire for food. Hunger is defined as the body's basic physical need for food, whether in terms of calorie content or specific nutrients. Appetite, on the other hand, refers to the complex desires in humans for food and drink that are often conditioned or influenced by previous experiences or cultural factors as well as by a person's present health status. People may have an appetite for food in the absence of hunger; conversely, they may be hungry in the physical sense but have little or no appetite. Loss of appetite may lead to a type of malnutrition known as undernutrition, which is characterized by food intake that falls below a recommended daily allowance of calories or by the body's inability to make use of the nutrients in the food that is consumed.

People may become anorexic (lose their appetite for food) for a variety of physical, emotional, and social reasons:

• Sensory changes related to aging. Elderly persons often experience a partial loss of the senses of taste and smell, which means that they may not enjoy their meals as much as they did when they were younger. In addition, many elderly persons feel full after eating relatively small amounts of food. It is thought that this early feeling of fullness is caused by increased secretion of gastric hormones known as cholecystokinins.
• Gastrointestinal disorders. Patients with such disorders as Crohn's disease or gastric atonia (abnormally slow emptying of the stomach) may lose their appetite for food.
• Severe diseases that affect the entire body, particularly cancer and AIDS. Patients with these diseases may develop cachexia, a potentially life-threatening condition characterized by unintended weight loss and wasting of lean muscle tissue. Cachexia is often accompanied by loss of appetite.
• Medication side effects. In addition to the drugs used in cancer chemotherapy, such drugs as fluoxetine (Prozac), digoxin (Lanoxin), quinidine (Duraquin, Cardioquin), hydralazine (Alazine, Apresoline), certain antibiotics, and vitamin A may cause loss of appetite.
• Emotional stress. Many people do not feel like eating before examinations, job interviews, public speaking, artistic performances, athletic competitions, or similar stressful situations.
• Depression and other mood disorders. Loss of appetite is a common feature of depressive episodes as well as of major depressive disorder.
• Cultural factors. The types of food that people find appetizing are influenced by their respective cultures; for example, Westerners usually find the use of cats and dogs for food in China and Korea upsetting or disgusting because they regard these animals as domestic pets rather than dietary items. In addition, many people lose their appetite when they discover insects, hair, or other evidence of unsanitary conditions in their food, or when they find that a dish's ingredients violate the dietary laws of their religion.
• Social isolation. Research indicates that human appetite for food is stimulated by eating in the company of others. Loss of appetite in many elderly people is associated with living alone.
• Previous experience. People who have developed food poisoning after eating contaminated or improperly refrigerated salads, raw clams or oysters, or similar foods may develop a long-term distaste for the food that made them sick.

Given the complexity and variety of factors that influence the desire for food in humans, doctors often use such questionnaires as the Mini Nutritional Assessment or the Nutrition Screening Index before prescribing any appetite-enhancing drug. Many patients can be successfully treated by changes in the type or dosage of medications they are taking for other conditions, or by therapy directed at an underlying mood disorder or gastrointestinal disease. Others can be helped by changes in their living situations that allow them to share mealtimes with others or by assistance in preparing foods that they particularly enjoy. The American Academy of Home Care Physicians (AAHCP) noted in a report published in May 2004 that the use of orexigenic drugs in the elderly is "controversial and not generally FDA-approved."

Description

Orexigenic drugs used in the United States as of 2005 are classified as follows:

• Mirtazapine. Mirtazapine is a tetracyclic antidepressant that was approved by the Food and Drug Administration (FDA) in 1996 for the treatment of major depression. Although researchers do not fully understand why mirtazapine relieves mood disorders, they think that it increases the levels of noradrenaline and serotonin (chemicals that transmit nerve impulses across the gaps between cells) in the brain. Mirtazapine is most often prescribed as an appetite stimulant for patients who have been previously diagnosed with depression.
• Cyproheptadine. Cyproheptadine is an antihistamine given to relieve the symptoms of colds, nasal allergies, and hay fever. It is also prescribed to relieve the itching associated with insect bites and stings, poison ivy, and poison oak. It appears to be most effective in treating loss of appetite in children and adults diagnosed with cystic fibrosis.

• Dronabinol. Dronabinol is a synthetic version of tetrahydrocannabinol (THC), the mood-altering compound found in marijuana (Cannabis sativa ). Marijuana has been known as an appetite stimulant for centuries, having been recommended for that purpose by Ayurvedic practitioners and by the Arabic physician Al Badri, who first described its orexigenic properties in 1251. Dronabinol is most commonly used to treat the nausea and vomiting associated with AIDS and with cancer chemotherapy.
• Anabolic steroids. These drugs are given to older persons to increase muscle mass and strength, or to help patients recovering from severe illness or injury to regain lost weight.
• Megestrol acetate. Megestrol acetate was first approved by the FDA in 1976 for palliative treatment of metastatic breast or endometrial cancer. It received additional approval in 1993 for the treatment of anorexia or unexplained weight loss in patients with AIDS. Researchers do not fully understand how the drug prevents the growth of cancer cells or how it stimulates appetite.
• Fish oil. Fish oil is recommended by some practitioners as a nutritional supplement for weight loss caused by cancer or AIDS. It is thought that the omega-3 fatty acids in fish oil help to reduce the inflammation associated with some forms of cancer therapy as well as helping patients regain lost weight. Although some studies question the effectiveness of fish oil as a complementary treatment for undesired weight loss, the National Center for Complementary and Alternative Medicine (NCCAM) is recruiting patients as of April 2005 for a clinical trial of fish oil as a dietary supplement to maintain weight in patients with pancreatic cancer. The study will be completed in September 2007.

KEY TERMS

Anabolic steroids— A group of drugs derived from the male sex hormone testosterone, most commonly prescribed to promote growth or to help the body repair tissues weakened by severe illness or aging. Some anabolic steroids are given as appetite stimulants.

Anorexia— Loss of appetite for food.

Antiemetic— A type of medication given to relieve or prevent nausea and vomiting. Some appetite-enhancing drugs are also used as antiemetics.

Appetite— The natural instinctive desire for food. It should be distinguished from hunger, which is the body's craving or need for food (either calories or specific nutrients).

Cachexia— A condition of general ill health, malnutrition, undesired weight loss, and physical weakness, often associated with cancer.

Off-label— Referring to the use of a drug for a condition or disorder not listed in the official FDA labeling.

Orexigenic— The medical term for drugs that increase or stimulate the appetite.

Palliative— Referring to drugs or other therapies intended to relieve the symptoms of a disease rather than to cure it.

Undernutrition— A type of malnutrition caused by inadequate food intake or the body's inability to make use of needed nutrients.

Recommended dosage

Recommended dosages for orexigenic drugs are as follows:

• Mirtazapine. Mirtazapine is available in 15- and 30-mg tablets or disintegrating tablets. The usual starting dose is 15 mg once daily, usually at bedtime. The drug can be taken with or without food, as the patient prefers.
• Cyproheptadine. Cyproheptadine is taken by mouth, either as tablets or in liquid form. Adults are usually given 4 mg three or four times per day. Children between 2 and 6 years of age are usually given 12 mg per day in 3-4 divided doses while older children are given 16 mg per day in divided doses.
• Dronabinol. As an appetite stimulant, dronabinol is given as a 2.5-mg capsule twice a day, before lunch and dinner. Some AIDS patients may be given as much as 10 mg per day.
• Anabolic steroids. Oxandrolone and oxymetholone are available in the United States and Canada as tablets, while nandrolone is given by injection. To build up body tissues after injury or serious illness, the adult dosage of oxandrolone is a 2.5-mg tablet taken by mouth two to four times daily for a period of four weeks, although the total daily dosage may be raised as high as 20 mg. To treat anemia, oxymetholone is prescribed according to the patient's body weight, usually 0.45-2.3 mg per pound of body weight per day in adults and children. Nandrolone is given by injection every three to four weeks for a period of 12 weeks. The usual dosage for women and girls over 14 is 50-100 mg; for men and boys over 14, 50-200 mg; for children between the ages of 2 and 13, 15-50 mg.
• Megestrol acetate. Megestrol acetate is given as a liquid suspension in 200-mg doses every 6 hours.
• Fish oil. A recommended dose for cancer-induced weight loss is 12 g daily, taken by mouth. Fish oil is available in capsules as well as liquid forms.

Precautions

Precautions for orexigenic drugs are as follows:

• Mirtazapine. In January 2005 the FDA required labeling changes for mirtazapine to warn of the increased risk of suicide or self-harm in children or adolescents taking this drug. Mirtazapine should not be given to children below 18 years of age, and should be used with caution in pregnant or lactating women. Patients taking mirtazapine should not stop taking it without telling their doctor; it should not be discontinued abruptly but taken in progressively smaller doses over a period of time. This precaution is particularly important in patients who have been taking the drug for a long time.
• Cyproheptadine. This drug should not be given to patients who suffer acute asthma attacks or are hypersensitive to antihistamines. It should not be given to patients who have taken phenelzine (Nardil), tranylcypromine (Parnate), or other MAO inhibitors within the last two weeks. Cyproheptadine should be used cautiously in the elderly and in patients with glaucoma, high blood pressure, or cardiovascular disease.
• Dronabinol. Patients taking dronabinol should be closely supervised by their doctor, as the drug may cause unpredictable changes in blood pressure and heart rate. In addition, it may make certain mental disorders worse. It also has a high potential for abuse; for this reason, it should be used cautiously in patients with a history of alcohol or drug abuse. Dronabinol should not be used by nursing mothers because it passes into breast milk. It should be used with great caution in children or patients diagnosed with severe mental illness because of its effects on the mind. Patients taking dronabinol should notify their dentist or surgeon before any procedure requiring local or general anesthesia, as the drug may intensify the effects of the anesthetic. In addition, these patients should not drive a car or operate dangerous machinery until they know whether dronabinol makes them dizzy, drowsy, or uncoordinated.
• Anabolic steroids. Patients taking these drugs must follow a diet high in protein and calories in order to benefit from the medications, and should be carefully supervised by their doctor because of possible side effects. Children or teenagers taking these drugs should have x-rays every six months to make sure they are growing normally, as anabolic steroids can interfere with growth. Patients with diabetes should check their blood sugar levels with extra care, as these drugs may cause rapid changes in blood sugar levels.
• Megestrol acetate. This drug should not be used by pregnant or lactating women, or by women planning to become pregnant. Women of childbearing age who are taking megestrol should use a reliable form of contraception.
• Fish oil. Fish oil is not a prescription drug; however, patients who choose to take cod liver oil as their fish oil supplement should make sure that they are not getting more than the safe maximum daily allowances of vitamins A and D. These vitamins tend to build up in the body and may reach toxic levels. The maximum safe daily level of vitamin A for adults is 3000 micrograms (mcg).

Side effects

Side effects reported for orexigenic drugs are as follows:

• Mirtazapine. Mirtazapine may cause mood changes, including worsening depression or thoughts of suicide. It may also cause panic attacks, irritability, difficulty with impulse control, abnormal levels of excitement, or difficulty sleeping. Physical side effects may include sleepiness, dry mouth, constipation, nausea and vomiting, flu-like symptoms, chest pain, and rapid heartbeat. Patients who have any of these side effects should consult their doctor at once.
• Cyproheptadine. Side effects include drowsiness, fatigue, dry mouth, skin rash, chest congestion, headache, diarrhea, nausea and vomiting, difficulty urinating, and blurred vision. Patients who experience urinary or vision problems should consult their doctor at once.
• Dronabinol. Dronabinol may cause a variety of changes in mental status, including delirium, confusion, hallucinations, memory loss, delusions, euphoria (false sense of well-being), nervousness or anxiety. Because of the possibility of severe mental side effects, anyone who has taken an overdose of dronabinol needs immediate emergency medical help. The drug may also cause clumsiness or lightheadedness, dry mouth, fatigue, headache, sweating, facial flushing, diarrhea or constipation, muscle pains, high blood pressure, seizures, problems in urinating, red eyes, or vomiting.
• Anabolic steroids. These drugs have been reported to cause a rare form of liver disease; patients who notice yellowing of the eyes or skin, or black, tarry stools, sore throat and fever, vomiting of blood, or purplish or reddish spots on the body should contact their doctor at once. Other side effects include feeling chilly, diarrhea, muscle cramps, unusual increase or decrease in sexual desire, acne or oily skin, bone pain, nausea, or vomiting. Women may notice deepening of the voice, hair loss, unnatural hair growth (hirsutism ), or irregular menstrual periods. Adult males may notice enlargement of the breasts (gynecomastia ), frequent need to urinate, or frequent erections. Elderly males may have difficulty urinating.
• Megestrol acetate. Side effects of megestrol acetate include swelling of the hands, feet, or lower legs; headaches; sore breasts; or decreased sexual desire. Men taking this drug may become impotent. Women may notice vaginal bleeding or abdominal pain.
• Fish oil. Some people taking fish oil as a dietary supplement experience an increased tendency to burp followed by a fishy taste in the mouth.

Interactions

Most orexigenic drugs interact with a number of other medications:

• Mirtazapine. Mirtazapine may cause high blood pressure or abnormally high body temperature if taken together with MAO inhibitors (furazolidone, phenelzine, procarbazine, selegiline, or tranylcypromine). It intensifies the sedating (sleep-inducing) effects of alcohol, benzodiazepine tranquilizers, antihistamines, tricyclic antidepressants, narcotic pain relievers, and some medications given for high blood pressure.
• Cyproheptadine. Cyproheptadine intensifies and prolongs the effects of other antihistamines, alcohol, barbiturates, narcotic pain relievers, benzodiazepine tranquilizers, and antidepressant medications.
• Dronabinol. Dronabinol intensifies the effects of alcohol and other medications that act as central nervous system depressants. These groups of drugs include barbiturates, benzodiazepine tranquilizers, tetracyclic and tricyclic antidepressants, narcotic pain relievers, antiseizure medications, antihistamines, muscle relaxants, and anesthetics, including dental anesthetics.
• Anabolic steroids. Anabolic steroids may intensify the effects of blood thinners (aspirin, coumadin, warfarin). They may increase the risk of liver damage in patients who are taking phenothiazines, valproic acid, oral contraceptives containing estrogen, gold salts, methotrexate, carbamazepine, amiodarone, mercaptopurine, phenytoin, plicamycin, disulfiram, daunorubicin, chloroquine, methyldopa, or naltrexone.
• Megestrol acetate. No significant interactions with other drugs have been reported. Patients taking megestrol acetate should, however, notify their physician of all other drugs and dietary supplements (including herbal preparations) that they use on a regular basis, as dosage adjustments are sometimes needed.
• Fish oil. Fish oil has been reported to intensify the effects of such blood-thinning medications as coumadin and warfarin. Persons who take these drugs and wish to use fish oil as a dietary supplement should consult their doctor first.

Resources

BOOKS

"Malnutrition." Section 1, Chapter 2 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

"Protein-Energy Undernutrition." Section 8, Chapter 61 in The Merck Manual of Geriatrics, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Wilson, Billie A., Margaret T. Shannon, and Carolyn L. Stang. Nurses Drug Guide 2000, Stamford, CT: Appleton & Lange, 2000.

PERIODICALS

Anttila, S. A., and E. V. Leinonen. "A Review of the Pharmacological and Clinical Profile of Mirtazapine." CNS Drug Reviews 7 (Fall 2001): 249-264.

Grinspoon, S., and K. Mulligan. "Weight Loss and Wasting in Patients Infected with Human Immunodeficiency Virus." Clinical Infectious Diseases 36 (April 1, 2003) (Supplement 2): S69-S78.

Holder, H. "Nursing Management of Nutrition in Cancer and Palliative Care." British Journal of Nursing 12 (June 12-25, 2003): 667-674.

Homnick, D. N., B. D. Homnick, A. J. Reeves, et al. "Cyproheptadine Is an Effective Appetite Stimulant in Cystic Fibrosis." Pediatric Pulmonology 38 (August 2004): 129-134.

Jatoi, A., K. Rowland, C. L. Loprinzi, et al. "An Eicosapentaenoic Acid Supplement Versus Megestrol Acetate Versus Both for Patients with Cancer-Associated Wasting: A North Central Cancer Treatment Group and National Cancer Institute of Canada Collaborative Project." Journal of Clinical Oncology 22 (June 15, 2004): 2469-2476.

Jatoi, A., H. E. Windschitl, C. L. Loprinzi, et al. "Dronabinol Versus Megestrol Acetate Versus Combination Therapy for Cancer-Associated Anorexia: A North Central Cancer Treatment Group Study." Journal of Clinical Oncology 20 (January 15, 2002): 567-573.

Morley, J. E. "Orexigenic and Anabolic Agents." Clinics in Geriatric Medicine 18 (November 2002): 853-866.

Vickers, S. P., and G. A. Kennett. "Cannabinoids and the Regulation of Ingestive Behaviour." Current Drug Targets 6 (March 2005): 215-223.

ORGANIZATIONS

American Academy of Home Care Physicians (AAHCP). P. O. Box 1037, Edgewood, MD 21040-0337. (410) 676-7966. Fax: (410) 676-7980. 〈http://www.aahcp.org〉.

American Psychiatric Association (APA). 1000 Wilson Boulevard, Suite 1825, Arlington, VA 22209-3901. (800) 368-5777 or (703) 907-7322. Fax: (703) 907-1091. 〈http://www.psych.org〉.

American Society of Health-System Pharmacists (ASHP). 7272 Wisconsin Avenue, Bethesda, MD 20814. (301) 657-3000. 〈www.ashp.org〉.

National Cancer Institute (NCI). NCI Public Inquiries Office, Suite 3036A, 6116 Executive Boulevard, MSC8332, Bethesda, MD 20892-8322. (800) 4-CANCER or (800) 332-8615 (TTY). 〈www.nci.nih.gov〉.

United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA. 〈www.fda.gov〉.

OTHER

Food and Drug Administration (FDA) MedWatch, January 2005. "Summary View: Safety Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)—January 2005." 〈http://www.fda.gov/medwatch/SAFETY/2005/jan05_quickview.htm〉.

Morley, John E., David R. Thomas, and Margaret-Mary G. Wilson. "Appetite and Orexigenic Drugs." St. Louis, MO: Council for Nutrition, Clinical Strategies in LongTerm Care, 2001.

National Center for Complementary and Alternative Medicine (NCCAM). "Clinical Trial: A Fish Oil Supplement to Maintain Body Weight in Pancreatic Cancer Patients." 〈http://clinicaltrials.gov/show/NCT00094562〉.

Taler, George, MD, and Christine Ritchie, MD. "Unintended Weight Loss Guidelines.". Edgewood, MD: American Academy of Home Care Physicians, 2004.