03.21.2024

Addressing Loss of Appetite at End-of-Life

Patient case

DT is a 67 y/o male with a primary diagnosis of lung cancer that has metastasized to the brain and liver. He has a past medical history of diabetes and insomnia. Recently, the physician prescribed an opioid regimen to help manage DT’s uncontrolled pain.

Current medications:

  • Morphine ER (Kadian®) 20mg; one capsule by mouth daily for pain
  • Morphine IR 15mg; one-half tablet by mouth 4 times daily as needed for pain (currently using two doses per day)
  • Dexamethasone 4mg; 2 tablets by mouth twice daily for cerebral edema
  • Metformin 850mg; one tablet by mouth daily for blood sugars
  • Albuterol 90mcg inhaler; two inhalations every 4 hours as needed for shortness of breath
  • Haloperidol 2mg/mL oral solution; 0.5ml (1 mg) by mouth every four hours as needed for nausea and vomiting
  • Melatonin 1mg; one tablet by mouth at bedtime for sleep
  • Senna-docusate sodium 8.6mg-100mg; one tablet by mouth at bedtime for constipation

DT reports that his pain is well-managed but that the morphine causes an unacceptable level of daytime sleepiness while his longstanding insomnia is still an issue. Although his condition is stable, the family is concerned since he is hardly eating and is losing weight. They also report some signs of depression.

Understanding Appetite Loss in a Palliative Care Context

Patients with life-limiting illnesses often experience loss of appetite. While clinicians may consider this a normal part of the dying process, a recent study of more than 100,000 patients found that more than half (58%) reported some degree of distress about appetite at least once during the last sixty days of life.1 Clearly, lack of desire for food can be an issue for many patients.

Common diagnoses in end-of-life care as well as aging itself can limit appetite. Cancer, chronic obstructive pulmonary disease (COPD), Parkinson’s disease, Alzheimer’s disease, heart failure, depression and liver and kidney failure are all associated with a risk of decreased appetite, oral intake and weight loss. Physiologic changes that occur with aging such as hormonal changes, pain, changes to the senses (smell, taste, vision), and changes to the digestive system can impair appetite. A condition coined “anorexia of aging” was described in 1988. It is estimated that between 15% to 30% of older people experience anorexia of aging.2

Patients and caregivers may need education/reassurance that appetite and weight loss are part of the natural progression of the disease. Additionally, it’s important to educate caregivers that forced nutrition can cause aspiration, indigestion, and nausea, which may decrease the patient’s quality of life.

Non-Medication Causes and Risk Factors for Decreased Appetite and Weight Loss2
Acute illness
Anxiety
Bowel obstruction
Chronic nausea/vomiting
Cognitive impairment
Constipation
Dehydration
Delayed gastric emptying
Depression
Fatigue
Infection
Poor dentition
Reduced saliva production (which could be a side effect of medications)
Repeated paracentesis
Tumor mass causing early satiety
Uncontrolled pain

Multiple Approaches Improving Appetite at End-of-Life

Addressing any nausea or constipation the patient may be experiencing may improve appetite. This may require adding medications to manage those symptoms or adjusting medications which can cause them. There are hundreds of medications that can decrease appetite through gastrointestinal discomfort. Some medications are listed below:

Classes of Medications That Decrease Appetite Specific Medication Examples
Antiretroviral medication lamivudine, zidovudine
Cancer chemotherapy multiple
Radiation therapy multiple
Dementia medications donepezil, galantamine, rivastigmine
Quinolone antibiotics levofloxacin, ciprofloxacin
Macrolide antibiotics erythromycin, azithromycin
Other antibiotics ampicillin, tetracycline, metronidazole
Antifungals fluconazole, terbinafine
Anti-inflammatories celecoxib, ibuprofen
Opioid analgesics morphine, oxycodone, hydrocodone
Some antidepressants amitriptyline, nortriptyline, duloxetine
Stimulants methylphenidate, modafinil
Cardiac medications hydralazine, atorvastatin, amiloride, amiodarone, propafenone, dronedarone
Gout medications allopurinol, colchicine
Diabetes medication metformin, dulaglutide, semaglutide
Parkinson’s medications pramipexole, ropinirole, selegiline
Antipsychotics aripiprazole, risperidone
Mood stabilizers lithium
Seizure medications divalproex, valproic acid, levetiracetam

Regardless of cause, non-pharmacologic treatment may be preferred, as symptoms may not be reversible. Guidance on non-pharmacologic interventions include the following from the Hospice Foundation of America:3

  • Offer a variety of foods
  • Talk to your loved one about what they think would taste good and let them know it’s acceptable to not have a full meal
  • Offer small portions and do not force the patient to eat
  • Keep the mouth moist by offering water or other drinks and reminding the patient to drink. Applying sponges dipped in the patient’s favorite liquid can also be helpful.
  • If the patient was previously on a restricted diet, ask the hospice prescriber if these restrictions are still necessary

The use of medications to stimulate appetite lacks strong evidence. In fact, the 2020 Guideline on Management of Cancer Cachexia (a syndrome of progressive weight loss, muscle atrophy, fatigue and weakness) states “evidence remains insufficient to strongly endorse any pharmacologic agent to improve cancer cachexia outcomes.”3

Despite this, clinicians may turn to agents such as corticosteroids, progesterone analogs, and others that have limited evidence for improving appetite. The most commonly used agents are summarized below:

Medication Notes Adverse Effects
Corticosteroids Dexamethasone

(Decadron®)

4-8mg/day

 

 

Improves appetite

Weight gain: little if any

May help patients with life expectancy < 6 weeks (appetite stimulation effects lessen over time with continued use)

Decrease nausea, improve “sense of well-being”

Recommended as first line therapy when treatment for day to weeks is anticipated

CNS effects (dizziness, euphoria, impaired cognition)

Edema, hyperglycemia, immunosuppression

Progesterone Analogs Megestrol

(Megace®)

400-800mg/day

 

Appetite improvement in 1 week for about 25% of patients

Weight gain: Several weeks if any at all

May help patients with life expectancy >30 days

Small benefit in treating cachexia, mixed results on improving quality of life

Hypertension, edema, CNS effects

Significant risk of increased risk of thromboembolism – DVT/PE for many patients

Serotonin antagonism Mirtazapine

(Remeron®)

7.5-15mg at HS

May stimulate appetite by increasing levels of serotonin

Treating depression may improve appetite

Lack of evidence for cachexia benefit

Dizziness, xerostomia, constipation
Cyproheptadine

(Periactin®)

2-4mg TID

May increase appetite, decrease nausea

Weight gain in first few weeks

Sedation, dizziness

Constipation, urinary retention

 

Synthetic Cannabinoids – THC

 

Dronabinol

(Marinol®)

2.5mg BID, 1 hour before lunch, dinner

Limited evidence in cancer cachexia

Improves food enjoyment

Inferior to megestrol

Tachycardia, hypotension

Psychoactive: dysphoria, hallucinations

Sedation, confusion, perception changes

Assessment and Recommendations

DT’s dose of morphine IR for breakthrough pain is higher than the recommended dose of 10-20 % of the total daily morphine dose. This may be contributing to DT’s complaint of feeling overly sedated when taking morphine. Consider assessing daily morphine use and offering morphine IR at 10-20%.

Patients on chronic opioids may require a more robust regimen for constipation than senna-docusate sodium one tablet daily. Constipation can cause GI upset and decreased appetite. Assess for constipation and consider increasing senna-docusate sodium to twice daily and monitoring bowel movements and signs/symptoms of constipation.

Metformin is known to cause nausea and decreased appetite. The goal of diabetes medications at end of life are to prevent symptomatic hypoglycemia and minimize the risk of hypoglycemia. Tight glucose control provides no benefit at the end of life. Consider deprescribing metformin.

Corticosteroids are most effective for short-term treatment of appetite and are beneficial for feeling of well-being, and for patients with other indications for corticosteroids such as fatigue, dyspnea, cerebral edema, bone pain, and nausea. However, since DT is already taking dexamethasone 8mg twice daily, it is unlikely that increasing the dose or changing to prednisone would provide significant benefit for appetite.

If pharmacotherapy is still desired, options include cyproheptadine 2mg three times daily. However, cyproheptadine has undesirable side effects that may preclude its use (dizziness, sedation, impaired cognition) and is only shown to induce mild appetite stimulation. Megestrol is another option, however, it increases the risk of DVT/PEs, and is most effective long-term (more than 4 weeks) which may preclude its use. Recommended doses start at 400mg daily, often necessitating use of the liquid due to high tablet count. True benefit in patients with a poor prognosis is not understood.

If DT’s prognosis is greater than one month, mirtazapine may be beneficial as it is associated with a greater relief of depressive symptoms within the first month of therapy compared with other antidepressants. Additionally, mirtazapine has an increased likelihood of increasing appetite and weight gain compared with other antidepressants and also treats insomnia.⁵ Other options may also be considered, but do not have as fast an onset for depression (trazodone), require polypharmacy to address all of the patient’s symptoms (sertraline and temazepam), and/or do not have favorable side effect profiles. Consider a trial of mirtazapine 7.5-15mg at bedtime; reassess in 1-2 weeks.

Expert Recommendations

Reduced appetite and weight loss are associated with poor outcomes in the elderly and those with a life-limiting illness. As humans, we want our loved ones to eat, and we want to feed them any way we can. Sometimes, that even means surgically placing a feeding tube to provide nourishment. But goals of care should be thoughtfully revisited. Is the goal to improve nutrition in a body that may no longer be processing nutrients? Is the goal to provide pleasure by feeding the individual his/her favorite foods?

Two expert groups of physicians, The American Geriatric Society (AGS) and the American Academy of Hospice and Palliative Medicine (AAHPM) have each contributed recommendations for other physicians when working with patients and families of aged and or persons at end of life, to a campaign called “Choosing Wisely®,” an initiative of the American Board of Internal Medicine (ABIM) Foundation.

“Don’t recommend percutaneous feeding tubes in patients with advanced dementia; instead, offer oral assisted feeding.”

 The AGS offers one more recommendation on the topic:

“Avoid using prescription appetite stimulants or high-calorie supplements for treatment of anorexia or cachexia in older adults; instead, optimize social supports, discontinue medications that may interfere with eating, provide appealing food and feeding assistance, and clarify patient goals and expectations.”

With these in mind, hospice clinicians should consider permission granted to focus on the comfort of human interaction and connection during assisted feeding instead of meeting nutritional value and goals.

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References

  1. Sousa, Mariana S., et al. “Appetite-related distress is burdensome in the last sixty days of life of people receiving palliative care: A national longitudinal consecutive cohort study.” Journal of Palliative Medicine 25.4 (2022): 636-642. 
  2. Pilgrim, A., et al. “An overview of appetite declines in older people.” Nurs Older People 2025 June; 27(5):29-35 doi:10.7748/nop.27.5.29.e697 
  3. Hospice Foundation of America. A Caregiver’s Guide to the Dying Process. 2022. Washington, DC 
  4. Roeland EJ, Bohlke K, Baracos VE, et al. Management of Cancer Cachexia: ASCO Guideline. J Clin Oncol. 2020;38(21):2438-2453. 
  5. Case report: Mirtazapine Therapy for Dysgeusia in an Elderly Patient: Prim Care Companion J Clin Psychiatry 2006:8(3): 178-180. 
  6. AGS Choosing Wisely Workgroup. “American Geriatrics Society identifies another five things that healthcare providers and patients should question.” Journal of the American Geriatrics Society vol. 62,5 (2014): 950-60. doi:10.1111/jgs.12770 
  7. Fischberg D, Bull J, Casarett D, Hanson LC, Klein SM, Rotella J, Smith T, Storey CP Jr, Teno JM, Widera E; HPM Choosing Wisely Task Force. Five things physicians and patients should question in hospice and palliative medicine. J Pain Symptom Manage. 2013 Mar;45(3):595-605. doi: 10.1016/j.jpainsymman.2012.12.002. Epub 2013 Feb 22. PMID: 23434175.