What safe medications can be used to treat insomnia and loss of appetite in an older adult with Alzheimer disease who is already receiving a cholinesterase inhibitor (e.g., donepezil) or memantine?

Safe Medications for Sleep and Appetite in Alzheimer's Disease

Critical First Step: Address Reversible Medical Causes Before Adding Medications

Before prescribing any medication for insomnia or appetite loss, you must systematically investigate and treat underlying medical contributors that commonly drive these symptoms in Alzheimer's patients who cannot verbally communicate discomfort. 1

Medical Workup Required:

• Pain assessment and management – untreated pain is a major driver of sleep disturbance and appetite loss in dementia patients 2
• Screen for infections – urinary tract infections and pneumonia frequently cause behavioral changes and appetite loss 2
• Check for constipation and urinary retention – both significantly contribute to restlessness and poor appetite 1, 2
• Evaluate metabolic disturbances – dehydration, electrolyte abnormalities, and hypoxia worsen confusion and appetite 2
• Medication review – identify and discontinue anticholinergic agents (diphenhydramine, oxybutynin, cyclobenzaprine) that worsen confusion, appetite, and sleep 1

Cholinesterase Inhibitor Consideration:

Review whether the current cholinesterase inhibitor (donepezil) is contributing to appetite loss. Patients on cholinesterase inhibitors experience a slightly increased risk of weight loss, and individual vulnerable patients may experience severe weight loss. 1 However, this does not appear relevant for the majority of patients. 1

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Non-Pharmacological Interventions: First-Line Treatment

Non-pharmacological interventions must be attempted and documented as failed before considering medications for sleep or appetite problems. 2

For Sleep Disturbances:

• Increase daytime bright light exposure – 2 hours of morning bright light at 3,000-5,000 lux decreases daytime napping, increases nighttime sleep, and reduces agitated behavior 2
• Avoid bright light in the evening to consolidate the sleep-wake cycle 2
• Ensure adequate lighting during late afternoon to reduce nighttime awakenings 2
• Increase daytime physical and social activities – at least 30 minutes of sunlight exposure daily provides temporal cues 2
• Reduce time in bed during the day to consolidate nighttime sleep 2
• Establish predictable daily routines including a structured bedtime routine 2

For Appetite Loss:

• Encourage shared meals – eating in company stimulates dietary intake and improves quality of life 1
• Provide verbal prompting to remember to eat and drink 1
• Support with shopping and meal preparation – consider meals on wheels or shared meals 1
• Ensure adequate pain management before mealtimes 1
• Avoid dietary restrictions that may limit food or fluid intake, as these are potentially harmful 1

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Pharmacological Options: When Non-Pharmacological Approaches Fail

For Insomnia in Alzheimer's Disease:

Avoid benzodiazepines (including alprazolam, lorazepam) for routine sleep management in Alzheimer's patients. They increase delirium incidence and duration, cause paradoxical agitation in approximately 10% of elderly patients, worsen cognitive function, and increase fall risk. 2

Avoid trazodone despite its widespread off-label use. Trazodone has no systematic evidence for effectiveness in insomnia, and risks outweigh benefits in elderly patients, including orthostatic hypotension, cardiac arrhythmias, falls, and extrapyramidal symptoms even at low doses. 3

Safer Alternatives for Insomnia:

• Melatonin receptor agonists are preferred over sedating medications 3
• Mirtazapine 7.5-15 mg at bedtime may be considered if a sedating antidepressant is needed, though evidence specifically for insomnia is relatively weak 3
• Behavioral therapy for insomnia should be first-line 3

Common Pitfall: Do not use PRN dosing of sedating medications without clear parameters, as this increases confusion and fall risk. 3

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For Appetite Loss in Alzheimer's Disease:

There are no FDA-approved medications specifically to stimulate appetite in Alzheimer's disease. The focus should remain on:

1. Treating reversible medical causes (pain, infections, constipation, dehydration) 1
2. Reviewing medications that may suppress appetite – opioids, sedatives, digoxin, metformin, antibiotics, NSAIDs, and cholinesterase inhibitors can all affect appetite 1
3. Reducing or replacing medications with adverse effects on appetite 1
4. Dietary counseling to support a generally healthy diet 1

If the patient is on a cholinesterase inhibitor and experiencing severe weight loss, consider whether the individual patient has increased vulnerability to this side effect. 1 However, do not discontinue cholinesterase inhibitors without careful consideration, as they provide cognitive benefits. 4, 5

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Monitoring Fluid Intake

Older persons with dementia experience less thirst and marked vulnerability for dehydration, which can be worsened by sedatives. 1

• Provide verbal prompting to remember to drink 1
• Monitor for excessive fluid losses due to diuretics 1
• Ensure adequate hydration before considering any medication changes 2

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What NOT to Do

• Do not add sedatives (benzodiazepines, trazodone) without first addressing reversible medical causes and attempting non-pharmacological interventions 2, 3
• Do not assume medications are safe simply because they are commonly prescribed (e.g., trazodone) 3
• Do not continue medications indefinitely – review need at every visit 2
• Do not overlook polypharmacy as a contributor to malnutrition and sleep disturbance 1

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Bottom Line

For an Alzheimer's patient with insomnia and appetite loss already on donepezil or memantine, the safest approach is to systematically investigate and treat reversible medical causes (pain, infection, constipation, dehydration, medication side effects) and implement intensive non-pharmacological interventions before considering any additional medications. 1, 2 If pharmacotherapy becomes necessary for insomnia after behavioral approaches fail, melatonin receptor agonists are preferred over benzodiazepines or trazodone. 3 For appetite loss, focus on treating underlying causes, medication review, and dietary counseling rather than adding appetite stimulants. 1