In a 70‑80‑year‑old female with Parkinson disease, type 2 diabetes, atrial fibrillation on apixaban, COPD, pulmonary embolism, neuropathy, osteoporosis, and chronic pain, currently taking duloxetine 60 mg AM + 30 mg HS, hydroxyzine pamoate 25 mg three times daily, clonazepam 0.5 mg nightly, melatonin 10 mg nightly, donepezil 5 mg daily, carbidopa/levodopa 25/100 mg twice daily, extended‑release carbidopa/levodopa (Rytary) regimen, mirabegron (Myrbetriq) 25 mg daily, simvastatin 40 mg nightly, omeprazole 40 mg daily, apixaban 2.5 mg twice daily, dulaglutide (Trulicity) 0.75 mg weekly, and PRN (as needed) tramadol and oxycodone, what is your assessment of the appropriateness of this medication list and what recommendations would you make to reduce sedation, anticholinergic load, fall risk, and bleeding risk?

Critical Medication Safety Concerns in This Elderly Parkinson's Patient

This medication regimen poses substantial risks for falls, sedation, cognitive decline, and bleeding complications that require immediate systematic review and deprescribing. The combination of multiple anticholinergic agents, benzodiazepines, opioids, and sedating medications creates a dangerous polypharmacy burden in a frail elderly patient with Parkinson's disease.

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Highest Priority Safety Issues

1. Excessive Anticholinergic Burden – IMMEDIATE CONCERN

Hydroxyzine 25 mg TID (scheduled) is highly inappropriate and must be discontinued. 1

• Hydroxyzine is a strongly anticholinergic antihistamine that causes CNS impairment, delirium, slowed comprehension, vision impairment, urinary retention, constipation, sedation, and falls in elderly patients 1
• The Drug Burden Index demonstrates that anticholinergic medications are associated with decline in cognition, functional status, and ADL scores 1
• Scheduled TID dosing (75 mg total daily) is particularly dangerous – this creates continuous anticholinergic exposure rather than PRN use 1
• Hydroxyzine worsens confusion and agitation in dementia patients and should be minimized or discontinued 2

Mirabegron (Myrbetriq) 25 mg daily for overactive bladder is acceptable – unlike oxybutynin, mirabegron is a beta-3 agonist without anticholinergic properties, making it the preferred agent for this indication in elderly patients 1

2. Benzodiazepine Use – HIGH RISK

Clonazepam 0.5 mg nightly requires careful reassessment despite its indication for REM sleep behavior disorder. 1

• Clonazepam is listed on the American Geriatrics Society Beers Criteria as potentially inappropriate in older adults 1
• Concerning side effects include morning sedation, gait imbalance/falls, depression, cognitive disturbances (delirium, amnesia), and exacerbation of sleep-disordered breathing 1
• Progressive cognitive decline combined with age-related impairment in drug metabolism often leads to gradual intolerance 1
• However, clonazepam has conditional recommendation for secondary RBD in Parkinson's disease 1

Alternative approach: Consider switching to immediate-release melatonin 3-15 mg, which is only mildly sedating with fewer side effects (vivid dreams, sleep fragmentation) and may be more appropriate for older patients with neurodegenerative disease 1

• The patient is already taking melatonin 10 mg nightly, which could potentially be optimized instead of continuing clonazepam 1

3. Opioid Burden – FALL AND SEDATION RISK

PRN tramadol and oxycodone create additive sedation, anticholinergic properties, cognitive impairment, and fall risk. 1

• Both opioids share sedation and anticholinergic properties 1
• Opioids cause cognitive impairment and falls in elderly patients 1
• Scheduled acetaminophen 650-1000 mg TID should be the foundation of chronic pain management before escalating to opioids 1
• Moderate musculoskeletal pain in elderly patients may be ameliorated by scheduled acetaminophen 1

4. Donepezil in Advanced Parkinson's Disease – QUESTIONABLE BENEFIT

Donepezil 5 mg daily requires reassessment of ongoing benefit versus adverse effects. 1

• Cholinesterase inhibitors are indicated for mild to moderate dementia but lack long-term benefit, particularly in advanced dementia 1
• Adverse effects include nausea, vomiting, diarrhea, nightmares, and bradyarrhythmia 1
• If there is perceived lack of benefit, it is safe to taper to off 1
• However, rivastigmine (another cholinesterase inhibitor) has conditional recommendation for secondary RBD in Parkinson's disease with dementia 1

5. Bleeding Risk with Anticoagulation

Apixaban 2.5 mg BID on top of multiple fall-risk medications creates substantial bleeding risk. 1

• The combination of anticoagulation with medications that increase fall risk (hydroxyzine, clonazepam, opioids, duloxetine) substantially elevates intracranial hemorrhage risk 1
• Fall risk assessment must be performed at every visit when patients are on anticoagulation 1
• NSAIDs should be strictly avoided due to GI ulceration/bleeding risk and worsening of kidney disease, hypertension, and heart failure 1

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Specific Deprescribing Recommendations

DISCONTINUE IMMEDIATELY:

1. Hydroxyzine 25 mg TID – Replace with non-pharmacologic anxiety management or consider low-dose SSRI if chronic anxiety requires treatment 1, 2

TAPER AND REASSESS:

1. Clonazepam 0.5 mg nightly – Consider gradual taper using EMPOWER technique while optimizing melatonin dosing (already at 10 mg) 1

   • If REM sleep behavior disorder symptoms worsen, consider rivastigmine as alternative (addresses both cognition and RBD) 1

2. Donepezil 5 mg daily – Taper to off if no perceived cognitive benefit, especially if patient has advanced dementia 1

3. PRN opioids (tramadol, oxycodone) – Implement scheduled acetaminophen 650-1000 mg TID as foundation, reserve opioids for breakthrough severe pain only 1

OPTIMIZE:

1. Duloxetine 60 mg AM + 30 mg HS (total 90 mg daily) – This is appropriate for diabetic neuropathy and depression/anxiety 1

   • Duloxetine 60-120 mg/day has confirmed efficacy in painful diabetic peripheral neuropathy 1
   • Continue current regimen but monitor for sedation and fall risk 1

2. Melatonin 10 mg nightly – Already at appropriate dose for RBD (3-15 mg range) 1

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Parkinson's Disease Medication Assessment

APPROPRIATE:

• Carbidopa/Levodopa 25/100 mg BID plus Rytary (extended-release) regimen – This is the mainstay of Parkinson's treatment 3, 4, 5, 6
• Levodopa is the most effective medication for motor symptoms of Parkinson's disease 3, 5, 6
• Combination of standard-release during day and extended-release at night is appropriate for older patients 4

CAUTION:

• Monitor for levodopa-related motor complications (dyskinesias, motor fluctuations, "off periods") 3, 7, 6
• Assess for hallucinations/psychosis – if present, quetiapine (off-label) or clozapine (evidence-based) are the only appropriate antipsychotics 4, 6
• Never use typical antipsychotics or most atypical antipsychotics in Parkinson's disease patients 4

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Monitoring and Safety Algorithm

DAILY/WEEKLY MONITORING:

1. Falls risk assessment – Document any falls, near-falls, orthostatic symptoms 1
2. Cognitive function – Monitor for delirium, confusion, memory worsening 1
3. Sedation level – Assess daytime alertness, functional independence 1
4. Pain control – Ensure adequate analgesia with scheduled acetaminophen before PRN opioids 1

MONTHLY MONITORING:

1. Anticholinergic burden score – Recalculate after medication changes 1
2. Medication necessity – Review each medication for ongoing indication 1
3. Parkinson's motor symptoms – Assess tremor, rigidity, bradykinesia control 3, 6
4. Nonmotor symptoms – Screen for depression, anxiety, sleep disturbances, constipation 3, 6

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Common Pitfalls to Avoid

• Do not add medications without first deprescribing inappropriate agents 1, 2
• Do not use anticholinergic medications for anxiety in elderly patients – they worsen cognition and increase fall risk 1
• Do not use benzodiazepines for routine anxiety management except for alcohol/benzodiazepine withdrawal 1, 2
• Do not prescribe typical antipsychotics or most atypical antipsychotics in Parkinson's disease (only quetiapine or clozapine if psychosis develops) 4, 6
• Do not continue medications indefinitely – attempt taper within 3-6 months to reassess necessity 1, 2