What medications can affect cognitive or physical ability and what are their potential side effects?

Medications That Impair Cognitive and Physical Ability

Benzodiazepines, anticholinergic medications, and opioids are the most problematic drug classes affecting cognitive and physical ability in older adults, causing sedation, cognitive impairment, falls, and motor skill deficits that significantly increase morbidity and mortality risk. 1

High-Risk Medication Classes

Benzodiazepines and Related Agents

• Cause sedation, cognitive impairment, unsafe mobility with injurious falls, and motor skill impairment 1
• Lead to dependence, withdrawal syndromes including sleep disruption, and increased risk of vehicle crashes 1
• Lorazepam causes paradoxical agitation in approximately 10% of elderly patients 2
• Long-acting agents like diazepam should be avoided entirely; moderate-acting agents (lorazepam, clonazepam) also carry substantial risk 1
• Benzodiazepine-like GABA receptor hypnotics (zolpidem, zaleplon) share similar adverse effects 1

Anticholinergic Medications

• Cause broad muscarinic receptor blockade resulting in CNS impairment, delirium, slowed comprehension, impaired vision, urinary retention, constipation, sedation, and falls 1
• First-generation antihistamines (diphenhydramine, hydroxyzine) are particularly problematic, impairing driving ability and leading to cognitive decline, especially in elderly patients 1
• Muscle relaxants (cyclobenzaprine, metaxalone) share these anticholinergic properties 1
• Overactive bladder medications like oxybutynin carry significant anticholinergic burden 1
• H1R and H2R blocking agents with anticholinergic effects are associated with cognitive decline that worsens in elderly populations 1

Opioids

• Cause sedation, anticholinergic properties, cognitive impairment, and falls 1
• Lead to addiction, withdrawal syndrome, and increased risk of opioid-use disorder, overdose, myocardial infarction, and motor vehicle injury 1
• Both short-acting and slow-release formulations (morphine, oxycodone, codeine) carry these risks 1

Antipsychotics

• Worsen cognitive function in dementia and should be avoided as first-line agents for cognitive behavioral problems 1
• Typical agents (chlorpromazine, haloperidol) and atypical agents (quetiapine, risperidone, olanzapine) all carry FDA box warnings for risk of death when used for dementing disorders 1
• Most sedating agents should be avoided entirely 1

Moderate-Risk Medications

NSAIDs

• Indomethacin is the most problematic NSAID, causing neurotoxicity and CNS effects 1
• All NSAIDs (naproxen, ibuprofen) worsen kidney clearance, hypertension, heart failure, and cause GI ulceration/bleeding 1
• Poorly tolerated in older adults with higher risk of adverse effects 1

Antihypertensive Agents

• Any class can cause blood pressure drops leading to falls, injury, and orthostasis 1
• Older agents (reserpine, clonidine) have negative effects on cognition 3
• Commonly used agents (thiazides, calcium antagonists, ACE inhibitors, beta-blockers) have minimal cognitive effects but still carry fall risk 3

Antidiabetic Medications

• Sulfonylureas (glyburide, glipizide) accumulate in chronic kidney disease with higher risk of hypoglycemia 1
• Short-acting and peak insulins accumulate in acute and chronic kidney injury, causing hypoglycemic risk 1
• Severe hypoglycemia is associated with reduced cognitive function and stepwise increase in dementia risk 1

Cholinesterase Inhibitors

• Donepezil causes nausea, vomiting, diarrhea, nightmares, and bradyarrhythmia 1, 4
• Common adverse reactions include insomnia, dizziness, confusion, somnolence, and urinary incontinence 4
• Lack long-term benefit, particularly in advanced dementia 1
• Safe to taper to off when there is perceived lack of benefit 1

Antiepileptic Drugs

• Topiramate has clear evidence of affecting cognitive function with specific effects on attention and verbal function 5
• All commonly used AEDs have some effect on cognitive function, which may be substantial when crucial functions are involved 5
• Effects are particularly problematic for learning in children, driving ability in adults, and memory in elderly patients 5

Clinical Management Algorithm

Step 1: Medication Review

• Maintain an updated medication list including nonprescription drugs for regular review 1
• Review medication lists regularly in patients with cognitive impairment, as medications can affect cognitive function 1
• One RCT found medication list review significantly decreases inappropriate prescribing (P < 0.001 at 12 months) 1

Step 2: Identify Reversible Causes

• Screen for depression, vitamin B deficiency, and hypothyroidism in patients with cognitive impairment 1
• Consider structural neuroimaging to identify lesions in recently diagnosed patients 1
• Evaluate for delirium before attributing cognitive changes to dementia 1

Step 3: Assess Fall Risk

• Ask all older adults about falls and document basic falls evaluation including medication review 1
• Psychotropic medication withdrawal can lead to significant reduction in fall risk 1
• Examine potentially reversible causes including medications and environmental factors 1

Step 4: Deprescribing Strategy

• Taper benzodiazepines using EMPOWER technique; consider cognitive behavioral therapy for anxiety and sleep 1
• Taper antipsychotics when possible, especially for pharmacological behavioral control in cognitive disease; use redirection and other non-pharmacological agents 1
• Consider safer alternatives: newer antidepressants (SSRIs) have not shown negative effects on cognition 3
• For pain management, scheduled acetaminophen may ameliorate moderate musculoskeletal pain in elderly patients 1

Critical Pitfalls to Avoid

• Do not prescribe cholinesterase inhibitors concurrently with anticholinergic medications - 14% of patients on cholinesterase inhibitors were also taking medications with anticholinergic properties, directly counteracting therapeutic intent 6
• Avoid first-generation antihistamines entirely in older adults - despite evidence and recommendations, they continue to be prescribed in elderly patients with cognitive impairments 1, 6
• Do not use benzodiazepines for breakthrough agitation in dementia - paradoxical agitation occurs in 10% of elderly patients, and risks outweigh benefits 2
• Monitor for cognitive decline as indicator of medication toxicity - difficulties with diabetes self-care or MMSE scores below 24 points indicate need for immediate medication review 1