Can this patient's medications cause altered mental status?

Can These Medications Cause Altered Mental Status?

Yes, multiple medications in this regimen have significant potential to cause altered mental status, particularly pregabalin, fluoxetine, cetirizine, and the combination of centrally-acting agents, which collectively increase the risk of cognitive impairment, delirium, and sedation in this patient. 1

Highest-Risk Medications for Altered Mental Status

Pregabalin (150 mg TID)

• Pregabalin is a centrally-acting gabapentinoid that directly causes sedation, cognitive impairment, and contributes to anticholinergic burden 1
• At 450 mg daily (150 mg TID), this dose significantly increases risk of CNS depression, confusion, and impaired motor coordination 1
• Gabapentinoids are specifically identified as medications with centrally-acting effects that increase fall risk and cognitive impairment in older adults 1
• The combination with other CNS depressants creates additive sedative effects 1

Fluoxetine (20 mg daily)

• Fluoxetine can impair judgment, thinking, and motor skills, with FDA warnings about cognitive and motor performance interference 2
• SSRIs like fluoxetine are associated with hyponatremia, which manifests as altered mental status, confusion, and lethargy 2
• Fluoxetine specifically causes mental status changes including agitation, confusion, and emotional lability, particularly during initiation or dose changes 2
• The drug has a long half-life with active metabolites, meaning effects persist and accumulate over time 2

Cetirizine (5 mg at bedtime)

• Antihistamines like cetirizine have anticholinergic properties that contribute to cognitive impairment and altered mental status 1
• Even "non-sedating" antihistamines can cause CNS effects, particularly when combined with other centrally-acting medications 1
• Anticholinergic burden from multiple medications is associated with decline in cognition, functional status, and increased delirium risk 1

Moderate-Risk Medications

Carvedilol (12.5 mg BID)

• Beta-blockers can cause CNS effects including confusion, depression, and cognitive slowing 1
• Carvedilol crosses the blood-brain barrier and may contribute to lethargy and altered mentation 1

Tamsulosin (0.4 mg daily)

• Alpha-blockers like tamsulosin contribute to orthostatic hypotension, which can manifest as confusion, dizziness, and altered mental status 3
• Orthostatic hypotension is a key contributor to falls and cognitive changes, particularly when combined with other antihypertensives 1

Melatonin (10 mg at bedtime PRN)

• High-dose melatonin (10 mg) can cause excessive sedation, daytime drowsiness, and cognitive impairment 1
• The dose exceeds typical recommendations of 3-5 mg for sleep 1

Cumulative Anticholinergic and Sedative Burden

The combination of multiple medications with anticholinergic and sedative properties creates a "Drug Burden Index" that significantly increases risk of cognitive impairment, delirium, falls, and functional decline 1

Contributing Medications to Total Burden:

• Pregabalin (strong CNS depressant) 1
• Fluoxetine (anticholinergic effects, CNS effects) 2
• Cetirizine (anticholinergic) 1
• Carvedilol (CNS penetration) 1
• Tamsulosin (orthostatic effects) 3
• Melatonin (sedation) 1

This polypharmacy pattern with multiple centrally-acting agents is specifically associated with increased emergency department visits, hospitalizations, confusion, delirium, and falls 1

Medications That Can Cause Delirium in ICU/Hospital Settings

Documented Delirium Risk:

• Benzodiazepines are not on this list, but if they were, they would be highest risk for delirium 1
• Opioids (insulin lispro sliding scale may be used with pain medications elsewhere) are associated with delirium in 64% of confused patients 4
• Gabapentinoids like pregabalin are identified as delirium risk factors 1

Metabolic Medications That Can Indirectly Cause Altered Mental Status

Insulin Lispro (sliding scale)

• Hypoglycemia from insulin causes acute altered mental status, confusion, and loss of consciousness 1, 2
• Fluoxetine can potentiate hypoglycemia, requiring adjustment of insulin dosing 2
• The sliding scale includes instruction to call provider if blood sugar <60 or >400, recognizing AMS risk [@patient medication list@]

Entresto (sacubitril-valsartan 24-26 mg BID)

• Can cause hypotension leading to decreased cerebral perfusion and confusion 1
• Combined with carvedilol and tamsulosin, increases orthostatic hypotension risk 3

Medications With Lower Direct CNS Risk

Minimal Direct AMS Risk:

• Allopurinol [@patient medication list@]
• Aspirin 81 mg [@patient medication list@]
• Atorvastatin 1
• Apixaban [@patient medication list@]
• Ferrous sulfate [@patient medication list@]
• Omeprazole [@patient medication list@]
• Potassium chloride [@patient medication list@]
• Acetaminophen 1
• Docusate/Miralax [@patient medication list@]
• Multivitamin [@patient medication list@]

Critical Clinical Pitfalls

Polypharmacy-Related Delirium:

Patients taking 5 or more medications (this patient takes 15+ regular medications) have significantly increased risk of adverse drug events, cognitive impairment, functional decline, and death 1

Prescribing Cascade Recognition:

• If this patient develops confusion, do not add an antipsychotic without first considering medication-induced delirium 1
• Altered mental status in a patient on multiple CNS-active drugs should prompt medication review and deprescribing before adding new agents 1

Drug-Drug Interactions:

• Fluoxetine inhibits CYP2D6, potentially increasing levels of carvedilol and other medications, amplifying CNS effects 2
• Multiple medications affecting blood pressure (carvedilol, Entresto, tamsulosin) increase orthostatic hypotension risk 1, 3

Monitoring Recommendations

Immediate Assessment if AMS Develops:

• Check blood glucose immediately (hypoglycemia from insulin + fluoxetine interaction) 2
• Assess orthostatic vital signs (multiple antihypertensives) 1, 3
• Review medication administration timing and recent additions/changes 1
• Check sodium level (fluoxetine-induced hyponatremia) 2
• Evaluate for infection, as this patient has multiple risk factors for delirium 1, 4

Deprescribing Considerations:

In older adults with polypharmacy, strongly anticholinergic medications and sedating drugs should be prioritized for discontinuation or dose reduction 1

• Consider reducing pregabalin dose or frequency 1
• Evaluate necessity of cetirizine (anticholinergic burden) 1
• Consider melatonin dose reduction to 3-5 mg 1
• Review need for tamsulosin given orthostatic risk 3