Why is a medication review indicated in an older patient with altered mental status and polypharmacy?

Medication Review in Altered Older Patients with Polypharmacy

Medications are a leading reversible cause of altered mental status in older adults, and comprehensive medication review should be performed immediately in any older patient presenting with cognitive impairment, delirium, falls, depression, or urinary incontinence, as drugs may directly cause or significantly exacerbate these geriatric syndromes through anticholinergic effects, sedation, drug-drug interactions, and drug-disease interactions. 1

Primary Rationale: Medications as Direct Causative Agents

High-Yield Reversible Causes

• Benzodiazepines cause sedation, cognitive impairment, unsafe mobility with injurious falls, and motor skill impairment, with long-acting agents like diazepam requiring complete avoidance and moderate-acting agents like lorazepam and clonazepam carrying substantial risk. 2
• Anticholinergic medications cause broad muscarinic receptor blockade resulting in CNS impairment, delirium, slowed comprehension, impaired vision, urinary retention, constipation, sedation, and falls, with first-generation antihistamines like diphenhydramine and hydroxyzine being particularly problematic. 2
• Opioids cause sedation, anticholinergic properties, cognitive impairment, and falls, representing a major cause of delirium in postoperative patients. 2, 3
• Drug-induced delirium occurs in 11-30% of elderly hospital patients, and medication toxicity accounts for 2-12% of patients presenting with suspected dementia. 3

Epidemiological Evidence for Medication-Induced Geriatric Syndromes

• Epidemiological evidence shows that medications may contribute to or exacerbate geriatric syndromes alone or through drug-drug or drug-disease interactions, with medication use (particularly those with sedating effects) often cited as a risk factor for falls. 1
• The total burden of anticholinergic drugs may determine development of delirium rather than any single agent, and anticholinergic effects have been identified in many drugs not classically thought to have major anticholinergic properties. 3
• Polypharmacy is associated with drug-to-drug interactions, drug-to-disease interactions, medication nonadherence, increased healthcare utilization, cognitive impairment, functional decline, and death. 1

Guideline-Mandated Indications for Medication Review

Specific Clinical Triggers

• The American Geriatrics Society explicitly recommends that the medication list of an older adult with diabetes who presents with depression, falls, cognitive impairment, or urinary incontinence should be reviewed. 1
• Clinicians should assess older adults with diabetes for cognitive impairment using a standardized screening instrument during the initial evaluation period and with any significant decline in clinical status, with increased difficulty with self-care considered a change in clinical status. 1
• The medication list of an older adult with diabetes who has cognitive impairment should be reviewed regularly, as medications can affect cognitive function. 1

Systematic Review Requirements

• Regular monitoring of drug efficacy and safety is critical to prevent adverse drug reactions and improve quality of life and clinical outcomes, with structured periodic reviews of all medications matching each medication to the patient's comorbidities and goals of care. 1
• In the outpatient setting, a comprehensive medication review should be performed annually, with the availability of an updated medication list including over-the-counter drugs, vitamins, and herbal supplements allowing healthcare providers to evaluate the need for current medications, potential for drug-drug and drug-disease interactions, and ways to enhance medication adherence. 1

Polypharmacy as a Risk Multiplier

Drug-Drug and Drug-Disease Interactions

• The incidence of drug-drug interactions increases with the number of medications (10.9% when 2-4 drugs are used and 80.8% if ≥10 drugs are used), with median drug-drug interaction prevalence rates for hospital admissions and hospital visits of 22.2% and 8.9%, respectively. 1
• Before prescribing a new drug in older people, it is necessary to review the medications already prescribed and consider the possible interactions that the new drug might produce, as any new symptom in older people should be considered a possible adverse drug reaction until proven otherwise. 1
• Factors such as advanced age, female sex, multiple chronic medical conditions, cognitive impairment, low body weight, creatinine clearance less than 50 mL/min, frailty, lack of medical knowledge, multiple prescribers and pharmacies, and concurrent use of 9 or more medications can increase the risk of an adverse drug event due to polypharmacy. 1

The Prescribing Cascade

• The prescribing cascade occurs when an adverse drug reaction is erroneously perceived as a new medical condition, leading to prescription of an additional medication or unnecessary diagnostic test that may lead to inappropriate intervention, adding pill burden, increasing healthcare utilization, and causing preventable adverse drug events. 1
• Before adding a new drug, prescribers should keep in mind that any new symptom in older people should be considered a possible adverse drug reaction until proven otherwise. 1

Specific High-Risk Medications Requiring Immediate Review

CNS-Active Medications

• There is a high rate of use of CNS-active drugs in patients with cognitive impairment, despite the fact that these medications may worsen cognition and be a possible "reversible" cause of memory loss. 4
• 22% of patients in memory disorders clinics are taking ≥1 contraindicated medication that could potentially affect their cognition, with the most frequently prescribed being benzodiazepines, oxybutynin, amitriptyline, fluoxetine, and diphenhydramine. 4
• 14% of patients being treated with a cholinesterase inhibitor are also taking ≥1 medication with anticholinergic properties, directly counteracting the intended therapeutic effect. 4

Cardiovascular and Metabolic Medications

• Medications with sedating effects are often cited as risk factors for falls, and psychotropic medication withdrawal can lead to significant reduction in fall risk. 1
• Sulfonylureas like glyburide and glipizide accumulate in chronic kidney disease with higher risk of hypoglycemia, and severe hypoglycemia is associated with reduced cognitive function and stepwise increase in dementia risk. 2
• Indomethacin is the most problematic NSAID, causing neurotoxicity and CNS effects, with all NSAIDs worsening kidney clearance, hypertension, heart failure, and causing GI ulceration/bleeding. 2

Practical Implementation Algorithm

Immediate Actions

1. Obtain a complete medication list including over-the-counter drugs, vitamins, herbal supplements, and complementary/alternative medicines to evaluate the need for current medications, potential for drug-drug and drug-disease interactions. 1
2. Identify and immediately discontinue or taper all medications that impair cognition, as this is often the most reversible cause of memory deficits in adults, including benzodiazepines (relative risk 1.5), sedative-hypnotics (hazard ratio 2.1), and anticholinergic medications. 5
3. Review for potentially inappropriate medications using the American Geriatrics Society Beers Criteria, which provide clinicians with information on potentially inappropriate medications in older adults. 1

Systematic Evaluation

• Match each medication to the patient's comorbidities and goals of care, evaluating whether there is evidence-based indication, whether the indication has expired, whether the medication achieves therapeutic goals, and whether it causes unacceptable adverse drug reactions. 1
• Assess for medications that can treat several conditions simultaneously (e.g., beta-blockers in patients with hypertension, angina, heart failure, and atrial fibrillation) to simplify complex treatments. 1
• Consider deprescribing when the existing or potential harm of a medication outweighs the benefit, with systematic deprescribing efforts benefiting nursing home residents. 1

Critical Pitfalls to Avoid

• Do not attribute altered mental status to "dementia progression" without first conducting a thorough medication review, as 2-12% of patients presenting with suspected dementia have medication toxicity as the cause. 3
• Do not overlook over-the-counter medications, vitamins, and herbal supplements, as these contribute significantly to polypharmacy and drug-drug interactions. 1
• Do not delay medication review while pursuing other diagnostic workup, as medication-induced cognitive impairment can be immediately reversible upon discontinuation of the offending agent. 3
• Do not assume that medications prescribed by specialists or continued from hospital discharge are appropriate, as 44% of patients receive at least 1 potentially inappropriate medication at hospital discharge (mainly due to lack of indication). 1
• Do not ignore the cumulative anticholinergic burden, as the total burden of anticholinergic drugs may determine development of delirium rather than any single agent. 3