Drug-related cognitive impairment is common in routine practice and should be considered in any individual receiving drug therapy who presents with cognitive symptoms. These effects can occur at any age and are associated with a wide range of medications. The long-term use of benzodiazepines, antidepressants with anticholinergic properties, and antipsychotics has been associated with cognitive decline, particularly in older adults. Although these impairments may be preventable through baseline cognitive assessment and regular monitoring, they are often mistaken for age-related or neurodegenerative conditions and therefore remain underrecognized.

A literature review examined the clinical features and drug classes involved, highlighting the potential long-term consequences when these effects are not identified and managed.

High Burden

Medication-related cognitive impairment is more prevalent than often assumed. Drugs are the leading cause of delirium and may account for up to 30% of cases in hospitalized older adults. Thus, polypharmacy doubles the risk.

Medication-related dementia accounts for an estimated 2.7%-10% of dementia cases. Earlier studies have suggested that medications may represent the most common cause of reversible dementia, contributing to 28.2% of the cases. With increasing prescriptions and a higher number of medications per person, the burden is likely to be greater.

The risk increases sharply with the number of medications prescribed, increasing ninefold in individuals receiving four or more drugs. Polypharmacy affects approximately 29% of individuals aged 65 years or older and nearly 42% of those aged 85 years or older.

Clinical Features

Drug-induced cognitive impairment can affect multiple domains including memory, attention deficits, disorientation in time or space, and episodes of confusion. Individuals who may present with confusion, language difficulties, slowed thinking, reduced processing speed, and motor slowing are also among the cognitive impairments associated with medication.

The severity ranges from mild cognitive impairment to dementia. In some cases, symptoms present acutely as delirium with hallucinations, illusions, or altered perception.

These impairments can appear shortly after drug initiation or may develop gradually. Severity often correlates with plasma drug concentration. Symptoms typically improve after dose reduction or discontinuation, although persistence for months or longer has been reported.

High-Risk Drugs

Multiple drug classes have been associated with an increased risk for cognitive impairment, including antiepileptics, antidepressants, antiparkinsonian agents, antipsychotics, lithium, benzodiazepines, opioids, first-generation antihistamines, anticholinergics used for urinary incontinence, proton pump inhibitors, glucocorticoids, nonsteroidal anti-inflammatory drugs, statins, antihypertensives, and anticancer therapies.

A 2023 literature review assessed the cognitive safety of psychotropic medications in older adults and found that individuals with depression who had no baseline cognitive impairment were at greater risk for cognitive decline when treated with tricyclic antidepressants or selective serotonin reuptake inhibitors, particularly paroxetine, for at least 6 months compared with those not receiving these medications. These findings suggest that medications, rather than depression itself, may contribute to the decline, potentially through their anticholinergic effects.

Benzodiazepines, especially those with a long half-life of at least 20 hours, have also been associated with cognitive decline. Although the effect size appears modest, patients should be informed of the potential long-term effects of these treatments.

Most studies have reported significant cognitive decline in older adults treated with antipsychotics, with a risk approximately double that of healthy individuals or equivalent to 1 year of neurodegenerative disease progression. This association has been observed for both conventional and atypical antipsychotics. The combination of antipsychotics with other psychotropic medications has also been linked to cognitive decline in older adults.

Clinical Implications

Only 6.5% of clinical trials evaluating medications assess cognitive safety, and most of the available data are from studies of benzodiazepines and antidepressants.

Experts recommend systematic cognitive assessment before prescribing these medications and then regularly throughout treatment. Comprehensive evaluation across multiple domains, ideally conducted by a neuropsychologist, is preferable, such as the Mini-Mental State Examination or the Montreal Cognitive Assessment.

This story was translated from Univadis France, part of the Medscape Professional Network.