Despite years of guidelines cautioning against their use, potentially inappropriate central nervous system (CNS)-active medications are commonly prescribed to older adults —particularly those with cognitive impairment — highlighting persistent gaps in medication safety and substantial opportunities for deprescribing in routine clinical practice.

Investigators found that 1 in 4 Medicare recipients with dementia are prescribed these high-risk medications, and over two thirds of these prescriptions lacked a documented clinical indication.

The findings indicate “high levels of potentially inappropriate and harmful prescribing,” senior study investigator John N. Mafi, MD, Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, UCLA, said in a press release.

However, the overall number of seniors receiving these prescriptions has fallen over time, a trend Mafi said was encouraging.

The findings were published online on January 12 in JAMA.

An Opportunity to Improve Safety

For decades, clinical guidelines have warned against high-risk CNS-active medications due to their association with delirium, falls, and hospitalization — risks that are especially pronounced in older adults with cognitive impairment.

To assess whether long-standing guideline warnings have translated into meaningful changes in real-world prescribing and to identify opportunities to reduce medication-related harm, the researchers used Medicare fee-for-service claims from 2013 to 2021 in 4842 adults aged 65 years or older with normal cognition, cognitive impairment with no dementia (CIND), or dementia.

The researchers assessed the proportion of beneficiaries receiving one or more potentially inappropriate CNS-active prescriptions with a supply of at least 28 days, categorized into five drug classes: antidepressants with strong anticholinergic properties, antipsychotics, barbiturates, benzodiazepines, and nonbenzodiazepine hypnotics.

After adjusting for age, sex, race and ethnicity, cognition, comorbidities, and socioeconomic status, the results showed 19.9% (95% CI,18.1%-21.6%) of beneficiaries received one or more potentially inappropriate CNS-active prescriptions in 2013, which decreased to 16.2% (95% CI, 14.3%-18.1%) in 2021 — a decline of 3.7 percentage points (P = .003).

When prescribing trends were examined by drug class from 2013 to 2021, benzodiazepine use declined from 11.4% (95% CI, 10.0%-12.8%) to 9.1% (95% CI, 7.6%-10.5%; P = .02), while nonbenzodiazepine hypnotic use fell more sharply from 7.4% (95% CI, 6.2%-8.6%) to 2.9% (95% CI, 2.1%-3.8%; P < .001). 

In contrast, there were no significant changes in prescribing rates for antipsychotics (2.6% [95% CI, 1.9%-3.3%] to 3.6% [95% CI, 2.7%-4.6%]; P = .07) or barbiturates (0.4% [95% CI, 0.06%-0.6%] to 0.3% [95% CI, 0.03%-0.5%]; P = .40).

Rates remained particularly concerning among patients with cognitive impairment. Compared with beneficiaries with normal cognition (17.0%; 95% CI, 15.6%-18.3%), those with CIND were significantly more likely to receive potentially inappropriate CNS-active prescriptions (21.7%; 95% CI, 19.3%-24.2%; P < .001), as were beneficiaries with dementia (25.1%; 95% CI, 21.4%-28.9%; P < .001).

Patients with cognitive impairment face a higher risk of having adverse effects from these drugs. “These results underscore substantial opportunities to improve the quality and safety of care for millions of older Americans,” said Mafi.

The proportion of prescriptions with a documented clinical indication did not differ significantly between 2013 (6.0%) and 2021 (5.5%).

However, among the 16.2% of beneficiaries receiving potentially inappropriate CNS-active prescriptions in 2021, 11.4% (70.4%) lacked clinical indications.

The authors noted several limitations. Medicare Advantage data were unavailable, clinical information may have been incomplete, and the analysis focused on prescribing prevalence rather than cumulative medication exposure.

The study was funded by the National Institutes of Health/National Institute on Aging. The investigators reported no relevant financial disclosures.