Risky CNS-Active Drugs Still in the Mix for Dementia Patients

 

• One in four dementia patients received a potentially inappropriate central nervous system-active drug prescription, Medicare data suggested.
• However, prescribing rates, notably for benzodiazepines and nonbenzodiazepine hypnotic drugs, fell over 9 years.
• Despite this encouraging decline, over two-thirds of patients receiving these prescriptions lacked a documented clinical indication in 2021.

One in four dementia patients received a potentially inappropriate drug prescription, an analysis of Medicare claims data suggested.

Overall, 25.1% of people with dementia and 21.7% of those with other forms of cognitive impairment were prescribed at least one central nervous system (CNS)-active drug from 2013 to 2021, reported John Mafi, MD, MPH, of the David Geffen School of Medicine at the University of California Los Angeles, and colleagues.

Significantly fewer older adults who were cognitively normal (17%) received a prescription for a CNS-active drug, they wrote in a JAMA research letter.

Across all Medicare beneficiaries, prescriptions for CNS-active drugs fell from 19.9% to 16.2% over the 9-year study period (P=0.003).

"While this decline was encouraging, over two-thirds of patients receiving these prescriptions lacked a documented clinical indication in 2021, the end of the study period, suggesting high levels of potentially inappropriate and harmful prescribing," Mafi said in a statement.

"Compared with patients with normal cognition, we also found higher levels of prescribing among older adults with cognitive impairment, who face a higher risk of adverse effects from these drugs," he added.

CNS-active drugs are associated with an increased risk of falls, delirium, and hospitalization. They are often prescribed for dementia patients, despite warnings reported in the American Geriatrics Society (AGS) Beers Criteria.

"Guidelines emphasize non-pharmacologic strategies as first-line management of dementia-related agitation," Mafi noted. "On the health system side, clinical decision support tools in electronic health records help alert physicians to potentially inappropriate prescriptions and suggest safer alternatives," he told MedPage Today.

A previous analysis demonstrated that 13.9% of older adults with dementia had overlapping prescriptions that met criteria for CNS-active polypharmacy. More recently, data showed that new prescriptions for two classes of CNS-active drugs -- benzodiazepines and antipsychotics -- were associated with higher mortality risks for some dementia patients.

Mafi and colleagues studied prescribing patterns for CNS-active medications, focusing on potentially inappropriate drugs that should be avoided because harms outweigh expected benefits in older adults, according to the AGS Beers Criteria.

The study included five classes of CNS-active drugs: antidepressants with strong anticholinergic profiles, antipsychotics, barbiturates, benzodiazepines, and nonbenzodiazepine hypnotics.

The researchers used survey data from the Health and Retirement Study linked to Medicare fee-for-service claims to track prescribing patterns for 4,842 participants from 2013 through 2021.

During that period, benzodiazepine prescriptions declined from 11.4% to 9.1% (P=0.02) and nonbenzodiazepine hypnotic drug prescriptions fell from 7.4% to 2.9% (P<0.001). There was no significant difference in 2013 and 2021 prescribing rates for antipsychotics, antidepressants, or barbiturates.

Clinically justified prescriptions fell from 6% in 2013 to 5.5% in 2021, but the shift wasn't significant (P=0.56). Potentially inappropriate prescriptions without clinical indications declined from 15.7% to 11.4% in the same period, a statistically significant difference (P<0.001).

While CNS-active prescriptions may be appropriate in some cases, it's important for patients and caregivers to work closely with physicians to ensure these medications are right for them, said co-author Annie Yang, MD, of Yale School of Medicine in New Haven, Connecticut.

In some cases, clinicians consider whether it might be safe to taper or stop a CNS-active medication. One resource that may help is deprescribing.org, Yang noted. "This website provides a nice list of evidence-based educational materials for both clinicians and patients on how to safely reduce or stop unnecessary medications," she told MedPage Today.

The findings have limitations, Mafi and co-authors acknowledged. Medicare Advantage plan data were not included in the study, and the focus of the analysis was on prescribing prevalence, not cumulative exposure.

Disclosures

This study was supported by the National Institute on Aging (NIA) at the NIH.

Mafi reported relationships with the NIA, the Commonwealth Fund, Arnold Ventures, and the Agency for Healthcare Research and Quality.

Yang had no disclosures.

Co-authors reported relationships with several government agencies, pharmaceutical companies, and other groups.

Primary Source

JAMA

Source Reference: Yang AW, et al "Prescribing patterns of potentially inappropriate CNS-active medications in older adults" JAMA 2026; DOI: 10.1001/jama.2025.23697.

https://www.medpagetoday.com/neurology/dementia/119452