Observational study finds one in four older adults with dementia prescribed CNS-active medications — Evidence Review
Published in JAMA, by researchers from David Geffen School of Medicine at UCLA, RAND, University of Michigan
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Table of Contents
About one in four older Americans with dementia are prescribed potentially risky brain-altering medications, despite longstanding safety concerns, according to a new study; related research generally supports these findings and highlights persistent issues with inappropriate prescribing and elevated risk of adverse outcomes. The study from the David Geffen School of Medicine at UCLA aligns with prior evidence linking these medications to increased risks of falls, confusion, and hospitalization in people with cognitive impairment.
- Multiple studies confirm that antidepressants, antipsychotics, and anti-anxiety medications are associated with increased risks of falls and mortality in older adults with dementia, supporting concerns about the safety of these prescriptions 2 3 6 7 8 10.
- While some research suggests overall prescribing rates for certain CNS-active drugs are declining, the prevalence of potentially inappropriate or harmful prescribing remains high, especially among individuals with cognitive impairment 12 13 15.
- There is broad consensus in the literature that alternative, non-pharmacological interventions should be prioritized and that medication use should be regularly reviewed to minimize harm in this vulnerable population 9 10.
Study Overview and Key Findings
Despite longstanding cautions in medical guidelines, central nervous system (CNS)-active medications—which can increase the risk of falls, confusion, and hospitalizations—continue to be widely prescribed to older adults with dementia. This study is significant as it provides up-to-date national data on prescribing patterns among Medicare beneficiaries from 2013 to 2021, highlighting not only trends over time but also the persistent gap between recommended best practices and real-world clinical care. The findings underscore ongoing challenges in optimizing medication safety for cognitively impaired older adults, particularly given the high proportion of prescriptions without clear clinical indications.
| Property | Value |
|---|---|
| Study Year | 2023 |
| Organization | David Geffen School of Medicine at UCLA, RAND, University of Michigan |
| Journal Name | JAMA |
| Authors | Dr. John N. Mafi, Mei Leng, Dr. Dan Ly, Chi-Hong Tseng, Dr. Catherine Sarkisian, Nina Harawa, Cheryl Damberg, Dr. A. Mark Fendrick |
| Population | Older adults with dementia and cognitive impairment |
| Methods | Observational Study |
| Outcome | Prescribing patterns of CNS-active medications |
| Results | About one in four Medicare beneficiaries with dementia receive these drugs. |
Literature Review: Related Studies
To place these findings in context, we searched the Consensus paper database, which contains over 200 million research papers. The following queries were used to identify relevant studies:
- dementia medication falls risk
- antipsychotics dementia patient outcomes
- prescription patterns dementia Medicare beneficiaries
Literature Review Table
| Topic | Key Findings |
|---|---|
| What is the risk of falls and other adverse outcomes from CNS-active medications in older adults with dementia? | - Use of multiple psychoactive drugs, antidepressants, and anti-anxiety drugs strongly increases fall risk in nursing home residents with dementia 2 3 5. - Certain CNS-active medications, including cholinesterase inhibitors and antipsychotics, are linked to syncope, fractures, and increased mortality in this population 1 5 6 7 8 10. |
| How do prescribing patterns and appropriateness of CNS-active medications vary among older adults with cognitive impairment? | - Rates of potentially inappropriate prescribing remain high among older adults with dementia, with significant regional and demographic disparities 12 13 15. - Antipsychotic and psychotropic medication use is influenced by provider specialty, geography, and patient characteristics 11 12 13 15. |
| What are the comparative risks and benefits of different CNS-active drugs used to treat behavioral symptoms in dementia? | - Antipsychotics offer modest benefits for behavioral symptoms but carry serious safety risks, including increased mortality; no single agent is clearly safest or most effective 7 8 9 10. - Some antidepressants and anxiolytics are associated with increased fall risk; benzodiazepines may paradoxically be associated with reduced falls in some cohorts 4 5. |
What is the risk of falls and other adverse outcomes from CNS-active medications in older adults with dementia?
Numerous studies have documented that older adults with dementia are at increased risk for falls, syncope, fractures, and mortality when prescribed CNS-active medications, particularly psychoactive agents such as antidepressants, antipsychotics, and anti-anxiety drugs. The new study’s finding that these drugs remain commonly prescribed, despite known risks, is consistent with a substantial body of evidence highlighting the vulnerability of this population to medication-related harm.
- Strong evidence links the use of multiple psychoactive drugs, antidepressants, and anti-anxiety medications to a higher risk of falls in nursing home and community-dwelling older adults with dementia 2 3 5.
- Cholinesterase inhibitors may increase the risk of syncope, while memantine may reduce fracture risk but does not alter fall risk 1.
- Antipsychotic use is associated with a higher risk of death in older adults with dementia, especially with conventional agents and higher doses 6 7 8 10.
- Selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and other psychotropic medications also contribute to increased fall risk 4 5.
How do prescribing patterns and appropriateness of CNS-active medications vary among older adults with cognitive impairment?
The new study’s report of persistent high rates of potentially inappropriate CNS-active medication prescribing aligns with prior research showing considerable variation in prescription patterns and ongoing quality concerns. Disparities exist by geography, race/ethnicity, provider specialty, and patient demographics, and inappropriate or unnecessary prescribing remains a significant issue.
- Prescribing rates for antipsychotics and other CNS-active medications among dementia patients are influenced by factors including age, dual eligibility, comorbidities, and regional practice patterns 12 13 15.
- Inappropriate concurrent use of acetylcholinesterase inhibitors and anticholinergic medications is common, exposing patients to additional risk 12.
- Antidementia drug use is relatively low overall, with substantial disparities by race/ethnicity and timing of initiation relative to diagnosis 13.
- Provider specialty plays a role: patients seeing psychiatrists or neurologists are more likely to receive CNS-active prescriptions compared to those managed by primary care providers 11.
What are the comparative risks and benefits of different CNS-active drugs used to treat behavioral symptoms in dementia?
While antipsychotics and other CNS-active drugs are sometimes used to manage behavioral and psychological symptoms of dementia, studies consistently show only modest effectiveness with significant safety trade-offs. The literature underscores the lack of a single best agent and the need for individualized risk-benefit assessments.
- Antipsychotics are associated with increased mortality in older adults with dementia, with the risk varying by agent and dose, but no single antipsychotic emerges as both highly effective and low-risk 7 8 9 10.
- Aripiprazole may be relatively safer, but all atypical antipsychotics carry boxed warnings for increased mortality and cerebrovascular risk 9.
- Some studies suggest benzodiazepines may be associated with decreased falls in certain populations, though overall psychotropic medication use is linked to higher fall risk 4 5.
- The evidence supports prioritizing non-pharmacological approaches to managing behavioral symptoms and minimizing exposure to CNS-active drugs whenever feasible 9 10.
Future Research Questions
While current evidence highlights key risks and prescribing challenges, further research is needed to address gaps identified by the new study and the broader literature. Areas warranting investigation include strategies to reduce inappropriate prescribing, individualized risk assessment, and the impact of deprescribing interventions.
| Research Question | Relevance |
|---|---|
| What are the most effective interventions to reduce inappropriate CNS-active medication prescribing in older adults with dementia? | Identifying evidence-based strategies to minimize potentially harmful or unnecessary prescriptions could improve patient safety and outcomes 9 10 12. |
| How does deprescribing CNS-active medications affect fall, hospitalization, and mortality rates in people with dementia? | There is limited evidence on the clinical outcomes of deprescribing interventions, particularly in frail, cognitively impaired populations 14. |
| What patient and provider factors predict persistent inappropriate CNS-active medication use in dementia? | Understanding the drivers of inappropriate prescribing can inform targeted interventions and policies to reduce unnecessary exposure 11 12 13 15. |
| How do non-pharmacological interventions compare with pharmacological treatments for behavioral symptoms in dementia? | Evidence suggests non-drug approaches may be safer, but comparative effectiveness studies are needed to guide clinical decision-making 9 10. |
| What are the long-term effects of chronic CNS-active medication use in older adults with mild cognitive impairment? | Little is known about the progression of risks and benefits associated with sustained use of these medications in individuals with milder cognitive deficits 5. |
This article summarizes the current state of evidence on CNS-active medication prescribing in older adults with dementia, highlighting persistent safety concerns and the need for targeted strategies to improve prescribing practices and patient outcomes.