This prospective study demonstrates that daily medications for chronic conditions are commonly and persistently prescribed to NH residents with advanced dementia. Although some medications of questionable benefit were discontinued towards the end-of-life (e.g., anti-dementia drugs), reductions often occurred only when death was imminent, and some drugs with unclear benefits (e.g. lipid-lowering agents) or potential harmful side effects (e.g., antipsychotics) did not decline. In addition, although the stated primary goal of care was comfort for 90% of residents, up to 40% were prescribed drugs deemed “inappropriate” in end-stage dementia when palliation is the goal of care. These findings raise concerns not only about the burden of medication use in advanced dementia, but also about how decisions regarding drug treatment are made for these residents.
This study supports previous work demonstrating that the on-going use of daily medications to treat chronic conditions is common among terminally ill patients, and extends these findings to NH residents with end-stage dementia. Our cohort took an average of 6 daily medications, which is comparable to the general NH population (mean, 7-8),4
and at the lower range reported for patients with terminal conditions (6.5 to 14.6).10, 15, 16
Blass et al. reported that NH residents with advanced dementia took a mean of 15 daily medications, but that study’s medication inclusion criteria were broader (e.g., measured all medications, including antimicrobials and as needed medications). Our study further corroborates that the total number of daily medications remains unchanged as residents with advanced dementia approach death, and mirrors previously reported shifts away from medications for comorbid medical conditions (e.g. osteoporosis) toward palliative and symptom-specific medications (e.g., opioids, scopolamine).10, 15
The determination that a drug is unambiguously inappropriate in advanced dementia is hampered by limited outcome data and variability in individual patient preferences. Despite these challenges, a recent expert panel concluded that a small number of medications are “never appropriate” in advanced dementia when the primary goal of care is palliation.16
In a cross-sectional examination of 34 NH residents with advanced dementia, the panel reported that 29% were prescribed at least one of these drugs.16
In this much larger prospective cohort, almost 40% of residents were prescribed at least one “never appropriate” medication over 18 months, and 18% remained on these drugs at death. Anti-dementia and lipid-lowering agents were the most common “never appropriate” medications. Although acetylcholinesterase inhibitors were approved for the treatment of severe dementia after the consensus panel established the “never appropriate” list, and limited evidence suggests that anti-dementia drugs may improve outcomes in moderate dementia,25
to date there still remains a lack of convincing data to support on-going use in end-stage disease. Continued lipid-lowering treatment is hard to justify in end-stage dementia patients when comfort is the goal of care, as the sequelae of hyperlipidemia are no longer relevant.
Two drugs not on the “never appropriate” list warrant further comment. First, antipsychotics were taken by almost one-third of residents and did not diminish as death approached. Several studies, including a randomized trial26
, fail to support the off-label use of antipsychotics to treat behavior problems in dementia. Moreover, these drugs have serious adverse sequelae in dementia patients, including extrapyramidalism and increased mortality.27
Second, proton pump inhibitors were taken by one-fifth of residents and did not diminish as death approached. Although PPIs are often used for gastrointestinal prophylaxis in NSAID users, PPI use far exceeded NSAID use in our study. As one of the most frequently prescribed classes of drugs in the world, PPIs are well-known to be over-prescribed.28
Often initiated during hospitalization and continued upon discharge without clear indication29
, PPIs are prime candidates for reconsideration in NH residents with advanced dementia, particularly upon return from the hospital.
Our findings suggest some factors may help identify NH residents with advanced dementia who are at higher risk for greater medication burden. Male residents were at increased risk for both being on inappropriate and a greater number of daily medications. The fact that a recent acute illness was associated with taking more medications may reflect the addition of new drugs necessary to treat that episode. The variable capturing recent acute illness was also collinear with recent hospitalization. Taken together, our findings suggest that acute illnesses and healthcare transitions may lead to the initiation of medications that are not indicated in advanced dementia on an ongoing basis, and highlights the need for careful medication review following such events. The fact that residents with DNH orders were less likely to be on an inappropriate medication further suggests that advance care planning which directs care toward comfort may be an important step in reducing inappropriate medication use in advanced dementia. The finding that residents referred to hospice took more daily medications does not necessarily contradict this notion, as a shift towards palliation may require the addition of new drugs appropriately needed for symptom control (e.g., opioids and scopolamine).
It is important to consider our findings in light of the study’s limitations. First, the study population was drawn from NHs in the Boston area and the cohort was predominately white, thus potentially limiting the generalizability of our findings. Second, while NH characteristics may influence end of life care, this study was not designed and lacks adequate power to identify NH factors influencing prescribing patterns at the facility level.
Finally, the “never appropriate” categorization by Holmes et al16
remains subject to interpretation and a more rigorous consensus process should be pursued as a next step towards establishing physician prescribing guidelines for advanced dementia.
To date, this is the largest study of daily medication use in advanced dementia. Our findings indicate that many NH residents with this condition receive drug treatment that is no longer appropriate given their advanced disability and limited life expectancy. The burden, costs and risks of polypharmacy are considerable, particularly in this frail population. Our results underscore the need for shared decision-making between providers and families of patients with end-stage dementia, in order to ascertain the goal of care, review the advantages and disadvantages of each ongoing medication, and to align treatment with stated preferences. When palliation is identified as the goal of care, the use of medications of questionable benefit should be reconsidered in favor of treatment that promotes comfort.