Experts agree that reducing some medications may improve the quality of life for patients with advanced dementia by eliminating side effects and the discomfort of swallowing unneeded pills. Despite this, overmedication remains a significant problem, according to a paper in the September 8 JAMA Internal Medicine. In the first large nationwide study to examine this issue, researchers led by Jennifer Tjia at the University of Massachusetts Medical School, Worcester, analyzed data from thousands of patients with severe dementia. They found that more than half received at least one medication of questionable benefit. These potentially unnecessary prescriptions place burdens on patients and staff, and cost insurers almost $300 per patient per month, the authors report.

“Reviewing medication lists and stopping nonbeneficial drug use should be a top priority for prescribers,” wrote Greg Sachs, a geriatrician at Eskenazi Health, Indianapolis, Indiana, in an accompanying JAMA commentary. He sat on a panel of geriatricians that identified medications of dubious benefit for advanced dementia patients (see Holmes et al., 2006; Holmes et al., 2008). That list includes acetylcholinesterase inhibitors and the NMDA receptor antagonist memantine, the only drugs specifically approved for AD in the United States. Some Alzheimer’s clinicians who spoke with Alzforum questioned the inclusion of these drugs on that list.

Most previous studies of prescription drug use in late dementia were small or focused on only one type of medication (see Currow et al., 2007; Blass et al., 2008; Weschules et al., 2008; Tjia et al., 2010). To gain a broader view, Tjia and colleagues reviewed three month’s worth of 2009 data from a pharmacy that serves about half the nursing home residents in the United States. The authors limited the analysis to 5,400 patients who had severe dementia, defined as a Mini-Mental State Examination score of five or less. Most of these patients were bedridden, could not speak more than a few words, and were expected to live only one or two more years. The authors used the list generated by Sachs and his colleagues to judge whether medications were unnecessary.

Among this group of patients, more than a third received a cholinesterase inhibitor, while a quarter took memantine. Medications for cardiovascular disease were also common, with 22 percent taking a lipid-lowering drug, such as statins, and 7 percent taking an anticlotting agent other than aspirin, such as the antiplatelet drug clopidrogel (Plavix). These latter two drug classes are considered unnecessary for patients with such advanced disease because they aim to reduce the risk of future cardiac problems. Participants in this study rarely used any other medication of questionable benefit. A total of 54 percent of patients with severe AD took at least one questionable medication, which accounted for about one-third of the total cost of their prescriptions.

Several factors affected a patient’s likelihood of being on these medications, the authors found. Patients who were older, had trouble with daily activities such as feeding themselves, had problems swallowing, or behaved aggressively were less likely to take these drugs, perhaps reflecting the difficulty of administering pills. Patients in hospice care and those who had a Do Not Resuscitate order were also less likely to receive these drugs, suggesting that physicians take into account the level of medical intervention the family desires. On the other hand, patients who were recently hospitalized, or had a diagnosis of hypertension, diabetes, or depression, were more likely to be on them.

The authors also found differences in medication use among facilities in different parts of the country. Nursing homes in the mid-Atlantic region, for example, were least likely to have residents taking medications on this list. A similar pattern appears in other studies of medical interventions, such as feeding tubes and dialysis (see, e.g., Mitchell et al., 2003; Gessert et al., 2013), although it is unclear what underlies these regional variations, Tjia told Alzforum. Facilities that had the most residents on feeding tubes also had the most taking these drugs, suggesting that an institution’s stance on medical intervention affects prescriptions.

Tjia said the data ring true to her experience as a geriatric and palliative care physician in nursing homes, where she saw overmedication of advanced dementia patients as a significant problem, and one counter to the wishes of close relatives. Family members say the goal of medical care at the end of life should be to keep their loved ones comfortable (see Luchins et al., 1993; Mitchell et al., 2009). Unnecessary medications can cause side effects such as nausea, muscle aches, and difficulty urinating, Tjia said. These effects may not be obvious to family members, and people with late-stage AD cannot communicate their discomfort. “Side effects are underestimated,” Tjia believes. “In my clinical experience, stopping medications sometimes helps people become more alert and interactive.”

Why do physicians continue to prescribe medications, such as statins and antiplatelet drugs, for advanced dementia patients? In many cases, it is easier than stopping them, clinicians agreed. Because doctors fear that discontinuing a drug could do harm, they will let the prescription run if the patient appears to tolerate it. In addition, caregivers may find it difficult to talk about stopping medications. For family members, withdrawing prescriptions may symbolize giving up on their loved one, Tjia said. Nonetheless, doctors should schedule periodic medication reviews for advanced dementia patients and talk to families about their goals and wishes, she suggested.

Alzheimer’s clinicians agreed that drugs to lower lipids or prevent clotting probably provide little benefit to people with late-stage AD and should be stopped. However, cholinesterase inhibitors and memantine, both of which are approved for use in severe dementia, are another matter, they told Alzforum. “These medications may help a patient’s day-to-day functioning,” said Andrew Budson at the Boston University Alzheimer’s Disease Center. Several studies have reported small functional and cognitive benefits from cholinesterase inhibitors or memantine for patients with severe dementia, although the drugs do not seem to improve activities of daily living or delay nursing home admissions (see Winblad et al., 1999; Jul 2004; Apr 2006 news story; Aug 2007 news story).

Many clinicians cited the DOMINO (Donepezil and Memantine in Moderate to Severe Alzheimer’s Disease) trial as particularly influential on their thinking. In this U.K. study, researchers led by Robert Howard at King’s College London, found that advanced AD patients who discontinued donepezil declined more rapidly than those who stayed on the drug. Meanwhile, memantine had little effect on cognition, but seemed to improve behavior (see Mar 2012 news story). Patients had an MMSE of nine at the beginning of DOMINO, meaning they were initially less impaired than those in Tjia’s study, but continued to benefit from the drug over the next year, Howard told Alzforum. Howard agreed that at the most advanced stages of disease, the drugs may not help. The difficulty lies in judging where that tipping point occurs for each patient, he said. Lon Schneider at the University of Southern California, Los Angeles, thought that they may benefit only some late-stage patients. “It surely is not the case that all people whose MMSEs drop to five should be discontinued from these medications, but the use is clearly excessive,” he said.

“In severe dementia patients, there is no consensus on whether these drugs are helpful or not. Doctors often simply let the meds continue, or do whatever the family member requests,” Murali Doraiswamy at Duke University, Durham, North Carolina, wrote to Alzforum.

Family members often want their loved one to continue on dementia meds. Alzheimer’s advocate Meryl Comer, who cared for her husband with early onset AD at home throughout his illness (see Aug 2014 news story), noted that the drugs seemed to help control his symptoms. “Memantine made him more cooperative, and that made the difference between keeping him at home and being forced to institutionalize him. But there was a window [of effectiveness], and then it closed.” Comer kept her husband on Aricept for about 10 years. “I was terrified that if I stopped it, his loss of function would be more extreme,” she said.

The same dilemma occurs in other countries. In Canada, which has a single-payer healthcare system, guidelines suggest prescribing cholinesterase inhibitors only for mild to moderate AD, Nathan Herrmann at Sunnybrook Research Institute, Toronto, told Alzforum. However, many physicians continue to prescribe these drugs for patients with severe AD until death, he said. Far fewer Canadian patients take memantine, as the healthcare system does not cover it. In the United Kingdom, the National Institute for Health and Care Excellence (NICE) used to restrict cholinesterase inhibitors and memantine to mild and moderate AD. However, NICE now leaves the decision of when to discontinue these meds up to individual physicians, Howard said.

Across the board, clinicians said they wanted more data on the risks and benefits of stopping dementia meds in late-stage disease. Herrmann is wrapping up a Phase 3 study that examines the effect of withdrawing cholinesterase inhibitors from nursing home patients with severe dementia.


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News Citations

  1. Cholinesterase Inhibitors Not What They're Cracked Up To Be?
  2. Donepezil—Relief for Patients with Severe AD?
  3. Donepezil—Trial Data Show Some Benefit for Patients with Severe AD
  4. Drug Treatment Outperforms Placebo in Advanced Alzheimer's
  5. Book Review: 'Slow Dancing With a Stranger'

Paper Citations

  1. . Reconsidering medication appropriateness for patients late in life. Arch Intern Med. 2006 Mar 27;166(6):605-9. PubMed.
  2. . Integrating palliative medicine into the care of persons with advanced dementia: identifying appropriate medication use. J Am Geriatr Soc. 2008 Jul;56(7):1306-11. PubMed.
  3. . Prescribing in palliative care as death approaches. J Am Geriatr Soc. 2007 Apr;55(4):590-5. PubMed.
  4. . Medication use in nursing home residents with advanced dementia. Int J Geriatr Psychiatry. 2008 May;23(5):490-6. PubMed.
  5. . Acetylcholinesterase inhibitor and N-methyl-D-aspartic acid receptor antagonist use among hospice enrollees with a primary diagnosis of dementia. J Palliat Med. 2008 Jun;11(5):738-45. PubMed.
  6. . Daily medication use in nursing home residents with advanced dementia. J Am Geriatr Soc. 2010 May;58(5):880-8. PubMed.
  7. . Regional variation in care at the end of life: discontinuation of dialysis. BMC Geriatr. 2013 May 1;13:39. PubMed.
  8. . What is appropriate health care for end-stage dementia?. J Am Geriatr Soc. 1993 Jan;41(1):25-30. PubMed.
  9. . The clinical course of advanced dementia. N Engl J Med. 2009 Oct 15;361(16):1529-38. PubMed.
  10. . Memantine in severe dementia: results of the 9M-Best Study (Benefit and efficacy in severely demented patients during treatment with memantine). Int J Geriatr Psychiatry. 1999 Feb;14(2):135-46. PubMed.

External Citations

  1. Phase 3 study

Further Reading

Primary Papers

  1. . Use of medications of questionable benefit in advanced dementia. JAMA Intern Med. 2014 Nov;174(11):1763-71. PubMed.
  2. . Improving Prescribing Practices Late in Life: A Task for all Clinicians, Not Just Nursing Home Physicians. JAMA Intern Med. 2014 Sep 8; PubMed.