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Study Confirms What Many Suspect
Wide-Ranging Polypharmacy Practices Among Elderly with Dementia

Article In Brief

New research on over one million seniors with dementia shows that many are being prescribed multiple central nervous system and neurologically-active drugs, with little evidence that these prescriptions are needed or whether or not they might interact with other drugs. Experts say the results confirm what they see in clinical practice and that this approach deserves closer scrutiny.

A review of prescription drug claims for more than one million seniors diagnosed with dementia has revealed that many are being prescribed multiple central nervous system (CNS) and neurologically-active drugs, with little evidence that these medications are needed or whether or not they might interact with each other or other drugs they are being prescribed.

Donovan T. Maust, MD, MS, an associate professor of psychiatry at the University of Michigan in Ann Arbor, and colleagues, analyzed Medicare records for 1,159,968 elderly persons with a documented history of dementia living outside of care facilities, and found that nearly 14 percent were being prescribed three or more medications from these drug classes—antidepressants, antipsychotics,anti-seizure drugs, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, and opioids—or 30 days or more.

“Community-dwelling older adults with dementia have a high prevalence of psychotropic and opioid use. In these patients, CNS–active polypharmacy may increase the risk for impaired cognition, fall-related injury, and death,” said Dr. Maust, adding that that is why the investigators undertook the review.

“I think probably some of us thought this amount of prescribing might be going on, but there weren't really prior studies specifically looking at polypharmacy to set expectations. Unfortunately, I was not especially surprised—the findings confirmed what I was worried about,” he told Neurology Today.

Dementia experts who were not involved with the study agreed that the findings confirmed what they saw in clinical practice, adding that the practice deserves closer scrutiny.

Study Findings

In the current study, the median number of polypharmacy-days for those who met the criterion for CNS-active polypharmacy was 193. Among these patients, 57.8 percent were exposed for longer than 180 days, and 6.8 percent were exposed for 365 days. Moreover, 29.4 percent were exposed to five or more medications, and 5.2 percent were exposed to five or more medication classes.

Ninety-two percent of polypharmacy-days included an antidepressant, 47.1 percent included an antipsychotic, and 40.7 percent included a benzodiazepine. The most common medication class combination included an antidepressant, an anti-seizure drug, and an antipsychotic (12.9 percent of days). Gabapentin was the most common medication and was associated with 33.0 percent of all polypharmacy-days.

Dr. Maust said he was surprised at how many patients were being prescribed gabapentin and how many people were taking combinations that included benzodiazepines.

“We have known that gabapentin use among older adults is increasing... I suspect that a large amount of it is probably for pain and possibly anxiety. Given the longstanding concerns about benzo-prescribing for older adults and their known impact on cognition, it was also surprising to see how much benzo prescribing there was,” he told Neurology Today.

Among the risks facing these patients, he said, are potential drug-drug interactions.” This is particularly true when you think about all of the other medications these older adults are likely being prescribed for their other medical conditions,” Dr. Maust said.


“Also, remember, almost everything in dementia medication is used off-label and is either ungoverned or governed by primitive guidelines, so this is an area in need of greater scrutiny.”—DR. MARWAN SABBAGH

“Most of these medications are now available as generic medications, so I am unaware of companies looking at these particular medications for future additional indications. We did not look at the dose of medication prescribed in this analysis. Generally, the risk of potential harm increases with the dose. For example, the risk of falls is higher as the benzo dose goes up, so generally, clinicians should aim for the lowest effective dose if the medication is absolutely necessary,” he told Neurology Today.

Unfortunately, outside of clinical trials or some research cohort studies, there are few good data sources that provide a window onto behavioral symptoms in these patients, he noted. Clinicians may be doing some brief psychological testing as part of the Medicare Annual Wellness Visit. “For these patients—who a clinician has indicated has dementia in a Medicare patient encounter—I would hope that some sort of regular cognitive testing is happening, though there is no way to know that from the claims data.”

One question is who is in charge of administering these medications. The first thing to note is the analysis did not include patients in nursing homes.

“In most cases, these older adults would have a caregiver with them at health care visits, but certainly not all of them would. Like with any type of health care or prescribing, someone must perceive a problem going on, and the prescription is the response. Some are probably initiated by the clinician, some by the patient, and others by caregivers. I would hope that symptom response is regularly assessed, but the natural history of these behavioral symptoms is to ‘wax and wane,’ so in many cases, these symptoms would probably improve regardless of whether a medication was started.

However, the lack of information on prescribing indications limits judgments about the medical appropriateness of medication combinations for individual patients, the authors stated.

Expert Commentary

Marwan Sabbagh, MD, director of the Cleveland Clinic's Lou Ruvo Center for Brain Health, said that while the rate of polypharmacy for 30 days, at 13.9 percent, might not at first seem excessive if you multiply that by the number of patients—more than 32,000—by 365 days, you're dealing with around four million polypharmacy days a year.

“Also, remember, almost everything in dementia medication is used off-label and is either ungoverned or governed by primitive guidelines, so this is an area in need of greater scrutiny,” he said.

“I think that behind the scenes, there's a lack of authority. I don't think that many people are aware of this issue, and these patients often have three or four different doctors [involved in their care.]”

Also, he said that numbers alone do not necessarily paint a clear picture of polypharmacy in dementia care, nor do they reflect or suggest any trends upwards or downwards in prescribing patterns for such patients.

Maria Kataki, MD, PhD, FAAN, associate professor of clinical neurology in the Cognitive and Memory Disorders Center at Ohio State University (OSU), in Columbus, told Neurology Today that the findings reflect her clinical experience.

“I am not surprised at all because I see those issues when I evaluate elderly patients with cognitive symptoms in my practice,” she said.

“I always list medication side effects as possible contributors to the cognitive issues or worsening behaviors,” she continued. “If so, I evaluate the possibility of weaning [a patient] off of some of the medications if possible or communicating with the prescribing physician to alter the medications in question.”

She said that she first recommends that these patients be evaluated by dementia experts; board-certified neurologists with subspecialty training in Alzheimer's disease and dementia, cognitive neurology, neuropsychiatry, neurobehavioral neurology, where during a comprehensive neurological, cognitive, and functional assessment, issues of polypharmacy could be addressed appropriately.

“That, of course, indicates that the primary care doctor will screen the elderly patients for cognitive and functional decline early on and will refer them to a cognitive neurologist for further evaluation and management. If that procedure takes place early on and patients are appropriately diagnosed and treated based on neurologic indication, the chance of polypharmacy could be minimized,” Dr. Kataki said.

Asked if the data suggest that many of these elderly dementia patients are simply being placed in a so-called prescription ‘straitjacket,’ Dr. Kataki said there are several other parameters that should be evaluated before drawing any conclusions. Study limitations are listed that make it very obvious that we should have future longitudinal prospective studies, she said. “These include those by and at university centers, focusing on accurate diagnosis, diagnostic indications of prescribing medications, and the impact of prescribing medications in the patient's and caregiver's quality of life, wellbeing, and survival.

At the Cognitive and Memory Disorders Center at the OSU, regarding patients that are evaluated for cognitive issues, [we] inquire about the caregiver responsible for the patient's care, Dr. Kataki continued.

“In the case of a patient that is placed in a nursing home, we gather information from nursing staff and at times health care providers that manage the patients in the facility in addition to the observations of the family. It is a complex process, and communication with all parties might identify behavioral triggers, appropriate non-pharmacological interventions and appropriate plans of care in case of pharmacological management.”


Dr. Maust reported no disclosures. Drs. Kataki and Sabbagh reported no disclosures.

Link Up for More Information

• Maust DT, Strominger J, Kim HM, et al. Prevalence of central nervous system-active polypharmacy among older adults with dementia in the US JAMA 2021;325(10):952–961. DOI: 10.1001/jama.2021.1195.
• American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers Criteria for potentially inappropriate medication use in older adults J Am Geriatr Soc 2015;63(11):2227–2246.
    • US Food and Drug Administration. FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. Published August 31, 2016. Accessed March 10, 2021.