Given the behavioral issues associated with dementia, there is widespread use of central nervous system (CNS)-active medications in such patients. CNS-active medications (also referred to as psychotropic or psychoactive drugs) are those drugs with potent activity in the human brain and include the following major therapeutic classes: antidepressants, antipsychotics, antiepileptics (drugs for seizures), benzodiazepine tranquilizers, nonbenzodiazepine insomnia drugs (often called Z-drugs) and...
Given the behavioral issues associated with dementia, there is widespread use of central nervous system (CNS)-active medications in such patients. CNS-active medications (also referred to as psychotropic or psychoactive drugs) are those drugs with potent activity in the human brain and include the following major therapeutic classes: antidepressants, antipsychotics, antiepileptics (drugs for seizures), benzodiazepine tranquilizers, nonbenzodiazepine insomnia drugs (often called Z-drugs) and opioids.
Research published in the March 9, 2021, issue of the Journal of the American Medical Association (JAMA) quantified the simultaneous use of multiple CNS-active drugs among older patients with dementia in the U.S. The researchers found marked overuse of CNS-active drugs in these patients despite the substantial risks, including premature death.
Background on dementia
Dementia often results in devastating reductions in cognition (the ability to think, remember and reason) that interfere with language, perception, problem-solving, attention, emotional regulation and maintenance of personality. The disorder ranges in severity from mild to severe, the latter of which may require people to be completely dependent on others for their basic daily activities (for example, eating, bathing and toileting).
Although up to half of all people older than 85 years may have some degree of dementia, the disease is not an inevitable part of aging, as many people live into their 90s and beyond without any signs of such illness.
Alzheimer’s disease is the most common cause of dementia in the U.S., afflicting more than six million people, most of whom are over age 65. A hallmark of Alzheimer’s disease is abnormal deposits of a protein called amyloid-beta in the brain. Other types of dementia include the following:
- Lewy body dementia (characterized by abnormal deposits of another protein, alpha-synuclein, in the brain)
- Frontotemporal disorders (results from damage to nerve cells in the parts of the brain known as the frontal and temporal lobes, which play key roles in thinking, language and memory)
- Vascular dementia (caused by strokes and other disorders that result in decreased blood flow to the brain)
CNS-active polypharmacy study
For the new JAMA study, researchers used Medicare claims data to identify all patients in the U.S. enrolled continuously in traditional fee-for-service Medicare from 2015 to 2017 who had been diagnosed with dementia and were not nursing-home residents. Nearly 1.2 million patients met these criteria and were included in the study. For half of the patients, the type of dementia was not specified, 40% had Alzheimer’s disease and 15% had vascular dementia (some patients had more than one type of dementia diagnosis).
The researchers determined the proportion of these patients who had CNS-active polypharmacy in 2018, defined as having filled prescriptions simultaneously for three or more different CNS-active medications for longer than 30 consecutive days anytime during that year.
Notably, the American Geriatrics Society advises against CNS-active polypharmacy in elderly patients because it is associated with an increased risk of falling. Combined use of CNS-active medications also is associated with cognitive decline in older adults, as well as impaired breathing and death when opioids are involved.
CNS-active polypharmacy was found in 161,412 (14%) of the dementia patients. These cases corresponded to over one million person-months of CNS-active polypharmacy exposure. Among those exposed to CNS-active polypharmacy, 58% were exposed for longer than six months and 7% for an entire year, and 29% were exposed to five or more medications.
Antidepressants were found in 92% of the CNS-active polypharmacy-days, antiepileptics 62%, antipsychotics 47%, benzodiazepines 41%, opioids 32% and Z-drugs 6%. The antiepileptic gabapentin (GRALISE, HORIZANT, NEURONTIN) was the most common CNS-active medication prescribed, accounting for 33% of all polypharmacy-days. The next two most commonly prescribed CNS-active drugs were the antidepressant trazodone (generic only) and the antipsychotic quetiapine (SEROQUEL), accounting for 26% and 24% of polypharmacy-days, respectively.
Public Citizen’s Health Research Group has designated gabapentin and quetiapine as Limited Use,, and trazodone is classified as Do Not Use because safer antidepressants are available. Quetiapine is one of many antipsychotics that carry the following black-box warning, the strongest warning required by the FDA, in the product labeling:
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. SEROQUEL is not approved for elderly patients with dementia-related psychosis.
In discussing their results, the JAMA researchers appropriately noted that there is “minimal high-quality evidence” that antidepressants are efficacious in treating depression in patients with dementia. They further stated that trazodone often is used for insomnia, gabapentin for psychiatric and certain pain disorders, and quetiapine for anxiety or insomnia — all uses that are suspect because they are not FDA-approved (so-called “off-label” uses).
What You Can Do
If you have dementia or are the primary caregiver for a loved one with dementia, carefully monitor your or your loved one’s prescribed medications. Make sure that all involved physicians (elderly people often see several) have a complete list of drugs you or your loved one is taking. Be sure that any CNS-active medication has been prescribed for an FDA-approved use and avoid using more than one CNS-active drug at a time.
Never taper or discontinue any CNS-active drug without first talking to the prescribing doctor or health care professional.
 National Institutes of Health, National Institute on Aging. Basics of Alzheimer’s disease and dementia. What is dementia? Symptoms, types, and diagnosis. December 31, 2017. https://www.nia.nih.gov/health/what-dementia-symptoms-types-and-diagnosis. Accessed June 28, 2021.
 National Institutes of Health, National Institute on Aging. Alzheimer's disease fact sheet. May 22, 2019. https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet. Accessed June 28, 2021.
 National Institutes of Health, National Institute on Aging. Related dementias: What Is Lewy body dementia? June 27, 2018. https://www.nia.nih.gov/health/what-lewy-body-dementia. Accessed June 28, 2021.
 National Institutes of Health, National Institute on Aging. Related dementias: What are frontotemporal disorders? March 29, 2019. https://www.nia.nih.gov/health/what-are-frontotemporal-disorders. Accessed June 28, 2021.
 National Institutes of Health, National Institute on Aging. Related dementias: Vascular contributions to cognitive impairment and dementia. December 31, 2017. https://www.nia.nih.gov/health/vascular-contributions-cognitive-impairment-and-dementia. Accessed June 28, 2021.
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 Gabapentinoid drug use is exploding despite poor safety and efficacy profiles. Worst Pills, Best Pills News. October 2020. https://www.worstpills.org/newsletters/view/1358. Accessed June 28, 2021.
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