Dementia medications: knowing when to stop

The incidence of dementia has shown a downward trend in the past few decades due to improved public health campaigns, social changes resulting in less cigarette smoking, and earlier detection and treatment for risks of dementia, such as identifying and treating hypertension.1,2 However, with a growing demographic of individuals 80 years of age and older, dementia is a condition that affects many individuals. The Alzheimer Society of Canada estimates that there are more than 770,000 Canadians living with dementia in 2025.3Dementia is a broad term that includes a number of disease processes, with Alzheimer disease being the most common. This progressive condition, which affects cognition, function and behaviour, currently has no cure.Dementia treatmentsHealth Canada has been reviewing applications for disease-modifying treatments since 2024; some of these biologics or disease-modifying treatments have been available in the United States since 2023. Since 1997, symptomatic treatments have been available, with three cholinesterase inhibitors (donepezil, galantamine and rivastigmine) labelled for use in Canada. Because of the progressive nature of dementia, patients continue to decline, but cholinesterase inhibitors have some stabilizing effect on cognitive measures equating to less than one year of disease stabilization, a modest improvement in function, and marginal evidence regarding improved behaviours.4,5 However, these are averages; some patients show no benefit at all, while others show clinically noticeable improvement. In 2020, cholinesterase inhibitors accounted for more than CAN$20 million in public drug funding across the country.6Memantine is a much older medication, but less frequently used, as it is labelled for use in moderate to severe disease,7 while cholinesterase inhibitors are Health Canada-approved for use in mild/moderate (rivastigmine, galantamine) or mild/moderate/severe (donepezil) dementia.8-10 Memantine has small but statistically significant benefits in cognition, global ratings, activities of daily living, behaviour and mood, although agitation does not improve.11Medication safetyOf all symptomatic medications, memantine is the best tolerated, with some patients reporting headaches, and there is a small risk for seizures.4 Harms from cholinesterase inhibitors include bradycardia and syncope,12 as well as gastrointestinal complications that can range from mild nausea to anorexia and weight loss.13 Additional side effects of cholinesterase inhibitors include urinary urgency and bronchospasm (particularly in patients with asthma).Deprescribing guidelinesGuidelines for deprescribing these symptomatic medications have been published.14 These guidelines, prepared in collaboration with the Bruyère Institute (Ottawa), have been endorsed by a number of organizations internationally. They include an extensive evidence-based report, an algorithm with stepwise guidance, and recommendations.The guidelines recommend beginning discussions about deprescribing after a patient has been on medication for 12 months. That provides adequate time to titrate the medication to the maximum effective dose, assess tolerance and measure whether outcomes are stabilized or if further decline is taking place.As the disease progresses, the risk/benefit considerations may change as pill burden might increase, life expectancy decrease, frailty emerge, and tolerance to side effects might become unmanageable. Some patients may be tolerating the medication well and have a clinically meaningful response in function or cognition, and can be maintained on the medication if tolerated.A stepwise approach for deprescribing memantine and cholinesterase inhibitors is recommended in the guidelines due to some evidence that abrupt discontinuation can cause worsening symptoms of dementia, although there is no evidence that one tapering regimen is preferred over another. In patients who are stable (i.e., do not have current psychotic symptoms or agitation) deprescribing can be initiated. The current recommendations are to halve the dose every four weeks until the lowest available dose is used, then discontinue. Monitoring cognition, function and behaviours (neuropsychiatric symptoms) should occur every four weeks during the deprescribing process.Considerations in deprescribingPersons with dementia can be quite vulnerable. Caregivers and family members may advocate for treatment and may also be impacted by the condition and behaviours exhibited. They may feel as if they are being abandoned if medications are withdrawn. They may also observe some decline or be impacted by behaviours if the medications are discontinued. Their engagement is critical if medications are to be reviewed and deprescribing discussed. Reassurance—by using the term “trial” deprescribing—can be integrated into the discussion.A decline after removal of the medication could manifest as more apparent cognitive or functional decline, or emergence of neuropsychiatric behaviours. If the symptoms are severe and occur within the first week, the guidelines support moving back to the original dose that was used prior to deprescribing. If the symptoms start within two to six weeks, this may be re-emergence of the dementia symptoms and the previous dose can be restarted instead of continuing a reduction. If the symptoms occur at six weeks or later, it is likely emergence of symptoms of dementia and the cholinesterase inhibitor or memantine can continue to be tapered. As with any behavioural issues in dementia, proactive education is important to ensure that caregivers are aware of nonpharmacologic approaches (e.g., environmental changes, redirection, music). If behaviours emerge that are potentially harmful to the patient and/or caregivers then pharmacologic options, such as selected antidepressants or antipsychotics may be trialed.15 This may be part of the progression of the disease, but adds burden to the family and caregivers.SummaryAs cholinesterase inhibitors and memantine are not disease-modifying, have only modest effect, and are associated with some harm in older adults, we have an obligation to include deprescribing discussions at regular intervals in our care for these patients. Deprescribing guidance is available to support patients and clinicians who decide to remove these medications when they may be providing no benefit but are causing harm through adverse events and medication burden.Cheryl A Sadowski is a professor at the Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, a clinical pharmacist at the Geriatric Outpatient Clinic at the Misericordia Community Hospital in Edmonton, AB, and a member of the Canadian Medication Appropriateness and Deprescribing Network.References:Wu YT, Beiser AS, Breteler MMB, et al. The changing prevalence and incidence of dementia over time - current evidence. Nat Rev Neurol 2017;13(6):327-39.Satizabal CL, Beiser AS, Chouraki V, et al. Incidence of dementia over three decades in the Framingham Heart Study. N Engl J Med 2016;374(6):523-32.Alzheimer Society Canada. Dementia numbers in Canada. (accessed June 3, 2025).Dou K-X, Tan M-S, Tan C-C, et al. 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