Medications, while with modest benefits, may be prescribed to relieve some symptoms and behaviour changes associated with dementia. However, ongoing debates over their effectiveness continue – the benefits and risks of the medications are discussed.
Common Medications Prescribed for Dementia
Pharmacological management of dementia should be used within a multidisciplinary biopsychosocial approach, where medical issues, behavioural and psychological symptoms, as well as the general wellbeing of the person living with dementia and caregiver, are being considered.
Acetylcholinesterase Inhibitors
Uses:
- Symptomatic management for cognition and global functioning
- Used primarily to treat mild to moderate stages of the disease although there is also evidence of effectiveness in advanced dementia
Types of drugs:
- Donepezil (Aricept)
- Rivastigmine (Exelon*)
- Galantamine (Reminyl)
Note: Exelon is available in a patch form to be stuck onto the skin.
N-methyl D-aspartate (NMDA) antagonists (which prevent cell damage from glutamate), such as Memantine
Uses:
- Used to treat moderate to advanced stages of the disease
- Little evidence supports its benefit in mild dementia
- Can be used on its own or in combination with AChEIs
Types of drugs:
- Memantine
Antipsychotics, Antidepressants, Mood Stabilisers and Sedatives
Uses:
- Used to treat various behaviour changes associated with dementia, such as anxiety, depression, aggression, agitation and sleep problems
Types of drugs:
- Typical: Haloperidol
- Atypical: Quetiapine, Risperidone, Olanzapine, etc.
The following sections provide more detailed information on each type of medication.
Acetylcholinesterase inhibitors (AChEIs)
AChEIs remain as one of the key medications for symptomatic management in persons living with dementia. To date, there is limited evidence supporting AChEIs of having effect in neuroprotection or alteration of the disease trajectory.
What It Is Used For
AChEIs has been shown to improve activities of daily living (ADLs), cognitive and neuropsychiatric symptoms in mild to moderate dementia1, as well as in severe Alzheimer’s disease.2
Three AChEIs are available in Singapore and all have demonstrated their efficacy in dementia management. Despite the slight variations in the mode of action, there is no evidence of difference in efficacy. The choice of an agent should be a shared decision between the clinician and care recipient as there are a variety of formulations and costs.
While AChEIs were developed for Alzheimer’s disease, evidence also supports the use of AChEIs in other types of dementia, such as vascular dementia, dementia with Lewy bodies, and Parkinson disease dementia, but not for prevention of progression of mild cognitive impairment to dementia.
Side Effects & Risks
Common adverse effects of AChEIs should be considered and counseled (Jackson, Ham, & Wilkinson, 2004):3
Gastrointestinal symptoms such as nausea, diarrhea and anorexia are the most common side effects of AChEIs. These adverse effects are commonly dose dependent.
AChEIs is contraindicated for individuals with known heart block or other cardiac conduction system diseases. Bradycardia is another common side effect of AChEIs, which could increase the risk of fall and syncope, especially among the older adults. Should patients develop significant bradycardia, AChEIs should be discontinued first while addressing other causes of bradycardia.
Evening doses of AChEIs could potentially enhance the activation of visual association cortex during REM sleep, which could cause insomnia and vivid dreams. People who experience sleep disturbances due to AChEIs could consider switching to morning dose.
NMDA Antagonists
Memantine
The mechanism of the action of memantine is distinct from cholinergic agents but not fully understood. It is hypothesized to improve signal to noise ratio, thereby ameliorating NMDA receptor function. There is some research to show it may also be neuroprotective.
A systemic review done in 20085 showed that memantine shows benefits in cognition and on global dementia assessment, but with small effects that are of unclear clinical significance; improvement in quality of life and other domains are suggested but not proven. The benefits are seen mainly in patients with moderate to severe dementia, there is a lack of robust evidence in mild dementia.5
Memantine does not appear to have significant side effects. However, it should be used with caution in patients with a known history of seizures as it lowers seizure threshold and for individuals with chronic kidney disease, renal dosing is recommended.
Aducanumab
In 2021, Aducanumab, a recombinant monoclonal antibody is the first Food and Drug Administration (FDA) approved treatment for Alzheimer’s disease through the accelerated approval pathway. Aducanumab reduces the beta-amyloid plaques, which is the hallmark pathology of Alzheimer’s disease. At present, Aducanumab treatment is limited to persons living with mild cognitive impairment or mild dementia with documented amyloid pathology. APOE4 status check is recommended prior to the initiation of treatment as there is significant risk of amyloid-related imaging abnormalities (ARIA, can present as focal vasogenic oedema of the brain or intracranial hemorrhage) among APOE4 carriers.6 As there is still uncertainty with its clinical benefit, it is currently not available in Singapore.
Antipsychotic Drugs7-10
Many best practice clinical guidelines all over the world have recommended for non-pharmacological interventions to be the first-line of treatment for behaviour changes and symptoms related to dementia. Where possible, non-pharmacological interventions should be attempted before using antipsychotic drugs to address the behaviours.
Antipsychotic drugs can be divided into typical (haloperidol) and atypical (quetiapine, risperidone, olanzapine, etc.). Antipsychotic drugs can be used for treatment of psychotic symptoms including hallucinations, paranoia and delusions when it is critical to the safety, well-being and quality of life of the person living with dementia and their caregiver.
Side Effects & Risks
The side effects include sedation, extrapyramidal disturbances, postural hypotension, QT prolongation, confusion, and falls. Antipsychotic medications are associated with an increased risk of stroke, myocardial infarction and death when used to treat behaviour changes in older adults living with dementia.
Caution needs to be exercised in the use of antipsychotics drugs especially in people living with dementia with Lewy bodies. They may be especially sensitive to antipsychotic medication and may experience idiosyncratic, life threatening adverse reactions.
In conclusion, it is essential to weigh the benefits of the antipsychotic medications in treating the behaviour changes compared to the potential adverse reactions in persons living with dementia. The antipsychotic medications should be maintained only if benefits are apparent, and discontinuation should be attempted at regular intervals.
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1. Trinh, N. H., Hoblyn, J., Mohanty, S., & Yaffe, K. (2003). Efficacy of Cholinesterase Inhibitors in the Treatment of Neuropsychiatric Symptoms and Functional Impairment in Alzheimer Disease: A Meta-analysis. JAMA, 289(2), 210–216.
2. Feldman, H., Gauthier, S., Hecker, J., Vellas, B., Subbiah, P., & Whalen, E. (2001). A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer’s disease. Neurology, 57(4), 613–620. https://doi.org/10.1212/WNL.57.4.613
3. Highlights of prescribing information – Aduhelm. (2021). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761178s000lbl.pdf
4. Jackson, S., Ham, R. J., & Wilkinson, D. (2004). The safety and tolerability of donepezil in patients with Alzheimer’s disease. British Journal of Clinical Pharmacology, 58(1), 1–8. https://doi.org/10.1111/J.1365-2125.2004.01848.X
5. Raina P, Santaguida P, Ismalia A (2008). Effectiviness of cholinesterase and memantine for treating dementia: evidence review for a clinical practice guideline
6. (Highlights of prescribing information – Aduhelm, 2021)
7. Corbett A, Burns A, Ballard C; Don’t use antipsychotics routinely to treat agitation and aggression in people with dementia; BMJ. 2014; 349:g6420 Epub 2014 Nov 3
8. Reus VI, Foctmann Lj, Eyler AE; The American Psychiatric Association Practice Guidelines on the Use of Antipsychotics to treat Agitaiton or Psychosis in Patients With Dementia; Am J Psychiatty. 2016 Nay: 173(5):543-6
9. Antipsychotic drugs for dementia: a balancing act; Lancet Neurol. 2009:8(2):125
10. Sink KM, Hilden KF, Yaffe K. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA. 2005:293(5):596