Edited and reviewed by Ali Haider Mohammed, Lecturer at School of Pharmacy, Monash University Malaysia

“Dementia is not a specific disease but is a general term for the impaired ability to remember, think, or make decisions that interfere with everyday activities. Alzheimer’s disease is the most common type of dementia.” – CDC ⁵

When I returned to my hometown, my grandmother could no longer remember who I was. That is how Alzheimer’s chewed me away from her memories permanently. However, little did we know that there is a reversible version of dementia, which is delirium. This may stem from possible side effects of medications, increased pressure in the brain, vitamin deficiency and thyroid hormone imbalance.⁵ Here in this article, we will focus on the common medicines with anticholinergic properties that silently wipe away the memories of our loved ones. As you go through this article, remember the pathophysiology of delirium to help you understand how the medications mentioned below result in worsening symptoms due to a deficit of acetylcholine.¹ It is helpful to note that an excess of glutamate will also cause an influx of calcium ions into the NMDA receptor resulting in the death of cells.¹

Antihistamines

Cetirizine, levocetirizine, loratadine and desloratadine may worsen the condition of patients with dementia.⁶ At the same time, the more sedative 1st generation antihistamines such as chlorpheniramine, promethazine, diphenhydramine and doxylamine should be avoided if patients are found to have symptoms of dementia.¹

Antidepressants

Fluvoxamine and venlafaxine can worsen dementia symptoms.⁶ Amitriptyline, nortriptyline and paroxetine should be avoided as they have the highest affinity to the muscarinic receptors.¹ Serotonin Reuptake Inhibitors (SSRIs) such as sertraline and citalopram are preferred due to their lower tendency to interact with other medications commonly used for treating Alzheimer’s Disease.^{2, 6} However, mirtazapine and sertraline appear less effective than the other antidepressants.⁴

Antipsychotics

Non-drug treatment options should be applied before considering drug treatment for psychosis.⁸ Aripiprazole, risperidone and haloperidol may precipitate delirium, while clozapine, chlorpromazine, quetiapine and olanzapine have a high tendency to worsen delirium.⁶ The antipsychotic of choice in patients with dementia is risperidone, as it has the most evidence available.³ For the treatment of psychosis in Alzheimer’s Disease, mixed Alzheimer’s Disease, and vascular dementia, the Australian Therapeutic Guideline prefers risperidone and olanzapine, followed by aripiprazole as the second choice if the former two options are not available or not suitable.⁷

In dementia with Lewy bodies, antipsychotics are not recommended as there is insufficient evidence to support their uses.⁷ If an antipsychotic is needed, low-dose quetiapine is the best choice as it causes less severe sensitivity reactions and is least likely to worsen motor symptoms.⁸ The other option is clozapine as it has less interaction with medicines for dementia, which is true for quetiapine as well.³ However, they might cause falls due to the tendency to cause drowsiness and dizziness. Generally speaking, atypical antipsychotics are preferred over the typical antipsychotics in this group of patients.⁸

Cardiovascular Medications

Atenolol, metoprolol, nifedipine, captopril, digoxin and isosorbide potentially result in delirium.⁶ Atropine should be avoided if possible.⁶ Diuretics, especially furosemide, precipitate delirium by inducing dehydration and electrolyte imbalance.¹ Digoxin disrupts neuronal activity as it inhibits the sodium-potassium pump.¹

Antimuscarinics (Urinary)

Darifenacin, flavoxate, propiverine, solifenacin, trospium, tolterodine, oxybutynin and orphenadrine are not suitable for patients who are prone to delirium, as they will block the acetylcholine, which is vital in the neurotransmission of signals.⁶

Opioids 

Codeine, fentanyl and morphine may worsen delirium due to their tendency to cause constipation and confusion.⁶ It is helpful to note that under-treatment of pain will result in confusion as well.⁸

Benzodiazepines 

Delirium may be worsened by benzodiazepines, especially alprazolam and diazepam.⁶ Adverse effects such as cognitive decline, sedation, and urinary incontinence put the patients at risk of deteriorating confusion, increasing the risk of falls and hip fractures, not to mention the possibility of dependence.^7,8 In cases when benzodiazepines must be prescribed, one with a shorter half-life, such as lorazepam, is preferred.⁸

Chronic Obstructive Pulmonary Disease (COPD) Drugs 

Theophylline and certain anticholinergics such as ipratropium, tiotropium, glycopyrronium, umeclidinium and aclidinium are known to precipitate delirium, especially in elderlies.^1,4

Other Medications

It is best to avoid amantadine, carbamazepine and oxcarbazepine to avoid worsening of delirium.⁶ As prescribers and dispensers, we must be aware that warfarin, cimetidine, hyoscine and certain steroids such as hydrocortisone and prednisone may escalate the state of delirium.⁶

When all the modifiable factors were ruled out, one should consider starting an anticholinergic, such as donepezil, rivastigmine and galantamine; and NMDA receptor antagonist, such as memantine, is beneficial to the patient.⁸ I will also include a table of the anticholinergic burden score (ACB) here as a reference for the choice of drug therapy in delirious patients:⁶

Here is another table from the Australian Medicine Handbook (AMH):⁴

Reference:
1. Alagiakrishnan K and Wiens CA. An approach to drug induced delirium in the elderly. Postgrad Med J. 2004; 80(945):388-393. Available from: https://pmj.bmj.com/content/80/945/388
2. Alzheimer’s Association. Depression [Internet]. Chicago: Alzheimer’s Association; [reviewed 2019 Apr 5; cited 2022 Oct 20]. Available from: https://www.alz.org/help-support/caregiving/stages-behaviors/depression#:~:text=Antidepressants%20called%20Selective%20Serotonin%20Reuptake,causing%20interactions%20with%20other%20medications 20].
3. Alzheimer’s Society. Antipsychotics and Other Drug Approaches in Dementia Care [Internet]. London: Alzheimer’s Society; [reviewed 2021 Aug 13; cited 2022 Oct 20]. Available from: https://www.alzheimers.org.uk/about-dementia/treatments/drugs/antipsychotic-drugs#:~:text=The%20off%2Dlabel%20antipsychotics%20most,other%20symptoms%20of%20these%20conditions
4. Australian medicines handbook online [Internet]. Adelaide (AU): Australian Medicines Handbook Pty Ltd; 2000. Drugs with Anticholinergic Effects; [updated 2022 Jul; cited 2022 Oct 17]. Available from: https://amhonline-amh-net-au.ezproxy.library.uq.edu.au/
5. Centers for Disease Control and Prevention (CDC) [Internet]. What is Dementia? Atlanta (GA): Centers for Disease Control and Prevention (US); [reviewed 2019 Apr 5; cited 2022 Oct]. Available from: https://www.cdc.gov/aging/dementia/index.html#:~:text=Dementia%20is%20not%20a%20specific,a%20part%20of%20normal%20aging
6. Clinical Practice Guideline: Management of Dementia, 3rd Edition. Putrajaya: Ministry of Health, Malaysia; 2021.
7. eTG complete [Internet]. Melbourne (AU): Therapeutic Guidelines Ltd; 2017. Dementia [updated 2021 Mar; cited 2022 Oct 17]. Available from: https://tgldcdp-tg-org-au.ap1.proxy.openathens.net/viewTopic?etgAccess=true&guidelinePage=Psychotropic&topicfile=dementia&guidelinename=Psychotropic&sectionId=toc_d1e1429#toc_d1e1429
8. Press D. Management of neuropsychiatric symptoms of dementia [Internet]. Available from: https://www.uptodate.com/contents/treatment-of-alzheimer-disease?search=dementia&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2

The information provided should not be used for diagnosing or treating a health problem or disease, and those seeking personal medical advice should consult with a licensed physician. Always seek the advice of your doctor or other qualified health provider regarding a medical condition.

Published on December 28, 2022