Drugs for Dementia Treatment Options and Risks

The Bottom Line

A decline in cognitive function can occur with aging and, if it interferes with daily activities, it might be diagnosed as dementia. Several drugs can produce small improvements in dementia symptoms. Adverse effects of these drugs occur frequently, and evaluation in a healthcare facility is often necessary if a person takes too much.

The Full Story

Cognitive function refers to a person's ability to learn, remember, and reason. Many people experience some loss of cognitive function with aging. Dementia is the impairment of cognitive functioning severe enough to disrupt daily life and activities. The examples below illustrate some of the ways in which dementia differs from typical age-related changes:

Alzheimer's or other dementias
Typical age-related changes
Memory loss that disrupts daily life – forgetting recently learned information or important dates, asking for the same information over and over, needing frequent reminders for things that one used to handle routinely.
Sometimes forgetting names or appointments,
but remembering them later.
Difficulty in planning or solving problems – can have trouble following a familiar recipe, keeping track of bills, counting change, concentrating.
Making occasional errors when balancing a checkbook.
Difficulty completing familiar tasks – trouble driving to a familiar location, managing a budget, remembering rules of a favorite game.
Occasionally needing help to use a microwave oven or functions on a cell phone.
Confusion about time or place – losing track of dates, seasons, passage of time, one's location.
Being confused about the day of the week, but figuring it out later.
Trouble with words – difficulty participating in conversation or finding the right words.
Sometimes having trouble finding the right word.
Poor judgment – spending money unwisely, less attention to grooming and staying clean.
Making a bad decision once in a while.
Withdrawal from normal activities – avoiding social events, hobbies, sports, and other activities due to loss of cognitive functions such as conversational ability and memory of how to do things.
Sometimes feeling the need to escape work, family, and social obligations.

The most common cause of dementia is Alzheimer's disease (AD), but dementia can occur also with Parkinson's disease (PD) and some other neurologic disorders. Currently, one in 10 Americans aged 65 years and older has Alzheimer's dementia, and people aged 75 years and older are at greatest risk. The symptoms of AD are associated with damage to neurons (nerve cells) in the brain that make acetylcholine (ACh), a neurotransmitter. These neurons are plentiful in areas of the brain associated with thinking and memory. When they are damaged, ACh levels fall and the cognitive function of those areas is reduced.

What Are the Treatment Options?

Medications to help curb the symptoms of AD first appeared 25 years ago. Tacrine (Cognex) was the first drug approved for dementia treatment. Tacrine acted by inhibiting the enzyme acetylcholinesterase (AChE), which would normally break down ACh. This preserves ACh levels in the brain and results in better cognitive function. Tacrine is now off the market, but three newer AChE inhibitors are available: donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne). A fourth drug, memantine (Namenda), acts in a different way to reduce dementia symptoms. Memantine blocks a receptor in the brain (NMDA receptor) to interfere with the neurotransmitter glutamate. It is thought that over-excitation by glutamate might contribute to the death of neurons in AD.

All four of these medications for dementia are available as generics. The three AChE inhibitors are about equally effective in treating mild to moderate Alzheimer's disease. They produce small but measurable improvements in dementia symptoms, but do not stop or reverse the disease. They have also been used to treat cognitive impairment in Parkinson's disease (PD), but can occasionally cause worsening of PD symptoms such as tremor. Rivastigmine is the only AChE inhibitor approved to treat PD dementia.

Memantine has been studied in patients with moderate to severe dementia and it has modest beneficial effects. There are no scientific studies that compare the effectiveness of memantine with the AChE inhibitors, so we don't know if one category of drugs works better than the other. Increasingly, some patients are taking an AChE inhibitor along with memantine. Research so far has not shown a clear benefit for taking a combination of AD drugs. The following table compares important features of the four individual AD medications, as well as a medication containing both memantine and donepezil.

Current Medications for Dementia

Generic name

Forms available

Category

Notes

Tacrine

N/A

AChE inhibitor

Off the market

Donepezil

Oral tablets

AChE inhibitor

Most commonly prescribed AD drug; lowest risk for side effects of the AChE inhibitors

Rivastigmine

Oral capsules, transdermal patch

AChE inhibitor

Patch causes fewer GI side effects than the oral capsules

Galantamine

Oral tablets, liquid, extended-release capsules

AChE inhibitor

Derived from daffodil bulbs

Memantine

Oral tablets, liquid, extended-release capsules

NMDA receptor blocker

Fewer adverse effects than with AChE inhibitors

Memantine/donepezil
(Namzaric)

Extended-release capsules

NMDA receptor blocker/AChE inhibitor

No evidence for consistent benefit of combination capsule, and not available as a generic


Does Treatment Have a Downside?

AChE inhibitors can cause gastrointestinal (GI) effects such as nausea, vomiting, and diarrhea – especially when the medication is first started or the dosage is increased. Taking with food can lessen the GI effects. The patch form of rivastigmine causes fewer GI side effects than the corresponding oral capsules. Slowed heart rate, faintness, falls, and hip fractures might occur less commonly when AChE inhibitors are taken. Memantine tends to have fewer side effects than the AChE inhibitors. Side effects reported for memantine include dizziness, confusion, agitation, insomnia, and hallucinations. When memantine is taken together with an AChE inhibitor drug, GI side effects of the AChE inhibitor seem to occur less frequently.

The risks for adverse effects are increased if someone takes too much of an anti-dementia drug. The two patient groups most often affected are toddlers who take the medication unintentionally and people over 70 years of age who unintentionally take too much of their own medication. Children often get the medications from an adult's purse or open medication container. Dementia patients might take extra medicine if they don't recall already having taken their dose. The most common symptoms resulting from unintentional overdoses are vomiting, diarrhea, and drowsiness. About half of the overdoses reported to Poison Control are referred to an emergency room because of the risk for more serious symptoms such as lowered heart rate and mental changes that can last for several days.

When it comes to avoiding toxicity from anti-dementia medicines, the best approach is prevention. Drugs should be stored in child-resistant containers, and small children must be closely supervised when visiting grandparents and others who might have inadequately "child-proofed" their homes. Daily pill organizers are handy, but they are not child-resistant. AD patients sometimes need help keeping track of medicines, so make sure that someone is available to assist them if necessary.

If you have questions about an adverse reaction or possible overdose of one of the drugs for dementia, immediately check the webPOISONCONTROL® online tool or call Poison Control at 1-800-222-1222 for help 24 hours a day, every day.

Leslie A. McCament-Mann, PhD, RPh
Clinical Toxicologist


For More Information

2019 Alzheimer's Association facts and figures. Chicago: Alzheimer's Association; 2019 [cited 10 May 2019].

Alzheimer's disease & related dementias. Bethesda (MD): National Institute on Aging; [updated 2019 Apr 30; cited 10 May 2019].

Medication safety. Chicago: Alzheimer's Association; 2019 [cited 12 May 2019].

Medications for memory. Chicago: Alzheimer's Association; 2019 [cited 10 May 2019].


References

Buckley JS, Salpeter SR. A risk-benefit assessment of dementia medications: systematic review of the evidence. Drugs Aging 2015 Jun;32:453-67.

Hansen RA, Gartlehner G, Webb AP, Morgan LC, Moore CG, Jonas DE. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer's disease: a systematic review and meta-analysis. Clin Interv Aging 2008;3(2):211-25.

McCain KR, Sawyer TS, Spiller HA. Evaluation of centrally acting cholinesterase inhibitor exposures in adults. Ann Pharmacother 2007 Oct;41(10):1632-7

Shi X, Lin X, Hu R, Sun N, Hao J, Gao C. Toxicological differences between NMDA receptor antagonists and cholinesterase inhibitors. Am J Alzheimers Dis Other Demen 2016 Aug;31(5):405-12.

Thornton S, Pcheinkova KL, Cantrell FL. Characteristics of pediatric exposures to antidementia drugs reported to a poison control system. J Pediatr 2016 May;172:147-50.

Poisoned?

Call 1-800-222-1222 or

HELP ME online

Prevention Tips

  • Keep prescription drugs, over-the-counter medications, and dietary supplements in child-resistant containers and away from children and pets.
  • Grandparents and older relatives often have medications that are especially hazardous if taken incorrectly or by a child. Extra precautions are needed to reduce dosing errors and unintentional poisonings. Talk to your pharmacist and check the Alzheimer's Association website to find out about ways to ensure safe storage and use of drugs used for dementia.
  • Ask your pharmacist about possible drug interactions and adverse effects of your medications. If you have questions about a possible problem, contact your physician or Poison Control for treatment advice.

This Really Happened

Case 1. An 84-year-old AD patient developed vomiting and diarrhea after receiving his first two doses of newly prescribed rivastigmine. He took a 4.5 mg rivastigmine capsule in the evening and another 4.5 mg capsule the next morning. The initial dosage for rivastigmine oral capsules is usually 1.5 mg twice a day, so he received three times the normal starting dosage. The vomiting and diarrhea resolved gradually over the next day, and his caregiver was advised to contact the patient's physician about the adverse effects and high dose that was prescribed.

Case 2. An 89-year-old AD patient was seen in an emergency room because she was confused, agitated and delirious, and had slurred speech. Tests for stroke were negative. Four rivastigmine patches were discovered on her upper arm. She had been administering her own medication and did not know she needed to remove one patch before applying another. She was admitted to the hospital for observation and, once the patches were removed, her symptoms resolved within 24 hours. She did not suffer any of the GI side effects of rivastigmine, which is typical since the patch is known to cause fewer GI effects than the oral capsule formulation.

Case 3. A 68-year-old woman called Poison Control after unintentionally taking an extra tablet of her memantine 10 mg when she got up during the night. She had taken her normal evening dose of memantine several hours earlier. She complained of dizziness. Minimal toxicity was expected from taking one extra dose, and the dizziness resolved by morning.