- Introduction and Drug Classification
- How Aricept (Donepezil) Works – Mechanism of Action
- Effect of Aricept on Alzheimer’s, Lewy Body Dementia, and Vascular Dementia
- Side Effects of Aricept
- Dosage and Tablet Forms of Aricept
- Drug Interactions with Aricept
- Alternatives Treatments
- Donepezil and Memantine Prescribed Together
- Stopping Treatment with Aricept
- Final Thoughts
Donepezil, the generic form of the brand name drug Aricept, is currently the only FDA-approved drug to treat Alzheimer’s disease in all its stages. Aricept may at times be prescribed in combination with Memantine (Namzaric) to treat moderate to severe Alzheimer’s disease.
While Aricept is used specifically to treat Alzheimer’s disease, it can also be used “off-label” to treat mental deficiencies due to other types of dementias such as Lewy Body Dementia. It can be taken in tablet form, capsule, or as a disintegrating tablet. Donepezil does not cure Alzheimer’s disease, but it does work to alleviate and slow the progression of cognitive symptoms such as memory loss.
According to a study published in the New England Journal of Medicine, donepezil demonstrated significant cognitive benefits for Alzheimer’s patients over a span of 12 months. Aricept is part of the drug classification known as cholinesterase inhibitors, which work to prevent the breakdown of certain chemicals in the brain that are crucial to brain cell communication.
Donepezil is known as an acetylcholinesterase inhibitor, or cholinesterase inhibitor, meaning its main mechanism of action is to prevent the breakdown of a neurotransmitter called acetylcholine. Neurotransmitters are chemical messengers that are essential to communication between brain cells (or neurons). More specifically, Aricept inhibits the enzyme (or chemical process accelerator) acetylcholinesterase (ACh), which initiates the breakdown process of acetylcholine in the brain.
It has been found that individuals with Alzheimer’s Disease and certain other dementias have lower levels of acetylcholine. This contributes to their cognitive symptoms, including problems with memory, learning, and confusion. Donepezil stops acetylcholinesterase from breaking down these chemical messengers, and subsequently keeps acetylcholine levels high within the brain, thus improving communication between brain cells, and alleviating memory loss and other symptoms.
Aricept has undergone multiple drug studies in different countries, including Sweden and Japan, that demonstrated its efficacy in treating Alzheimer’s disease. There continue to be studies on donepezil, including its use to treat other types of dementia and research on different delivery systems of the drug.
For example, researchers in Japan have studied donepezil in the form of a transdermal patch, but were declined FDA approval in 2011. Today, there are clinical trials being conducted on the efficacy of donepezil in treating Lewy Body Dementia. Additional research is also being conducted on the effectiveness of donepezil in treating the cognitive symptoms of Vascular Dementia. While many of these studies are ongoing or have produced mixed results, the continued effort to find other uses for Aricept may eventually deem it as an effective treatment for various other types of dementia. Certain dementias, like Frontotemporal Dementia, do not result in depleted acetylcholine levels. Donepezil’s mechanism of action in raising acetylcholine levels thus makes it inappropriate for alleviating cognitive symptoms in these types of dementia. Research into the causes and molecular etiology of different Types of Dementia is necessary to determine appropriate Dementia Treatment.
Physicians often choose Aricept because of the extended duration of a single dose, which allows it to be administered only once daily. There have yet to be concrete studies declaring which Alzheimer’s drug is the most effective with the least amount of side effects. Generally, all the cholinesterase inhibitors used to treat Alzheimer’s and dementia have similar side effects.
While donepezil is usually well-tolerated amongst users, there is, as with all medications, the possibility of side effects. With Aricept, the most common side effects include:
- Weight loss
- Night disturbances
- Gastrointestinal issues such as nausea, vomiting, and diarrhea
Some more serious side effects may include:
- Allergic reactions
- Stomach bleeding
- Slowing of heart rate
As with any medication, side effects should be reported to the patient’s physician as promptly as possible, for the physician may recommend alternative treatments that may not pose negative drug interactions. Gastrointestinal symptoms usually subside after continuous use of donepezil, and it is common to “titrate,” or work up to a higher dose slowly in an effort to minimize the side effects.
Closer Look: Allison’s Mom is Prescribed Aricept
Allison’s Mom, Gail, lives with her and her family after her Alzheimer’s progressed into more moderate stages. Gail has been having more problems with confusion and her memory, and Allison decides to take her mom to the doctor. When, at the appointment, Gail’s doctor suggested that Gail take Aricept to help with her symptoms, Allison was concerned about possible side effects that may outweigh the benefits of the medication for her mother. The doctor thus went over all the possible side effects and explained that the milder ones of gastrointestinal issues such as nausea, vomiting, and diarrhea, usually subsided after a couple of weeks. The doctor reassured Allison, and reminded her that if any severe side effects occurred, to call her immediately. She then prescribed 5mg of Aricept to be taken once daily.
Allison became concerned when her mom experienced some mild nausea and diarrhea throughout the first few days taking the drug, but soon thereafter, her mom began to experience nausea only and not the other possible side effects. After about two weeks of taking Aricept, Gail seemed to be tolerating the drug much better and no longer experienced any side effects. When they went to the doctor the next time, Allison reported her mother’s tolerance of the drug had improved dramatically, and that after taking the drug for a few weeks only, the other symptoms of dementia, most notably memory issues and slight confusion, also seemed to be doing much better. Gail’s doctor felt this dosage was the most appropriate for Gail and wanted her to stay with Aricept for the time being and come back to see her in 3 months unless any serious changes occurred.
Donepezil is usually started at a dose of 5mg once daily, which, while being an effective dose, can easily be increased when necessary to 10mg after about a month of taking the drug. While it is recommended that donepezil be taken before bedtime, if sleeplessness or other sleep issues such as night terrors occur, it can be taken after breakfast instead.
Donepezil is available in immediate release tablet form as well as orally disintegrating tablets at both a 5mg and 10mg dose. The FDA has also approved a sustained-release tablet form at a dose of 23mg that is taken only once daily. The orally disintegrating tablets are useful in patients with swallowing issue because they dissolve on the tongue and require no swallowing.
Furthermore, donepezil should be stored at room temperature and away from moisture, heat, and light. When handling the oral disintegrating tablets, it is important to have dry hands. If a dose of Aricept is missed, it should never be taken twice; instead wait for the next scheduled dosing and continue with the prescribed dosage. Finally, it is highly recommended to never discontinue or alter the dose of donepezil on you own, even when there seems to be improvement in one’s condition. If you feel strongly about wanting to discontinue the medication, consult your doctor and do as the doctor prescribes so as to avoid unnecessary complications.
Here are some of the known interactions:
Drugs that have been known to interact with donepezil include bupropion (brand name Wellbutrin), Acetaminophen, and tramadol. The likelihood of seizures and other complications increase when these drugs are taking with donepezil.
Other drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin can increase the risk of stomach or intestinal bleeding when taken with donepezil.
It is important to consult with the patient’s physician before starting or stopping current medication regimens, and it is equally important to have an up-to-date medication list at every doctor appointment in an effort to avoid miscommunication and the possibility of other dangerous drug interactions.
Some individuals with dementia may not respond to Aricept, and some others may not be able to tolerate the side effects. Some alternatives to donepezil include:
The other cholinesterase inhibitors approved by the FDA to treat Alzheimer’s disease. These include Rivastigmine (brand name Exelon), and Galantamine (brand name Razadyne). Switching may offer some benefit or relief, but because these drugs are of the same class, they have similar mechanisms of action and side effects.
Another option is Memantine, brand name Namenda. Memantine is at times prescribed for those with moderate to severe Alzheimer’s who cannot tolerate the side effects of the cholinesterase inhibitors. Memantine is a NMDA Antagonist whose specific action is to regulate the levels of glutamate in the brain. When glutamate levels become too high, they can cause damage that leads to the death of brain cells. It is important to never suddenly stop, change, or adjust medication on your own and make sure to always consult with a physician about the need to stop any medication or make adjustments in dosages.
In people with moderate to severe Alzheimer’s or other types of dementia, donepezil and memantine have been known to be prescribed in combination, or together. The brand name for this prescription combination is Namzaric. Both these drugs act upon different chemicals in the brain, and their combination is believed to have an added benefit for some individuals.
While donepezil increases the levels of acetylcholine in the brain, therefore increasing communication between brain cells, memantine lowers the level of glutamate, which at high levels can damage and kill brain cells. Therefore, these drugs work to alleviate cognitive symptoms such as problems with memory and confusion or disorientation, but they simply do so in different ways.
Another additional benefit seen with this combination therapy of donepezil and memantine is an improvement in behavioral symptoms such as agitation. Lastly, patients experiencing uncomfortable side effects like diarrhea due to donepezil can sometimes experience some relief due to memantine’s side effect of constipation.
There have also been studies that show that individuals with moderate to severe dementia can benefit greatly from the combination therapy of these two drugs, while one recent study showed that donepezil alone was more effective than the combination therapy of donepezil and memantine. These types of mixed results demonstrate another difficulty of Alzheimer’s drugs in that some individuals are more responsive to the medications than others; there is no one size fits all drug therapy with Alzheimer’s and dementia. In addition, the fact to remember with these drugs is that they do not offer a cure, but rather the possibility of temporary relief from cognitive symptoms. Nevertheless, while patients in some of these studies did not benefit from combination therapy, there is research to show that others experienced relief.
Closer Look: Bob’s Benefit from Combination Therapy
Alfred became the primary caregiver for his uncle Bob after he was diagnosed with Alzheimer’s disease about 5 years earlier. Alfred’s father and Bob were twins, and Alfred grew up in very close proximity to his uncle who always treated him like a son. Bob in time progressed into the more moderate stages of the disease and has been on donepezil for about 12 months.
While Bob seems to be doing well, he has recently experienced increased levels of agitation. Alfred decided to bring up the agitation and the fact that he felt the medication was no longer working to Bob’s physician. The doctor felt it would be best for Bob to stay on the donepezil and explained that even though he may not seem to be improving, Bob was staying at a higher functioning level cognitively and avoiding a natural decline, which the doctor believed was because of the medication. The doctor further assessed that if there were any other factors, such as sudden life changes or new medications, that those may be contributing to Bob’s agitation. After another few weeks, and having ruled out these other possible contributing factors, Bob’s doctor decided to prescribe Namzaric, the combination drug of donepezil and memantine, to see specifically if it would help with Bob’s agitation. He told Alfred to start this drug, which contained the dose of donepezil that Bob was currently taking, and to discontinue the other donepezil he had left at home.
About a month later, Alfred took his uncle in for a follow-up visit to the doctor. Alfred reported that Bob’s agitation was doing much better, and that his cognition remained the same. Bob’s doctor was pleased to hear this, and he informed them both that for now this may currently be the best medication treatment for Bob. He told Alfred to schedule a follow-up visit again in another month, but that he needed to come sooner if he observed any other changes or decline in confusion or other cognitive faculties.
It is important to never discontinue any drug treatment without consulting your physician. Most of the time, the decision to discontinue Aricept is due to intolerable side effects or because of a misconception that the drug has achieved its objectives. Your loved one’s physician is the best source of information and instruction about discontinuing medications. Some individuals with dementia and their loved ones also on occasion wish to discontinue donepezil because they feel there is no noticeable difference with regards to symptoms and the overall status of the person’s condition. With Aricept, emerging studies have shown that if tolerated well, it may be best to remain on the medication until the latter stages of Alzheimer’s or other diseases it was being prescribed for. Studies have demonstrated that individuals who discontinued donepezil prematurely ended up declining more rapidly than those who remained on the medication. Even in cases where there was no noticeable improvement in the person’s condition, the decline was subsequently far less rapid, and these people were able to remain at a functional level cognitively for a longer period of time.
Donepezil remains one of the longest used drugs for the treatment of Alzheimer’s disease and other types of dementia. While the drug may offer temporary relief from the harsher aspects of dementia symptoms, it is not a permanent solution to the disease. Alzheimer’s disease and other dementias are progressive and have no known cures, and although Aricept may offer relief for a temporary period of time, it will eventually become increasingly less effective as the disease progresses into the later stages. It is important to remember that not all patients respond to treatment with donepezil in the exact same way, and that this period of relief will therefore affect patients differently. Even so, knowing about the medication options and how they work not only empowers caregivers, but also helps by creating a personalized treatment plan with a specific goal for their loved ones with dementia.