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This brief summary does not include all information important for patient use and should not be used as a substitute for professional medical advice. Consult the prescribing doctor and read the package insert before using these or any other medications or supplements. Drugs are listed in alphabetical order.
TECHNICAL FACTS
BRAND
NAME | GENERIC
(Int'l) NAME | STAGE OF
ILLNESS | DRUG
TYPE | HOW IT WORKS | LOGO |
ARICEPT®
| donepezil | Mild to moderate & Moderate to severe | Cholinesterase inhibitor | Prevents the breakdown of acetylcholine in the brain. |  |
| EXELON® | rivastigmine | Mild to moderate | Cholinesterase inhibitor | Prevents the breakdown of acetylcholine and butyrylcholine (a brain chemical similar to acetylcholine) in the brain. |  |
| NAMENDA® | memantine | Moderate to severe | N-methyl D-aspartate (NMDA) antagonist | Blocks the toxic effects associated with excess glutamate and regulates glutamate activation. |  |
RAZADYNE®
| galantamine | Mild to moderate | Cholinesterase inhibitor | Prevents the breakdown of acetylcholine and stimulates nicotinic receptors to release more acetylcholine in the brain. |  |
BRAND
NAME | MANUFACTURER’S RECOMMENDED DOSAGE | GENERIC
VERSION? | FORMAT | COMMON SIDE EFFECTS | MORE INFORMATION |
ARICEPT®
| . Initial dose: 5-mg tablet once a day
. May increase dose to 10 mg/day after 4-6 weeks if well tolerated. | No | Tablet | Nausea, vomiting, diarrhea | Visit www.fda.gov/cder. Click on “Drugs@FDA,” search for ARICEPT®, and click on drug-name links to see “Label Information. |
| EXELON® | . Capsule: Initial dose of 3 mg/day (1.5 mg twice a day).
. May increase dose to 6 mg/day (3 mg twice a day), 9 mg (4.5 mg twice a day), and 12 mg/day (6 mg twice a day) at minimum 2-week intervals if well tolerated.
. Patch: Initial dose of 4.6 mg once a day; may increase to 9.5 mg once a day after minimum of 4 weeks if well tolerated.
. Also available as oral solution; same dosage as capsule. | No | Capsule
Patch
Oral Solution | Nausea, vomiting, diarrhea, weight loss, loss of appetite, muscle weakness | Visit www.fda.gov/cder. Click on “Drugs@FDA,” search for EXELON®, and click on drug-name links to see “Label Information.” |
| NAMENDA® | . Initial dose: 5-mg tablet once a day.
. May increase dose to 10 mg/day (5 mg twice a day), 15 mg/day (5 mg and 10 mg as separate doses), and 20 mg/day (10 mg twice a day) at minimum 1-week intervals if well tolerated.
. Also available as oral solution; same dosage as above. | No | Tablet
Oral Solution | Dizziness, headache, constipation, confusion | Visit www.namenda.com. Click on “Prescribing Information” to see the drug label. |
RAZADYNE®
| . Tablet: Initial dose of 8 mg/day (4 mg twice a day).
. May increase dose to 16 mg/day (8 mg twice a day) and 24 mg/day (12 mg twice a day) at minimum 4-week intervals if well tolerated.
. Extended-release capsule: Same dosage as above but taken once a day.
. Also available as oral solution; same dosage as above. | Yes | Tablet
Once-A-Day Extended Release Capsule
Oral Solution | Nausea, vomiting, diarrhea, weight loss, loss of appetite | Visit www.razadyneer.com. Click on “Important Safety Information” to see links to prescribing information. |
2.
Introduction To Medications
Learn about the 4 prescription drugs currently approved by the U.S. Food and Drug Administration (FDA) to treat people who have been diagnosed with Alzheimer’s disease (AD). Treating the symptoms of AD can provide patients with comfort, dignity, and independence for a longer period of time and can encourage and assist their caregivers as well.
It is important to understand that none of these medications stops the disease itself.
Treatment for Mild to Moderate AD
Medications called cholinesterase inhibitors are prescribed for mild to moderate AD. These drugs may help delay or prevent symptoms from becoming worse for a limited time and may help control some behavioral symptoms. The medications include: Razadyne® (galantamine, formerly known as Reminyl® and now available as a generic drug), Exelon® (rivastigmine), and Aricept® (donepezil). Another drug, Cognex® (tacrine), was the first approved cholinesterase inhibitor but is rarely prescribed today due to safety concerns.
Scientists do not yet fully understand how cholinesterase inhibitors work to treat AD, but research indicates that they prevent the breakdown of acetylcholine, a brain chemical believed to be important for memory and thinking. As AD progresses, the brain produces less and less acetylcholine; therefore, cholinesterase inhibitors may eventually lose their effect.
No published study directly compares these drugs. Because they work in a similar way, switching from one of these drugs to another probably will not produce significantly different results. However, an AD patient may respond better to one drug than another.
Treatment for Moderate to Severe AD
A medication known as Namenda® (memantine), an N-methyl D-aspartate (NMDA) antagonist, is prescribed to treat moderate to severe AD. This drug’s main effect is to delay progression of some of the symptoms of moderate to severe AD. It may allow patients to maintain certain daily functions a little longer than they would without the medication. For example, Namenda® may help a patient in the later stages of AD maintain his or her ability to use the bathroom independently for several more months, a benefit for both patients and caregivers.
Namenda® is believed to work by regulating glutamate, an important brain chemical. When produced in excessive amounts, glutamate may lead to brain cell death. Because NMDA antagonists work very differently from cholinesterase inhibitors, the two types of drugs can be prescribed in combination.
The FDA has also approved Aricept® for the treatment of moderate to severe AD.
Dosage and Side Effects
Doctors usually start patients at low drug doses and gradually increase the dosage based on how well a patient tolerates the drug. There is some evidence that certain patients may benefit from higher doses of the cholinesterase inhibitors. However, the higher the dose, the more likely are side effects. The recommended effective dosages of drugs prescribed to treat the symptoms of AD and the drugs’ possible side effects are summarized in the table (see below).
Patients should be monitored when a drug is started. Report any unusual symptoms to the prescribing doctor right away. It is important to follow the doctor’s instructions when taking any medication, including vitamins and herbal supplements. Also, let the doctor know before adding or changing any medications.
Which Alzheimer's medications are best? To help answer this question, the ACP/AAFP Committee issued guidelines on the five available medications for Alzheimer's.
An American College of Physicians (ACP) and American Academy of Family Physicians (AAFP) committee issued a clarifying guideline on drug treatment of dementia. Their advice? When trying to decide which medicine is best for a person, the most important considerations are:
Side effects
Ease of Use
Cost
There's no proof that any one of the five drugs available in the United States to treat dementia in general, and Alzheimer's in particular, is more effective than the others.
The committee reviewed published studies for outcomes such as cognition, global function, behavior/mood, and quality of life/activities of daily living. They found only limited high-quality scientific evidence of the effectiveness of the drugs and therefore developed the following cautious recommendations:
· The decision to use approved drugs for dementia should be based on an individualized patient assessment.
· The choice of drugs should be based on tolerability, adverse effect profile,ease of use, and cost.
· There's an urgent need for more clinical research to improve knowledge about the clinical effectiveness of drugs used to treat dementia.
The committee recommended the following kinds of research:· Evaluate the effectiveness of drug therapy for dementia and assess whether treatments affect key outcomes, such as institutionalization.
· Evaluate the appropriate duration of therapy.
· Head-to-head testing of drugs.
· Test drugs in combination therapy.
The guideline was published in the Annals of Internal Medicine.
Currently, there are five FDA-approved drugs for treatment of dementia. These include four acetylcholinesterase inhibitors - donepezil (Aricept®), galantamine (Razadyne®, Reminyl), rivastigmine (Exelon®), and tacrine - and one neuropeptide-modifying agent - memantine (Namenda®).
While these drugs may improve symptoms or slow disease progression, they don't cure dementia or repair brain damage.
"Doctors, patients and family caregivers desperately want information on how to treat this disease," Dr. Amir Qaseem, senior medical associate in the ACP's Clinical Programs and Quality of Care Department, said in a prepared statement.
"More research is warranted, because the available evidence concerning these pharmaceuticals' effects on quality of life is mixed, and the clinical significance of many of the findings is questionable," Dr. Kenneth G. Schellhase, an AAFP representative on the committee, said in a prepared statement. "In addition, the duration of existing trials was usually less than one year, providing insufficient information to determine the optimal length of treatment, and few trials compare one drug directly with another."
Most existing studies of the five approved dementia drugs focused on statistical significance of changes, but clinically important improvement is what matters to patients, caregivers and doctors, the committee noted. Many studies measuring clinical improvements are currently in progress throughout the world.
People with Alzheimer's and other dementias often take medications called cholinesterase inhibitors.
Medical research has demonstrated they are also a safe alternative to antipsychotics for the behavioral and psychological symptoms of dementia.
This is according to a study that appears in the December 2008 edition of Clinical Interventions in Aging.
Currently, the main cholinesterase inhibitors that are offered for Alzheimer's and other dementias are:
Brand Name | Generic Name |
Aricept | donepezil HCL |
Exelon | rivastigmine |
Razadyne® | galantamine HBr |
Investigators from the Indiana University School of Medicine, the Regenstrief Institute and Wishard Health Services reviewed nine randomized, double-blind, placebo-controlled clinical trials evaluating the effectiveness of three popular cholinesterase inhibitors in managing behavioral and psychological symptoms displayed by patients with Alzheimer's disease.
The researchers report that the trial results indicate cholinesterase inhibitors led to a statistically significant reduction in behavioral and psychological symptoms such as aggression, wandering or paranoia when using the same dosage as administered for improving cognitive impairment.
Nine out of 10 Alzheimer's disease patients display behavioral and psychological symptoms of their disease. The review of the clinical trials revealed that cholinesterase inhibitors are safe, producing no major side effects.
"There is a need for safe alternatives to the anti-psychotic drugs currently used to manage the behavioral and psychological symptoms of Alzheimer's disease. The results of the studies we analyzed are encouraging and suggestive that cholinesterase inhibitors are safe and effective alternatives. However, they are underutilized and typically prescribed for less than three months and for less than 10 percent of patients with Alzheimer's disease. Our findings might provide clinicians with useful data to justify the appropriate use of these medications," said Malaz Boustani, M.D., corresponding author of the Clinical Interventions in Aging paper. Dr. Boustani is assistant professor of medicine at the IU School of Medicine, a Regenstrief Institute research scientist, a research investigator with the IU Center for Aging Research, and chief research officer of the Indianapolis Discovery Network for Dementia.
In Alzheimer's disease there is a decrease in acetylcholine, a chemical in the brain that assists memory, thought and judgment. Cholinesterase inhibitors raise acetylcholine levels. Increased concentrations of acetylcholine in the brain leads to increased communication between nerve cells and may improve or stabilize the symptoms of Alzheimer's disease in the early and moderate stages of progression.
Noll Campbell, PharmD, a clinical pharmacy specialist in geriatric psychiatry with Wishard Health Services and corresponding author of the paper, said that, "This class of medications has already been approved by the Food and Drug Administration to manage symptoms of Alzheimer's-type dementia, although their potential benefits on behavioral symptoms are not frequently identified by many prescribers. Clinical trials of cholinesterase inhibitors have shown benefits in several domains of cognitive function as well as behavioral symptoms associated with dementia, and may improve the management of behavioral problems while reducing the use of more harmful medications that are needed to control behaviors."
Dr. Boustani noted that the vast majority of busy primary care physicians, the doctors who see the majority of patients with Alzheimer's disease, are unaware of the details of the studies analyzed in the Clinical Interventions in Aging paper and he hopes that this new paper, which reviewed the studies, will encourage them to prescribe cholinesterase inhibitors, with its benefits for both cognition and behavior symptoms to their Alzheimer's disease patients.
5. Moderate Your Medications
Almost 190,000 Australians have dementia and as Australia's population ages, dementia becomes a bigger challenge for doctors, their patients and carers.
According to the National Prescribing Service Limited (NPS), there are limited benefits to using cholinesterase inhibitors and memantine in the treatment of patients with dementia drug therapy.
Research indicates that the benefits of cholinesterase inhibitors and memantine are small, some people will not respond and adverse effects are common, says NPS clinical expert, Education and Quality Assurance Program Manager, Ms Judith Mackson.
Because the response rate is low and the effects of cholinesterase inhibitors and memantine are small, if these medicines are to be used, it is imperative that they are monitored in order to objectively assess their effectiveness for the patient.
Antipsychotics have a very limited role in some of the challenging behaviours of dementia and the risk of cerebrovascular events and all-cause mortality increases. Consequentially if there are no clear beneficial effects, a trial withdrawal should be attempted because for many patients symptoms will NOT worsen on withdrawal.
A planned, regular and also opportunistic approach to reviewing medications is recommended not only for people with Alzheimer's disease, but all older people using medicines, Ms. Mackson said.
She says health professionals need to encourage the use of non-pharmacological strategies at all stages of dementia. We know that non-pharmacological strategies can help promote and maintain independence, cognitive function and manage the behavioural and psychological symptoms of dementia.
Carers may see medication as the only option, so they will need support and information to help manage their expectations on the effectiveness of medication, she said. "Appropriate counseling for carers from health professionals on the limited benefits of drug therapy is key to best practice. In addition, carers may need information about the process of withdrawal if there are no clear beneficial effects of the medication."
To learn more about how to make informed decisions when working with patients with dementia, the new NPS education program, Treating the symptoms of dementia may be of interest. To obtain a copy,or to find out about the education program, visit the NPS website www.nps.org.au.
