Namenda Treatment for Moderate to Severe Alzheimer’s

About Namenda

A medication known as Namenda (memantine), an N-methyl D-aspartate (NMDA) antagonist, is prescribed to treat moderate to severe Alzheimer’s disease. This drug’s main effect is to delay progression of some of the symptoms of moderate to severe Alzheimer’s. 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 the disease 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.

Namenda was approved in October 2003 by the Food and Drug Administration for the treatment of moderate to severe Alzheimer's disease. The approval was based partly on a rigorous 28-week study of 252 people who were randomly chosen to receive the drug or a placebo. The results, published in the prestigious New England Journal of Medicine in the spring of 2003, showed that the drug could slow the downward spiral of the disease.

Therapeutic Effect

Namenda is proven to help treat the symptoms of moderate to severe Alzheimer's disease. That is important because the longer symptoms are treated, the more quality time you may have to spend with the person with Alzheimer's disease who you are caring for.

In a 28-week study, mentioned earlier, published in the New England Journal of Medicine patients suffering from moderate to severe Alzheimer's disease received either 20 mg of Namenda per day or a placebo (sugar pill). The study found that compared to patients taking placebo:

• Patients taking Namenda experienced a slower rate of decline in thinking over time.
• Namenda treated patients had significantly greater ability to perform daily activities, including doing household tasks such as taking out the garbage or clearing the table after dinner, as well as conversing.

Namenda in combination with donepezil may do more to treat the symptoms of moderate to severe Alzheimer's disease then donepezil alone.

Since so far there is no cure for Alzheimer's disease, the goal of treatment with Namenda, as with all Alzheimer's disease medications, is to treat the symptoms of Alzheimer's disease. Once treatment is started, you may wonder how long it will take for Namenda to have an effect. Some patients have seen an improvement within twelve weeks of starting therapy, although individual results may vary.

Please keep in mind that either no change in Alzheimer's disease symptoms or a slower rate of progression of symptoms are positive results compared to the more rapid decline a person with Alzheimer's disease might experience without treatment. It is important to understand that every day symptom progression is delayed may allow the person with Alzheimer's disease to spend more quality time with his or her loved ones.

How it works?

Namenda works in a unique way and is different from other prescription medications approved to treat Alzheimer's disease. As the only NMDA receptor antagonist, Namenda targets a brain chemical known as glutamate. Nerve cells rely on a variety of chemical messengers to transmit messages from one cell to the next. One of those chemical messengers is glutamate.

Glutamate is a chemical in the brain that has been associated with learning and memory. Abnormal glutamatergic activity in the brain may lead to Alzheimer's disease symptoms. Namenda may help block abnormal glutamatergic activity to improve symptoms.

Other Alzheimer's disease medications, known as AChEIs (acetylcholinesterase inhibitors), such as Aricept (donepezil), work by targeting a different brain chemical called acetylcholine. When there is too little acetylcholine in the brain of a person with Alzheimer's disease, memory and learning can be affected. AChEIs work by addressing that problem.

Taking Namenda alone or in combination with donepezil may help improve quality of life for people with Alzheimer's disease and their caregivers. There is no evidence that Namenda prevents or slows neurodegeneration in patients with Alzheimer's disease.

Taking Namenda

Getting Started

Therapy begins at a low dose (5 mg per day) and is gradually increased until the recommended target dose (10 mg, twice daily) is reached. A common dosing schedule for beginning Namenda therapy is provided below:

Recommended Namenda dosing schedule

1. Week 1: Start on Day 1

Take one 5 mg tablet in the morning, each day.

2. Week 2: Start on Day 8

Take one 5 mg tablet in the morning and one 5 mg tablet at night, each day.

3. Week 3: Start on Day 15

Take one 10 mg tablet in the morning and one 5 mg tablet at night, each day.

4. Week 4: Start on Day 22

Take one 10 mg tablet in the morning and one 10 mg tablet at night, each day.

5. Once the recommended target dose (10 mg, twice daily) has been reached, people taking Namenda can continue with that daily regimen unless instructed otherwise by their doctors (For patients with severe renal impairment, 5 mg twice daily is the recommended dose).

Side Effects

Although generally well-tolerated, the most common side effects are dizziness, headache, constipation, and confusion. Unlike cholinesterase inhibitors such as Aricept, Exelon, and Razadyne, those taking Namenda have a low risk of gastrointestinal side effects.

Potential Interactions

Namenda has a low potential for drug interactions. However, other NMDA antagonist medications, which include some cold and flu medications (like dextromethorphan), should be used with caution while taking Namenda. Sometimes, doctors prescribe Namenda along with a cholinesterase inhibitor to treat moderate Alzheimer's disease, as some studies have shown additional benefit from combining these medications.

Sources and Additional Information:

http://www.nia.nih.gov/Alzheimers/Publications/medicationsfs.htm

http://www.namenda.com/

http://alzheimers.about.com/od/treatmentofalzheimers/p/namenda.htm

http://www.healthyplace.com/alzheimers/medications/memantine-namenda-for-treating-alzheimers/menu-id-72/

http://www.medicalnewstoday.com/articles/35952.php

Cholinesterase inhibitors for Alzheimers disease patients

Overview

Medications called cholinesterase inhibitors (or Acetylcholinesterase inhibitors (ACIs)), are regularly prescribed to the patients with mild to moderate Alzheimer’s Disease. These drugs may help delay or prevent symptoms from becoming worse for a limited time and may help control some behavioral symptoms as well. 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.

How It Works

Cholinesterase inhibitors increase the level of a brain chemical called acetylcholine. People with Alzheimer's disease and related conditions have decreased brain levels of this neurotransmitter. Increasing the amount of acetylcholine appears to slow mental decline in people with Alzheimer's disease.

These medicines help the brain cells work better but do not stop or reverse the destruction of brain cells and loss of acetylcholine that occur in Alzheimer's disease. They do not prevent the disease from getting worse but may slow the progression of symptoms.

How Well It Works

Cholinesterase inhibitors may produce small improvements in memory and general ability to function. For example, the person may be able to remember friends' names better and be able to dress himself or herself with less difficulty.

• Studies have shown that people with mild to moderately severe Alzheimer's who took donepezil scored somewhat higher in their doctors' evaluations of their mental and functional status than those who did not take the drug.
• Studies show that rivastigmine has beneficial effects similar to donepezil. Rivastigmine has more side effects, including nausea and possible weight loss. Because of the side effects, more people stop treatment with rivastigmine.
• Galantamine is available in the United States. It may improve memory and thinking abilities.
• Improvement with cholinesterase inhibitors usually is minimal. The person's mental status does not stabilize, but the rate of decline may be somewhat slower than it would be without the medicine.
• Improvement in symptoms may be more likely at higher doses, but higher doses also may cause more side effects.
• Doctors don't know for sure that cholinesterase inhibitors help with behavior problems in people who have Alzheimer's disease. Some studies show that these medicines do help, which can mean less burden on caregivers. But other studies show that these medicines do not help.
• Cholinesterase inhibitors may have some use in other dementias, such as dementia with Lewy bodies and multi-infarct dementia.

Cholinesterase inhibitors do not help everyone who has Alzheimer's disease. It is believed that as the disease progresses, the medicine eventually may stop working.

The various cholinesterase inhibitors have similar effects on memory and cognitive function, so the choice between medicines may be based on side effects, dosing schedules and ease of use, individual response to a particular medicine, or other factors.

Dosage

Donepezil (Aricept) - 10 mg/day, as a single dose

Galantamine (Razadyne) - 24 mg/day, in 2 divided doses

Rivastigmine (Exelon) - 12 mg/day, in 2 divided doses

Tacrine (Cognex) - 160 mg/day, in 4 divided doses (this agent has largely been replaced with other available acetylcholinesterase inhibitors with more favorable dosage regimens and adverse event profiles).

Duration of Therapy

Acetylcholinesterase inhibitors do not alter the long-term progress of Alzheimer’s disease, but have been shown to delay the time to institutionalization, which may be cost-effective. Acetylcholinesterase inhibitors may be prescribed to stabilize dementia in Alzheimer’s patients, as determined by periodic assessment of functional and cognitive ability. Acetylcholinesterase inhibitors should be discontinued when dementia becomes unresponsive to therapy and progressively severe, as the efficacy of these agents diminishes due to loss of intact cholinergic neurons.

Side Effects
In general, most people seem to tolerate cholinesterase inhibitors very well. The most common side effects are:

• Nausea.
• Diarrhea.
• Vomiting.
• Indigestion.
• Abdominal pain.
• Loss of appetite and weight loss.

Less common side effects include insomnia, fatigue, and muscle cramps. Side effects tend to be mild and usually go away within a few weeks after treatment with the medicine is started.

What to Think About

Cholinesterase inhibitors do not work for everyone who has Alzheimer's disease, but they are helpful for some people. They may be a reasonable option for those who understand the risks and costs and feel the possible benefits are worth it.

Most studies of cholinesterase inhibitors for people with Alzheimer's disease found that the benefits of taking these medicines are small.

Side effects seem to be milder and occur less often with donepezil or galantamine than with rivastigmine.

Experts agree that reducing problems with memory loss may help people with Alzheimer's disease live better. In some cases, reducing these problems may help people live more independently for a longer period of time.

Rivastigmine (Exelon) can now be given through a skin patch. Skin patches release medicine into the blood at a steady level and may reduce side effects. And it’s easier for caregivers to make sure a person is taking the medicine properly when the person uses a skin patch.

Selective Researches

Dr Raschetti and colleagues at Italy's National Centre for Epidemiology, Surveillance and Health Promotion in Rome conducted a systematic review of the data from clinical trials that had addressed the use of cholinesterase inhibitors with Mild Cognitive Impairment (MCI) patients. In none of the six trials that they examined did the use of the drugs significantly reduce the rate of progression from MCI to dementia.

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. 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.

Sources and Additional Information:

http://www.nia.nih.gov/Alzheimers/Publications/medicationsfs.htm

http://health.msn.com/health-topics/neurological-cognitive-health/articlepage.aspx?cp-documentid=100063018

http://www.news-medical.net/news/2007/11/27/32950.aspx

http://www.physorg.com/news148048746.html

http://www.hhsc.state.tx.us/hcf/vdp/Criteria/acetylcholinesterase.pdf