Medication for Alzheimer's Disease: Some Hope?-Part I

(10/16/06)- About one-half of the patients with Alzheimer's also develop delusions, hallucinations and aggressive behavior. These symptoms worsen with the aging process. Unfortunately a recent study shows that the usage of anti-psychotic drugs does not improve the situation. It is estimated that there are about 5.5 million Americans suffering from AD.

The results of the study, which was done under the leadership of Dr. Lon S. Schneider of the University of Southern California Keck School of Medicine, involved 421 patients at 45 sites from 2001 through 2005. The result of the study was published in the most recent edition of the New England Journal of Medicine.

The study compared the effects of three anti-psychotic drugs with that of a placebo. The drugs were Zyprexa made by Eli Lilly & Co., Rispercal made by J&J and Seroquel made by AstraZeneca.

The patients in each group were treated with low dosages of the drug, which were then increased until the patient either responded positively or could not tolerate the treatment. Clinicians discontinued use of the drugs for between 77% and 85% of the patients involved within nine months, either because the patient could not tolerate the drugs or wasn't getting any benefit.

The researchers concluded that the difference between the placebo and the drugs was not statistically significant and was offset by the higher percentage of patients who dad to discontinue the drugs because of side effects. The study concluded "there is no large clinical benefit of treatment" with the drugs "compared with placebo."

It should be pointed out that the antipsychotic drugs given in the study are used to treat symptomatic behavior related to aggressiveness in AD patients. This is an off label use of these medications. It is used to try to calm AD patients to make them more manageable (especially in nursing homes). Interestingly, placebo worked as well. It suggests that staff in nursing homes may have to try more labor intensive ways to calm residents. There is a need to educate staff in behavioral techniques to achieve goals they thought only could be achieved by medication

(3/19/06)- Eisai Co., of Japan, which co-markets Aricept, the most commonly used Alzheimer's disease drug, with Pfizer Inc., announced that there had been 11 deaths among 648 patients who were taking the drug as part of a Phase III study of patients with vascular dementia. This compared with none of the patients dying among the 326 patients in the group taking a placebo.

The Aricept group of patients had mild to moderate cases of the disease. They were receiving the drug once a day for 24 weeks. The company was hoping that the study would enable the drug to be approved for treating patients with vascular dementia. Vascular dementia is caused by a stroke, or because of diseased blood vessels.

The study was conducted in nine countries and involved only patients with vascular dementia, with no prior diagnosis of Alzheimer's disease. Most of the patients in the study were taking medications to treat previously diagnosed cardiovascular problems.

The FDA is examining the results of the study according to Susan Bro, a spokeswoman for the agency.

The results of this study were similar to the results of a study done several years ago by J&J on Reminyl, a drug similar to Aricept, in which 2,000 patients with AD were followed for two years. Many more patients who were given Reminyl died than those in the placebo group.

According to many health professionals, Aricept, Reminyl, Exelon and Tacrine are similar drugs, and therefore expose AD patients with cardiovascular problems to an increased risk of death from taking these drugs.

(4/20/05)-Johnson & Johnson will change the name of its Alzheimer's disease drug Reminyl to Razadyne starting July 1, in order to avoid confusion with Sanofi-Aventis' similar sounding name drug Amaryl, which is used to treat diabetes. The Ortho-McNeil Neurologics unit of Johnson, which makes the drug also announced that an extended time release version of the drug Razadyne ER would also become available sometime around mid-May of this year.

Ortho-McNeil has been working on the problem with the FDA since last year when it learned of several prescribing and dispensing errors between the two drugs. Ortho-McNeil said that it was aware of two deaths that had taken place because of confusion between the two drugs. Ortho-McNeill alerted health care professionals of the problem back in October 2004. The two drugs were packaged in a similar manner and have a 4-mg dose strength. The confusion between the two drugs also led to several cases of severe hypoglycemia.

The FDA will require "black box" warnings on about the risk of death in elderly dementia patients taking the following medications: Eli Lilly & Co.'s Zyprexia and Symbgax, J&J's Risperdal, AstraZeneca PLC's Seroquel, Novartis AG's Clozaril, Pfizer's Geodon, and Abilify, marketed by Bristol-Myers Squib Co, and Otsuka Pharmaceutical Co.

(6/29/04) As all our readers must know, Alzheimer's Disease is the most common cause of intellectual decline in old age. It is a disorder that can only be definitely diagnosed after death by doing tissue study of the brain. It is estimated that about 4.5 million Americans have Alzheimer's disease, and about a million use one or another of the drugs at an estimated cost of $1.2 billion a year.

There is degeneration of neurons, which result in memory impairment, loss of orientation and changes in personality and behavior. Animal studies indicated that a class of drugs called anticholinergic drugs lead to defects in learning and behavior. The next step would be to prevent the loss of cells and reestablish contacts between cells at their synapses. This is the stage researchers are presently exploring as a therapeutic modality for Alzheimer's Disease. The following are the major medications in use at present that make use of this important fact:

Aricept (Donepezil HCL) has been developed by a company called Eisai America Inc. and is being co-promoted by Pfizer Inc. It is approved for use in mild to moderate Alzheimer's Disease. Side effects noted include nausea, diarrhea and vomiting.

Exelon (ENA-713) Preliminary data from a world wide study of this drug shows promise in providing symptom relief for patients with early to moderate stages of Alzheimer's disease. It is neither metabolized by, nor eliminated by, the liver eliminating certain side effects found in medications. It attempts to block the neurotransmitter that is thought to break down a substance (acetylcholine) needed for cognition and learning.

Tacrine (Cognex) was the first drug approved by FDA for use in Alzheimer's Disease. It retards the progress of the disorder in its early stages. Its major activity is to raise acetylcholine levels in the brain. It has caused some liver problems so it has to be monitored carefully.

At best, these drugs produce slight stopping of the progress of the disorder. There is no cure yet on the horizon for Alzheimer's Disease. Drug companies are looking at over 100 drugs. Researchers in England reported in an article in the journal The Lancet that based on a study of 565 patients, that Aricept did not delay the onset of disability or the need for a nursing home.

The researchers concluded that Aricept has "disappointedly little overall benefit" and is not cost-effective. The 565 patients who participated in the study which was done under the leadership of Richard Gray, a professor of medical statistics at the University of Birmingham, in England were afflicted with mild to moderate Alzheimer's disease. About half of the patients in the study, which was done over a 3-year period of time, were given a placebo, while the other half was given Aricept.

Although the patients taking the drug did have slightly higher scores on mental tests, after three years they did not differ from the placebo group in their rates of being put in a nursing home or becoming disabled. The Alzheimer's Association issued a statement saying that the study should "not dictate individual treatment decisions."

Aricept is the most popular Alzheimer's drug in a class of drugs called cholinesterase inhibitors, approved to treat mild to moderate stages of the disease. Other members of the class include Exelon, Reminyl and Tacrine. The drugs raise the level of a chemical called acetylcholine, which transmits nerve signals in the brain.

Research is now going on using nerve growth factor (NGF) to prevent cholinergic neuron atrophy. It is anticipated that this will improve the functional capacity of those who take it. The Ciba Foundation held a symposium in 1996 on nerve growth factor to explore the use of this drug for neurological and sensory disorders. They reported that when nerve growth factor was used "…the results were that postsynaptic cholinergic system was almost completely spared from degeneration."

Other drugs being explored include MAO-B blockers such as selegiline which works to increase the blood levels of certain neurotransmitters and leads to a cognitive improvement;

Gangliosides have also been shown to slow down the progress of AD by exerting an effect on the synthesis of membrane phospholipids.

Nootropic Drugs exert a regulatory effect on neuronal metabolism, influence synaptic plasticity and learning behavior.

To date, there is no drug that counteracts completely the degenerative process in Alzheimer's.


See: Alzheimer's Disease Part I-Medications for Alzheimer's.
See: Alzheimer’s Disease Part II- Selegiline and AD.
See: Alzheimer's Disease Part III- Use of Gingko Biloba in memory problems of Alzheimer patients
See: Part IV-Alternative Treatments for AD
See: Part V-Possible New Drugs for Alzheimer's Disease
See: Part VI-Early Diagnosis
See: PartVII- Metrifonate
See: Part VIII- Implications of Longer Life Expectancy
See: Part IX-Ethical Care Principles
See: Part X -Estrogen and Alzheimer's Disease
See: Part XI-Pocket Smell Test (PST)
See: Part XII -MAO-B
See: Part XIII -Critical Flicker Fusion Threshold Test
See: Part XIV-Donepezil
See: Part XV-Cerebrolysin
See: Part XVI--MCI
See: Part XVII- Summary
See: Part XVIII--NO Releasing NSAIDs
See: Part XIX--Vitamin E
See: Part XX -Clinical Trials
See: Part XXI- AD and the Brain
See: Part XXII-Lewy Bodies Disease
See: Part XXIV-A Prequel
See: Part XXV- Plus Psychosis
See: Part XXVI- Hypothesis
See: Part XXVII- AD and Diabetes
See: Part XXVIII- Insulin and AD




Harold Rubin, MS, ABD, CRC, Guest Lecturer
updated 12/22/13

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