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Monday, May 23, 2011

Public Citizen Wants FDA to Ban Aricept 23

I found this article on the Dementia Weekly website. I cannot say that I agree since I have seen some dramatic results from taking Aricept 23. Yes, there are side effects, but most of the the side-effects go away after a few weeks. Why should some interfering pseudo do-gooders want to make it more difficult for those of us impacted by dementia to make our own decisions. Nobody is forcing anyone to take Aricept. We need to have more, not fewer, choices.  If it works for even a few of us it should be available.

They are not saying that Aricept does not work. They are just saying that there isn't a benefit to taking 23mg over 10mg. I must disagree. In my case I think I did see a difference. Of course Aricept is not approved for FTD anyway, so I guess that doesn't count.

WASHINGTON, D.C. – A drug used to treat moderate or severe cases of Alzheimer’s disease should be removed from the market immediately because of its risk of serious adverse effects and its lack of effectiveness, Public Citizen and an eminent geriatrician from Johns Hopkins said in a petition filed today with the Food and Drug Administration (FDA).

Donepezil, also known as Aricept, has been approved by the FDA in a dose of 5 to 10 milligrams (mg) for patients with mild to moderate cases of Alzheimer’s disease and in a dose of 10 or 23 mg for patients with moderate to severe Alzheimer’s. Public Citizen is calling for the 23-mg dose to be immediately pulled from the market.

“Data show that the 23-mg dose of donepezil is significantly more toxic than the 10-mg dose,” said Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group. “Combined with its lack of improved clinical benefits, this leads to only one conclusion: that the 23-mg dose should be immediately withdrawn from the market.”

Public Citizen is also asking the FDA to warn doctors and patients against taking 20 mg of the drug (two 10-mg pills) a day, even if Aricept 23 is removed from pharmacy shelves.

Dr. Thomas Finucane, professor of medicine in the Division of Gerontology and Geriatric Medicine at The Johns Hopkins University School of Medicine and staff physician at the Johns Hopkins Bayview Medical Center, stated that “Cholinesterase inhibitors such as Aricept have gained multibillion-dollar success due primarily to two factors: the understandable desperation of those who care for patients with Alzheimer’s disease, and a relentless promotional campaign by drug companies.” Finucane is a co-petitioner with Public Citizen to ban Aricept 23.

“When clinicians consider whether to initiate a therapeutic trial of a largely ineffective drug, the risk of harm should be a prominent consideration,” Finucane said. “The clearly increased risk of harm from Aricept 23-mg compared to Aricept 10-mg is so great, coupled with the lack of any evidence of improved benefit, that I believe it should not have been approved for sale to the families and caregivers of Alzheimer patients.”

The only clinical trial of donepezil submitted to the FDA for approval of the 23-mg dose compared it to the 10-mg dose and failed to prove that the higher dose was more effective. In three of four tests, on either a cognitive or functional level, there was no significant difference between the 10- and 23-mg doses. In the fourth test, the improvement over the 10-mg dose was only two points on a 100-point scale, which is not clinically important, Wolfe said.

Increased adverse effects of the 23-mg dose of donepezil compared to the 10-mg dose include a slowed pulse rate, nausea, vomiting, diarrhea, urinary incontinence, fatigue, dizziness, agitation, confusion and anorexia. Vomiting – which occurred more than 3.5 times as often in patients taking the 23-mg dose than those taking the 10-mg dose – is a particularly dangerous side effect for patients with Alzheimer’s disease because it can lead to pneumonia, massive gastrointestinal bleeding, esophageal rupture and even death, Wolfe said.

Overall, patients taking the 23-mg dose stopped taking the drug because of adverse effects more than twice as often as those taking the 10-mg dose. Additionally, because of the drug’s very long half-life, it can stay in patients’ systems for about two weeks after they stop taking the drug. So, those who suffered adverse effects may not have immediate relief after they stop treatment, Wolfe said.

“With no evidence of an added advantage in benefit to patients, the clear increase in risk should have been more than adequate grounds for denying approval, a conclusion reached by both the FDA medical officer and statistician,” Wolfe said. “It is inexcusable that the FDA approved this higher dose. Its prompt removal would belatedly fulfill the agency’s mission to allow only drugs whose benefits outweigh their risks to be marketed.”

Here is a video of this story.



Comments and questions are welcome.

Monday, May 16, 2011

Niacin - Vitamin B3 and Dementia - Alternative Medicine

Vitamin B3 Reduces Alzheimer's Symptoms, Lesions: Clinical Trial On Nicotinamide Effect In Alzheimer's Patients

ScienceDaily (Nov. 5, 2008) — An over-the-counter vitamin in high doses prevented memory loss in mice with Alzheimer's disease, and UC Irvine scientists now are conducting a clinical trial to determine its effect in humans.

Nicotinamide, a form of vitamin B3, lowered levels of a protein called phosphorylated tau that leads to the development of tangles, one of two brain lesions associated with Alzheimer's disease. The vitamin also strengthened scaffolding along which information travels in brain cells, helping to keep neurons alive and further preventing symptoms in mice genetically wired to develop Alzheimer's.

"Nicotinamide has a very robust effect on neurons," said Kim Green, UCI scientist and lead author of the study. "Nicotinamide prevents loss of cognition in mice with Alzheimer's disease, and the beauty of it is we already are moving forward with a clinical trial."

The study appears online Nov. 5 in the Journal of Neuroscience.

Nicotinamide is a water-soluble vitamin sold in health food stores. It generally is safe but can be toxic in very high doses. Clinical trials have shown it benefits people with diabetes complications and has anti-inflammatory properties that may help people with skin conditions.

Nicotinamide belongs to a class of compounds called HDAC inhibitors, which have been shown to protect the central nervous system in rodent models of Parkinson's and Huntington's diseases and amyotrophic lateral sclerosis. Clinical trials are underway to learn whether HDAC inhibitors help ALS and Huntington's patients.

In the nicotinamide study, Green and his colleague, Frank LaFerla, added the vitamin to drinking water fed to mice. They tested the rodents' short-term and long-term memory over time using water-maze and object-recognition tasks and found that treated Alzheimer's mice performed at the same level as normal mice, while untreated Alzheimer's mice experienced memory loss.

The nicotinamide, in fact, slightly enhanced cognitive abilities in normal mice. "This suggests that not only is it good for Alzheimer's disease, but if normal people take it, some aspects of their memory might improve," said LaFerla, UCI neurobiology and behavior professor.

Scientists also found that the nicotinamide-treated animals had dramatically lower levels of the tau protein that leads to the Alzheimer's tangle lesion. The vitamin did not affect levels of the protein beta amyloid, which clumps in the brain to form plaques, the second type of Alzheimer's lesion.

Nicotinamide, they found, led to an increase in proteins that strengthen microtubules, the scaffolding within brain cells along which information travels. When this scaffolding breaks down, the brain cells can die. Neuronal death leads to dementia experienced by Alzheimer's patients.

"Microtubules are like highways inside cells. What we're doing with nicotinamide is making a wider, more stable highway," Green said. "In Alzheimer's disease, this highway breaks down. We are preventing that from happening.

Abstract of original article:
Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau

Memory loss is the signature feature of Alzheimer's disease, and therapies that prevent or delay its onset are urgently needed. Effective preventive strategies likely offer the greatest and most widespread benefits. Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance memory and synaptic plasticity. We evaluated the efficacy of nicotinamide, a competitive inhibitor of the sirtuins or class III NAD+-dependent HDACs in 3xTg-AD mice, and found that it restored cognitive deficits associated with pathology. Nicotinamide selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1. Nicotinamide also dramatically increased acetylated α-tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability. Reduced phosphoThr231-tau was related to a reduction of monoubiquitin-conjugated tau, suggesting that this posttranslationally modified form of tau may be rapidly degraded. Overexpression of a Thr231-phospho-mimic tau in vitro increased clearance and decreased accumulation of tau compared with wild-type tau. These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD and other tauopathies, and that phosphorylation of tau at Thr231 may regulate tau stability

A general dose of 1,000 milligrams taken three times a day is recommended - this dose is actually the "human equivalent" of the amount given to the mice who recovered from the symptoms of Alzheimer's in the study mentioned above.

All B Vitamins are not the same. Another study showed B vitamins were inneffective which included supplementation with folic acid and vitamins B6 and B12 for 18 months in 409 individuals with mild to moderate Alzheimer's disease. "Participants were randomly assigned to two groups of unequal size; to increase enrollment, 60 percent were treated with high-dose supplements and the remaining 40 percent treated with identical dosages of placebo. A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Cognitive abilities were measured via testing with the Alzheimer Disease Assessment Scale (ADAS-cog).

The researchers found that the ADAS-cog score did not differ significantly between treatment groups, but that symptoms of depression were more common in the high-dose supplement group.

"Our study does not support the treatment of individuals with mild to moderate Alzheimer's disease and normal vitamin levels with B vitamin supplements," the authors conclude." This study did not include vitamin B3m only B6 and B12.

Vitamin B3 (Niacin)
Overview:
Vitamin B3 is one of 8 B vitamins. It is also known as niacin (nicotinic acid) and has 2 other forms, niacinamide (nicotinamide) and inositol hexanicotinate, which have different effects from niacin.

All B vitamins help the body to convert food (carbohydrates) into fuel (glucose), which is "burned" to produce energy. These B vitamins, often referred to as B complex vitamins, also help the body metabolize fats and protein. B complex vitamins are necessary for healthy skin, hair, eyes, and liver. They also help the nervous system function properly.

Niacin also helps the body make various sex and stress-related hormones in the adrenal glands and other parts of the body. Niacin is effective in improving circulation and reducing cholesterol levels in the blood.

All the B vitamins are water-soluble, meaning that the body does not store them.


You can meet all of your body's needs for B3 through diet; it is rare for anyone in the developed world to have a B3 deficiency. In the United States, alcoholism is the prime cause of vitamin B3 deficiency.

Symptoms of mild deficiency include indigestion, fatigue, canker sores, vomiting, and depression. Severe deficiency can cause a condition known as pellagra. Pellagra is characterized by cracked, scaly skin, dementia, and diarrhea. It is generally treated with a nutritionally balanced diet and niacin supplements. Niacin deficiency also results in burning in the mouth and a swollen, bright red tongue.

Very high doses of B3 (available by prescription) have been shown to prevent or improve symptoms of the following conditions. However, taken at high doses niacin can be toxic, so you should take doses higher than the Recommended Daily Allowance only under your doctor's supervision. Researchers are trying to determine if inositol hexanicotinate has similar benefits without serious side effects, but so far results are preliminary.

Precautions:
Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.

High doses (50 mg or more) of niacin can cause side effects. The most common side effect is called "niacin flush," which is a burning, tingling sensation in the face and chest, and red or "flushed" skin. Taking an aspirin 30 minutes prior to the niacin may help reduce this symptom.

At the very high doses used to lower cholesterol and treat other conditions, liver damage and stomach ulcers can occur. Your health care provider will periodically check your liver function through a blood test.

People with a history of liver disease or stomach ulcers should not take niacin supplements. Those with diabetes or gallbladder disease should do so only under the close supervision of their doctor.

Niacin should not be used if you have gout.

Taking any one of the B complex vitamins for a long period of time can result in an imbalance of other important B vitamins. For this reason, it is generally important to take a B complex vitamin with any single B vitamin.
Possible Interactions:

If you are currently taking any of the following medications, you should not use niacin without first talking to your health care provider.

Antibiotics, Tetracycline -- Niacin should not be taken at the same time as the antibiotic tetracycline because it interferes with the absorption and effectiveness of this medication. (All vitamin B complex supplements act in this way and should therefore be taken at different times from tetracycline.)

Aspirin -- Taking aspirin before taking niacin may reduce flushing associated with this vitamin, but should only be done under your doctor's supervision.

Anticoagulants (blood thinners) -- Niacin may make the effects of these medications stronger, increasing the risk of bleeding.

Blood Pressure Medications, Alpha-blockers -- Niacin can make the effects of medications taken to lower blood pressure stronger, leading to the risk of low blood pressure.

Cholesterol-lowering Medications -- Niacin binds bile-acid sequestrants (cholesterol-lowering medications such as colestipol, colesevelam, and cholestyramine) and may decrease their effectiveness. For this reason, niacin and these medications should be taken at different times of the day.

Recent scientific evidence suggests that taking niacin with simvastatin (a drug that belongs to a class of cholesterol-lowering medications known as HMG-CoA reductase inhibitors, or statins), appears to slow down the progression of heart disease. However, the combination may also increase the likelihood for serious side effects, such as muscle inflammation or liver damage.


Diabetes Medications -- Niacin may increase blood glucose (sugar) levels. People taking insulin, metformin, glyburide, glipizide, or other medications used to treat high blood sugar levels should monitor their blood sugar levels closely when taking niacin supplements.

Isoniazid (INH) -- INH, a medication used to treat tuberculosis, may lower levels of niacin in the body and cause a deficiency.

Nicotine Patches -- Using nicotine patches with niacin may worsen or increase the risk of flushing associated with niacin.

Alternative Names:
Inositol hexaniacinate; Niacin; Niacinamide; Nicotinamide; Nicotinic acid

So, maybe I am grasping at straws, but adding a Niacin Supplement seems like it couldn't hurt, and may help. Once again, as with the Pomegranate Juice mentioned in another post, there is some evidence in the research of a recovery, and clearance of the tau protein clumps - at least if you happen to be a genetically-altered mouse. The jury is still out for us human-folk. I am not going to sit around and wait for the verdict. This morning I washed my 1000 mg of B3 down with a nice cold glass of Pomegranate Juice. Something seems to be working. I feel good.

Everything here is my account of what happened to me, or my interpretation of stuff. Every case of FTD is different. Keep in mind as you read this that the person who wrote this has Frontotemporal Degeneration. That would be ME.  Medical Disclaimer.


Comments and questions are welcome.
 

Tuesday, May 10, 2011

Namenda and Aricept

What follows is a little information I found on Namenda(Memantine).
This starter pack increases the dosage over the first month
I started taking it about 2.5 weeks ago using a starter pack I received from my Neurologist. So far I have not had any severe side-effects other than being a little "woozy" at times. From what I can find in the research a combination of Aricept (Donepezil) and Nemanda (Memantine) is more effective than taking either one of them alone. Though some improvement of the symptoms may be expected, the main reason I am taking this combination is to slow the disease progress.

A recent research study was being conducted investigating the effectiveness of the drugs Aricept and Namenda in treating Alzheimer's disease. The study shows that both drugs combine to slow down the degeneration caused by Alzheimer's to its patients. After only a year's treatment, the test subjects indicate a reduction in the progress of the disease with the patients not exhibiting any side-effects from the combination.

The researchers report that the combination of the two drugs is more effective in slowing memory and intellectual function degradation than taking either one of the two drugs or none at all. The study shows how the mix of cholinesterase inhibitors like Aricept, Exelon and/or Razadyne and the drug Namenda (Memantine) taken by patients markedly slows down the rate of memory function decline better than those receiving only a single type of cholinesterase inhibitor or even no drug at all.

In earlier stages of the disease, Alzheimer patients are most commonly treated with a single type of cholinesterase inhibitor. Depending on the diagnosis, it can be either Aricept, Exelon or Razadyne. On the other hand, for advanced stages of the disease are typically treated with the medicine Namenda.

The research was conducted on more than 350 patients in a span of 15 years beginning 1990. The patients were separated into three groups with varying treatments. The first group of more than a hundred patients wasn't treated with any medications while the second group received an FDA approved cholinesterase inhibitor. The last group was treated with the inhibitor augmented with memantine, a drug that aids patients and allows them to think better. Every 2 1 years the patients are given tests that indicate their mental abilities as well as their capability to perform normal daily tasks. Results clearly show a significant decrease in the rate of decline for the third group.

The research was still incomplete. However, since during the time of testing, only cholinesterase inhibitors were the most commonly used and mematine was not tested by itself.



Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial.
Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I; Memantine Study Group.
Source: Department of Psychiatry, University of Rochester Medical Center, Monroe Community Hospital, Rochester, NY 14620, USA. pierre_tariot@urmc.rochester.edu. JAMA. 2004 Jan 21;291(3):317-24.

ABSTRACT:
Memantine is a low- to moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist. Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease (AD) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed.

RESULTS:
The change in total mean (SE) scores favored memantine vs placebo treatment for SIB (possible score range, 0-100), 0.9 (0.67) vs -2.5 (0.69), respectively (P<.001); ADCS-ADL19 (possible score range, 0-54), -2.0 (0.50) vs -3.4 (0.51), respectively (P =.03); and the CIBIC-Plus (possible score range, 1-7), 4.41 (0.074) vs 4.66 (0.075), respectively (P =.03). All other secondary measures showed significant benefits of memantine treatment. Treatment discontinuations because of adverse events for memantine vs placebo were 15 (7.4%) vs 25 (12.4%), respectively.

CONCLUSIONS:
In patients with moderate to severe AD receiving stable doses of donepezil, memantine resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated. These results, together with previous studies, suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD.

Treatment Effect Size of Memantine Therapy in Alzheimer Disease and Vascular Dementia

Smith, Matthew BASc*; Wells, Jennie MSc, MD†; Borrie, Michael MB, ChB

The purpose of this paper is to assess the clinical relevance of the significant results reported in clinical trials of memantine therapy for Alzheimer disease (AD) and vascular dementia. We sought to understand what clinically detectable changes would be evident to the patient with dementia, their caregivers, and the treating physician during a trial of memantine therapy. A literature search was performed on MedLine, PsycInfo, and the Cochrane database. The statistically significant findings from the memantine literature were reviewed using treatment effect size as a measure of clinical meaningfulness. There have been 3 phase 2 studies of memantine in dementia, and 6 phase 3 studies published as of August 1, 2005. Of the 6 published phase 3 trials of memantine in dementia; 2 were in mild-moderate vascular dementia, 1 in mild-moderate AD, 2 in moderate-severe AD, and 1 in severe dementia (both AD and vascular dementia). The most convincing evidence of a clinically meaningful treatment effect of memantine therapy is in the moderate-severe AD patient population. Cognition, as measured by the Severe Impairment Battery, had an effect size of 0.32 and 0.49 in the 2 published trials, indicating a small-to-medium effect of the medication. Global, functional, and behavioral scales also showed a small-to-medium response to memantine.


Everything here is my account of what happened to me, or my interpretation of stuff. Every case of FTD is different. Keep in mind as you read this that the person who wrote this has Frontotemporal Degeneration. That would be ME.  Medical Disclaimer.

Questions and Comments are welcome.