Transcript Antidementia

Anti Dementia drugs
Anti-dementia drugs
• Cholinesterase Inhibitors (aka anticholinesterase drugs, cholinergic
agents).
• Complementary medicines
• Vitamins
• Antipsychotics for treatment of
psychotic symptoms & or
agitation/aggression.
Cholinesterase Inhibitors
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Tacrine (Cognex) - Now seldom prescribed
Donepezil (Aricept)*
Galantamine hydrobromide (Reminyl)*
Rivastigmine (Exelon)*
*TGA approval, now on PBS for mild to
moderate Dementia of the Alzheimer’s Type
(DAT)
• Stabilise decline.
• Do not halt or reverse disease.
Action
• DAT is characterised by the loss of
the brain neurotransmitter,
acetylcholine.
• Anti-dementia drugs act by
increasing brain levels of
acetylcholine via blockade of the
enzyme that normally breaks it down.
1. Normally acetylcholine
ACh) is broken down by
acetylcholinesterase (AChE)
to chlorine & acetate
2. AChE inhibits this action, increasing amount
& duration of ACh in in synapse
Rivastigmine (Exelon).
Novartis
Donepezil (Aricept). Pfizer
Galantamine Reminyl
(Janssen-Cilag)
Cholinergic pathways
PBS requirements
• Step 1
• A diagnosis of probable Alzhiemer’s
must be confirmed by a specialist
(geriatrician or psychiatrist)
• Step 2
• Mini Mental State Examination
(MMSE) is performed.
Step 3
• If MMSE score 10-24, approval is granted
for 1 months supply with up to 5 repeats.
• If MMSE is > 24 it is also necessary to
perform a baseline Alzhiemer’s Disease
Assessment Scales, Cognitive sub-scale
(ADAS-Cog) or referral to a specialist
memory disorders unit. The results
must accompany the application to
prescribe.
Step 4
• For continued authority to prescribe it is
necessary to demonstrate an
improvement in MMSE score of at least
2 points from baseline.
• For patients >24, a decrease in the
ADAS-Cog score of 4 points or greater
is required.
• The optimal time to perform tests is 4-8
weeks after maximum dose achieved.
Summary of trials
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Only modest improvement overall.
Greatest improvement with higher doses.
Higher doses less well tolerated.
Long term efficacy unknown.
Clinical effectiveness in severe disease
has not been demonstrated.
• Only mildly or moderately affected
individuals were selected for trials
Side Effects
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Dose related Cholinergic effects:
diarrhoea
nausea
vomiting
anorexia & weight loss
Minimize side effects by:
Start low go slow.
Complimentary
• Ginkgo Biloba
• 52 week, double blind, placebo
controlled trial. N=309.
• Mild to mod. DAT & Multi infarct
dementia.
• Small benefits vs placebo.
• Well tolerated
• High drop out rate. (Ernst & Pittler,
1999, Le Bars, 1997)
Selegiline & Vitamin E
• Each agent delayed progression to
moderate to severe dementia, loss of
basic ADL’s, nursing home
placement or death.
• Less benefit with combined therapy.
• Vit E delayed nursing home
placement by 230 days compared to
placebo. (Sano et al, 1997)
References
Ernst, E., & Pittler, M. H. (1999). Ginkgo biloba for
dementia - A systematic review of double-blind,
placebo-controlled trials. Clinical Drug
Investigation, 17(4), 301-308.
Lebars, P. L., Katz, M. M., Berman, N., Itil, T. M.,
Freedman, A. M., & Schatzberg, A. F. (1997). A
Placebo-Controlled, Double-Blind, Randomized
Trial of an Extract of Ginkgo Biloba for
Dementia. Jama: Journal of the American
Medical Association, 278(16), 1327-1332.
References
National Prescribing Service. (2001). New
alzheimer's drugs show only modest benefits.
National Prescribing Service Newsletter, June
01. pdf
References
Sano, M., Ernesto, C., Thomas, R. G., Klauber,
M. R., Schafer, K., Grundman, M., Woodbury,
P., Growdon, J., Cotman, D. W., Pfeiffer, E.,
Schneider, L. S., & Thal, L. J. (1997). A
Controlled Trial of Selegiline, AlphaTocopherol, or Both as Treatment for
Alzheimers Disease. New England Journal of
Medicine, 336(17), 1216-1222.