Anti Dementia drugs

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Anti Dementia drugs
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Anti-dementia drugs

• Cholinesterase Inhibitors (aka anti-cholinesterase
  drugs, cholinergic agents).
• Complementary medicines
• Vitamins
• Antipsychotics for treatment of psychotic
  symptoms or agitation/aggression.

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Cholinesterase Inhibitors

• Tacrine (Cognex) - Now seldom prescribed
• Donepezil (Aricept)
• Galantamine hydrobromide (Reminyl)
• Rivastigmine (Exelon)
• TGA approval, now on PBS for mild to moderate
  Dementia of the Alzheimers Type (DAT)
• Stabilise decline.
• Do not halt or reverse disease.

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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.

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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
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Rivastigmine (Exelon). Novartis
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Donepezil (Aricept). Pfizer
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Galantamine Reminyl (Janssen-Cilag)
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Cholinergic pathways
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PBS requirements

• Step 1
• A diagnosis of probable Alzhiemers must be
  confirmed by a specialist (geriatrician or
  psychiatrist)
• Step 2
• Mini Mental State Examination (MMSE) is
  performed.

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Step 3

• If MMSE score 10-24, approval is granted for 1
  months supply with up to 5 repeats.
• If MMSE is gt 24 it is also necessary to perform a
  baseline Alzhiemers Disease Assessment Scales,
  Cognitive sub-scale (ADAS-Cog) or referral to a
  specialist memory disorders unit. The results
  must accompany the application to prescribe.

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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 gt24, 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.

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Summary of trials

• 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

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Side Effects

• Dose related Cholinergic effects
• diarrhoea
• nausea
• vomiting
• anorexia weight loss

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Minimize side effects by

• Start low go slow.

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Complimentary

• Ginkgo Biloba
• 52 week, double blind, placebo controlled trial.
  N309.
• Mild to mod. DAT Multi infarct dementia.
• Small benefits vs placebo.
• Well tolerated
• High drop out rate. (Ernst Pittler, 1999, Le
  Bars, 1997)

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Selegiline Vitamin E

• Each agent delayed progression to moderate to
  severe dementia, loss of basic ADLs, 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)

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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.

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References

• National Prescribing Service. (2001). New
  alzheimer's drugs show only modest benefits.
  National Prescribing Service Newsletter, June 01.
  pdf

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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, Alpha-Tocopherol,
  or Both as Treatment for Alzheimers Disease. New
  England Journal of Medicine, 336(17), 1216-1222.