Treatment for Behavioral and Psychological Symptoms of Alzheimer’s Disease

1. Treatment for Behavioral and Psychological Symptoms of Alzheimer’s Disease Mindy Wasson April 12, 2007 Mr. Powdrill

2. Alzheimer’s Disease (AD) • Definition: “ a progressive neurodegenerative disease characterized by a loss of function and death of nerve cells in several areas of the brain.”

3. Statistics in the U.S. • Prevalence: • affects 4.5 million people • accounts for 90% of all cases of neurodegenerative diseases. • Expected to affect as many as 16 million by 2050 • Mortality: • over 100,000 die each year • 4th leading cause of death in adults

4. Symptoms of AD • Cognitive: • memory loss, language disturbances • Functional: • difficulty dressing, difficulty eating, incontinence • Behavioral/Psychological: • agitation, aggression, delusions, hallucinations

5. Behavioral and Psychological Symptoms of AD (BPSD)

6. Cumulative prevalence: since onset of illness Point prevalence: over the last month Community sample of 362 people with dementia ___________________ 80% 62% BPSD are very common

7. Why are BPSD important? • Excess disability • Increased hospitalization • Premature institutionalization • Suffering for patient and caregiver • Substantial increase in financial costs • Increased risk for abuse

8. Overview of Treatment Strategy • Address underlying medical/medication-related factors • Caregiver education/training • Non-pharmacological interventions • Always 1st choice • Pharmacological interventions • ONLY if non-pharmacological behavioral interventions fail

9. Medical factors: Vision/hearing loss Acute/chronic pain Malnutrition Dehydration Urinary retention Urinary incontinence Constipation Infection Medications: Anticholinergics Opiates Sedative-hypnotics Antidepressants Beta-blockers Antipsychotics Benadryl Quinolones Medical and Medication-related factors

10. 3 R’s: Repeat Reassure Redirect Used to stress the importance of patience and coolness during interactions and redirection Also to remind the difficulty of patient’s situation and the need to be supportive and not demanding ABC’s Antecedent Must assess multitude of potential causes of BPSD Behavior Assess reactions of patient to causes found and develop a theme and appropriate plan of action Consequences Assess the severity of behavior; positive/negative reinforcement Caregiver Education and Support

11. Non-pharmacological Interventions • Careful evaluation of environment may be a clue to underlying cause of BPSD: • Consistent and pleasant environment: • Speak slowly, keep commands simple, use gestures • Gentle touch, soft lighting, music, calm colors, orientation clues, plants • Consistent schedule: • Stable routine; change must be gradual • Promote sleep: increase daytime activity with supervised walks; spend time outside; gardening; molding clay

12. Pharmacological Interventions • In general, modest benefits with significant potential for side effects • Categories • Atypical antipsychotics- best evidence • Antidepressants- some evidence • Cognitive Enhancers- some evidence • Anticonvulsants- mixed results • Typical antipsychotics- not used • Sedative-hypnotics- serious side effects • All choices are off-label usages

13. Efficacy of Atypical Antipsychotics • Primary off-label treatment choice • Up to 45% people with dementia are taking antipsychotics • small effect on behavioral symptoms • NNT=6 patients must be treated for 1 to respond • Response usually in first 2-4 weeks • Effects can be variable; high rates of discontinuation

14. Atypical Antipsychotics: SAFETY • Extrapyramidal symptoms • Diabetes and dyslipidemia* • Cerebrovascular adverse events (CVAEs)* • Mortality* • Cognitive Impairment • Fails • Sedation • QT prolongation

15. FDA Warnings: Atypical Antipsychotics • CVAEs (Apr. 2003, Jan. 2004): • Risperidone: • Meta-analysis of elderly patients with AD (n=1779) • significantly higher incidence of CVAEs with risperidone versus placebo • Overall odds ratio was 3.32 • 45% of events were considered serious/life-threatening

16. FDA Warnings: Atypical Antipsychotics • Mortality (April 2005): • Meta-analysis of 17 placebo-controlled clinical trials (n=5106) among elderly patients with dementia • assessed incidence of mortality for aripiprazole, olanzapine, risperidone, quetiapine • Pooled 4.5% incidence of mortality for atypical antipsychotics compared to 2.6% for placebo

17. FDA Warnings • FDA concluded that atypical antipsychotics should no longer be used among elderly patients with dementia

18. So what should be used? Very few well designed clinical trials; mostly retrospective and contradictory: • Antidepressants: modest benefits, but safer • Anticonvulsants: questions about efficacy, tolerability, and drug-drug interactions • Cognitive enhancers: modest benefits, patient should probably already be on these anyway • Sedative-hypnotics: risks generally outweigh benefits

19. Conclusions • AD is prevalent, deadly, and on the rise • BPSD has been seen up in to 80% patients with AD • Major negative impact on patients, families, and caregivers • Non-pharmacological: Evidence-based interventions can be very effective even in extreme situations of distress • ALWAYS 1st choice; requires persistence and training to be fully effective • Continue interventions even when pharmacological treatment is indicated

20. Conclusions • Pharmacological: • Antipsychotics have been primary treatment choice for over a decade • Are unsafe and only modestly effective • Should only be used when immediate harm to patient or others exists; NEVER as 1st line • Best treatment option is now unclear • Need well-designed clinical trials assessing effectiveness and safety of non-antipsychotic choices

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23. Questions????