Treating Psychiatric and Behavioural Symptoms in People with Alzheimers Disease

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Treating Psychiatric and Behavioural Symptoms in
People with Alzheimers Disease

• Clive Ballard
• Professor of Age Related Diseases, Kings College
  London
• and
• Director of Research, Alzheimers Society

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Short term prescribing

• Up to 3 months

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Non AD dementias

• Vascular dementia (VaD) Some VaD patients in 2
  of the risperidone studies, but no separate
  analysis and no specific trials of VaD
• DLB/PDD only 1 RCT (with quetiapine), showing
  no significant benefit. Serious potential
  concerns re neuroleptic sensitivity
• Marked need for treatment studies examining
  treatment of neuropsychiatric symptoms in non-AD
  dementias

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Risperidone for Neuropsychiatric Symptoms
Efficacy
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Schneider et al 2006 Aripiprazole
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Risperidone for Neuropsychiatric Symptoms
Adverse Outcomes
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Mortality and neuroleptics in people with
dementia

• FDA meta-analysis of 17 placebo-controlled
  trials of atypical neuroleptics in AD
  significant 1.7-fold increase in mortality with
  neuroleptics
• Schneider et al, JAMA 2005 meta-analysis of 15
  trials, with significant 1.54-fold increased
  mortality risk, with absolute increase of 1
• Mortality risk less clear from case register
  studies
• Yang et al, NEJM 2005 mortality risk even higher
  with typical neuroleptics

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Schneider, Am J Ger Psych 2006
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Longer term prescribing

• 6-12 months

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AGIT-AD Ballard et al 2005 BMJ
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CATIE Schneider et al 2006 NEJM
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CGIC improvement at 12 weeks 32 olanzapine 26
quetiapine group, 29 risperidone group, 21
placebo group (P0.22).
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Neuroleptic withdrawal studies

• Bridges-Parlet et al, 1997
• Cohen-Mansfield et al, 1999
• Ballard et al, 2002
• RCT studies, 6 weeks3 months
• Total gt180 participants
• No significant worsening of BPSD in any of the
  studies

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DART-AD Ballard, Jacoby, Margallo-Lana et al 2008

• 12 month placebo controlled neuroleptic
  withdrawal trial for Nursing home residents with
  dementia on neuroleptics for gt 3 months (most
  participants 12-24 months)
• Primary outcome at 6 months
• Follow-up for up to 54 months to examine
  mortality
• 165 participants randomized, 102 completed 6
  months, 109 included in analysis with imputation

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Change from Baseline to 6 months
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Change from Baseline to 6 months
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Month 12
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Real Life Prescribing
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Psychotropic drugs in NH

• 40-60 people with dementia in NH are taking nlps
  
• (eg McGrath, , Thacker, Lana, Draper)

Agit (n72) 38 (53) 10 (14) 17 (24) 3 (4)
No. patients ()
Drugs Neuroleptics Benzodiazepines Antidepressant
s Other psych
None(n13) 4 (31) 0 2 (15) 1 (8)
Del(n28) 13 (46) 4 (14) 6 (21) 1 (4)
Dep(n35) 16 (46) 5 (14) 13 (37) 0
Ballard et al 2001
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FITS Baseline Prescribing Data

• 12 nursing homes, 348 people with dementia.
• 168 (48) prescribed 1 antipsychotic, 22 (6)
  prescribed 2 antipsychotics, 3 (1) prescribed 3
  antipsychotics
• Average annual cost for each nursing home 13,
  189.
• Extrapolated UK annual cost 80M

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Illbeing (N-112)
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Other Pharmacological Treatments
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Neuropsychiatric Symptoms in AD Alternative
Pharmacological Therapies
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CALM-AD NEJM 2007 Analysis of change in outcome
from baseline to 12 weeks
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Aromatherapy, Herbal Remedies and Food Supplements
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Evidence for Psychological Therapies

• 1,632 references, 162 were included. (Livingston
  2005).
• Few RCT studies for specific treatments

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Validation Therapy

• Pragmatic therapy aiming to improve
  communication, provide empathy, restore dignity
  and respect the individuals reality
• Usually delivered in groups with elements such as
  communication, activities, singing and music
• Cochrane review (Neal 2008)
• 3 trials116 patients, but difficult to combine in
  meta-analysis
• Validation significantly greater improvement in
  behaviour than usual care (P0.007), but
  equivalent to social contact.

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Standardized tailored psychological treatment

• Cohen-Mansfield 2007 (n167) Placebo controlled
  trial of personalized non-pharmacological
  interventions for 4 hours over days resulted in
  significant reduction in agitation (p0.002)
• Cohen-Mansfield 1997 (N58) Placebo controlled
  trial of social interaction, music or simulated
  presence resulted in significant 25 reduction in
  abnormal vocalizations over 6 weeks

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c
FITS TRIAL
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Conclusion

• Atypical antipsychotics have short term efficacy
  for the treatment of aggression, but have
  considerable adverse effects
• There are several candidate alternative
  pharmacological therapies, but better evidence is
  urgently needed
• Aromatherapy with melissa or lavender are
  evidence based alternatives
• Psychological therapies are a safe alternative,
  with emerging evidence of efficacy