effectiveness of second generation antipsychotics in dementia related psychosis and agitation l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Effectiveness of second-generation antipsychotics in dementia-related psychosis and agitation PowerPoint Presentation
Download Presentation
Effectiveness of second-generation antipsychotics in dementia-related psychosis and agitation

Loading in 2 Seconds...

play fullscreen
1 / 23

Effectiveness of second-generation antipsychotics in dementia-related psychosis and agitation - PowerPoint PPT Presentation


  • 208 Views
  • Uploaded on

Effectiveness of second-generation antipsychotics in dementia-related psychosis and agitation. Evidence-Based Medicine Seminar October 26, 2006 Brian J. Mickey. Overview. Case presentation Clinical question Literature search results CATIE-AD trial: recent results from phase 1

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Effectiveness of second-generation antipsychotics in dementia-related psychosis and agitation' - amandla


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
effectiveness of second generation antipsychotics in dementia related psychosis and agitation

Effectiveness of second-generation antipsychotics in dementia-related psychosis and agitation

Evidence-Based Medicine Seminar

October 26, 2006

Brian J. Mickey

overview
Overview
  • Case presentation
  • Clinical question
  • Literature search results
  • CATIE-AD trial: recent results from phase 1
  • Group discussion/debate/melee
    • special guests: Chandra Sripada and the Depression Team
case presentation
Ms D is a 75-year-old widowed retired office clerk with a diagnosis of Alzheimer disease who was brought to the Emergency Department (PES) by her 3 daughters in January 2006 for worsening delusions.

About 3 years prior to evaluation, she had presented with short-term memory decline and was diagnosed with probable Alzheimer disease.

About 3 months prior to evaluation, she developed paranoid ideation about men trying to harm her, and one man in particular who rubbed noxious lotion on her back.

Over the prior 2-3 days, her delusions intensified and became more distressing to her and her daughters.

She perceived men outside all night shining lights into the house. She barricaded her doors and started carrying a knife for protection.

She also endorsed mildly depressed mood, low energy, sleep disruption, and daytime somnolence. No manic symptoms.

Case Presentation
case presentation cont d
Past psychiatric history

mild-to-moderate depression for 30 years

antidepressants prescribed by PCP for 8 years

no psychosis, hospitalizations, suicidality

AD diagnosis by neurologist 2003

Substance use history

none

General medical history

probable Alzheimer disease

CAD, MI and stent in July 2005

dyslipidemia

hypertension

asymptomatic meningioma

Medications

escitalopram 20 mg daily

rivastigmine 6 mg qam, 3 mg qhs

memantine 20 mg bid

plavix 75 mg daily

famotidine 20 mg daily

metoprolol 20 mg bid

lisinopril 20 mg daily

pravachol 80 mg qhs

vitamins

Family history

depression (daughters, mother)

no dementias or psychoses

Case Presentation (cont’d)
case presentation cont d5
Social history

lives alone in her own home

husband died in 1990

5 children, daily contact

retired office clerk

daughter is DPOA

Functional assessment

independent in ADLs

cooking less

not driving

unable to manage money

frequently misses medication

Physical examination

T 97.8 HR 49 BP 171/64

no rash

mild tremor, pronator drift, and satelliting on the right

Mental status examination

good grooming and cooperation

alert and attentive to interview

cannot recite days of the week in reverse

oriented to year, month, and city only

recalls 0/3 items at 2 minutes

recalls current but not past US presidents

verbal repetition intact, but word finding difficulties and paraphrasias noted

extensive delusions

visual, auditory, and possibly tactile hallucinations

Case Presentation (cont’d)
case presentation cont d6
Laboratory studies

CBC, comprehensive panel, TSH, UA, UDS were unremarkable

Neuropsychological testing (2003)

verbal IQ lower than predicted

deficits in memory, concentration, attention, calculation, language, visuospatial abilities

MMSE: 21/30

Brain MRI (2003)

1.5-cm enhancing mass near the cribriform plate consistent with meningioma

diffuse volume loss

minimal periventricular FLAIR signal

follow-up scan unchanged in 2004

SPECT perfusion scan (2003)

hypoperfusion to medial temporal lobes bilaterally

milder hypoperfusion to parietal lobes

Case Presentation (cont’d)
clinical question
Patient

Intervention

Comparison

Outcomes

In a 75-year-old patient with AD

do second-generation antipsychotics ...

in comparison to no treatment (placebo) ...

improve symptoms of psychosis and agitation, and improve functioning?

Clinical Question
clinical question8
Clinical Question
  • A related clinical question:What is the risk of serious adverse events when using second-generation antipsychotics in dementia-related psychosis/agitation?

effectiveness

adverse effects

literature search results
Literature search results
  • Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005 Oct 19;294(15):1934-43.
  • Ballard C, Waite J. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003476.
  • Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry. 2006 Mar;14(3):191-210.
  • Ballard C, Howard R. Neuroleptic drugs in dementia: benefits and harm. Nat Rev Neurosci. 2006 Jun;7(6):492-500.
  • Schneider LS et al. for CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006 Oct 12;355(15):1525-38.
literature search results10
Literature search results
  • Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005 Oct 19;294(15):1934-43.
  • Ballard C, Waite J. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003476.
  • Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry. 2006 Mar;14(3):191-210.
  • Ballard C, Howard R. Neuroleptic drugs in dementia: benefits and harm. Nat Rev Neurosci. 2006 Jun;7(6):492-500.
  • Schneider LS et al. for CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006 Oct 12;355(15):1525-38.
catie ad trial
CATIE-AD trial
  • Clinical Antipsychotic Trials of Intervention Effectiveness – Alzheimer Disease
  • NIH sponsored (minimal influence from pharmaceutical industry)
  • Phase 1 compares:
    • risperidone
    • olanzapine
    • quetiapine
    • placebo
  • Phase 2 includes a switch to a different antipsychotic or citalopram
design
Design
  • 421 outpatients with Alzheimer disease and psychosis, aggression, or agitation
  • multi-site, double-blind, placebo-controlled
  • randomized to risperidone, quetiapine, olanzapine, or placebo
  • flexible dosing
  • followed 36 weeks
outcome measures
Outcome measures
  • Primary outcome measure
    • time to discontinuation of treatment (TDT) for any reason
  • Secondary outcome measures
    • number of patients with at least minimal improvement in CGIC at 12 weeks
    • time to discontinuation of treatment due to lack of efficacy
    • time to discontinuation of treatment due to intolerability or adverse events
  • Contrasts with typical outcome measures in industry-sponsored trials
    • e.g., Neuropsychiatric Inventory score at pre-specified time point
    • outcomes not used in routine clinical practice
    • efficacy (pharmaceutical trial) vs effectiveness (real world)
clinical characteristics
Clinical characteristics
  • age: 78 ± 8 yr
  • residence
    • own home 73%
    • family’s home 10%
    • assisted living 10%
  • baseline ratings
    • MMSE 15 ± 6 (0-30)
    • ADAS 35 ± 13 (0-70)
    • NPI 37 ± 18 (0-144)
    • BPRS 28 ± 12 (0-108) delusions 82% hallucinations 49%
  • doses (initial / last)
    • olanzapine 3.2 / 5.5 mg
    • quetiapine 34 / 57 mg
    • risperidone 0.5 / 2.5 mg
primary outcome
Primary outcome
  • No significant differences in TDT for any reason
  • Medians:5.3–8.1 wk
secondary outcome
Secondary outcome
  • TDT due to lack of efficacy
  • Olanzapine was superior to placebo (p<0.001)
  • Risperidone was superior to placebo (p=0.01)
  • Quetiapine did not differ from placebo (p=0.24)
secondary outcome17
Secondary outcome
  • TDT due to intolerability or adverse events
  • Placebo was superior to each antipsychotic medication (p<0.005)
secondary outcome18
Secondary outcome
  • Clinical Global Impression of Change (CGIC) indicating at least minimal improvement
    • olanzapine: 32%
    • risperidone: 29%
    • quetiapine: 26%
    • placebo: 21%
    • no significant differences between treatments (p=0.22)
possible discussion points
Possible discussion points
  • Implications for my patient?
  • Interpretation of the results more generally?
  • Effects of population heterogeneity?
  • Psychosis vs agitation vs aggression?
  • Quetiapine underdosed?
  • What study should be done next?