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Quetiapine treatment in
Alzheimer’s disease
Diana Paleacu, MD
Neurology Service and Memory Clinic
Abarbanel Mental Health Center
Affiliated to the Sackler School of Medicine
Tel Aviv University
Progression of symptoms in AD
Pattern of symptoms over time in patients with AD
Lovestone & Gauthier 2001
Behavioral and Psychological
Symptoms of Dementia
(BPSD)





Include disorders of behavior, mood, thought
content and perception (Burns et al, 1990)
Are common (90% - Ballard et al, 2002)
Cause distress to patients and caregivers
Main cause of over institutionalization and
medication (Shah, 1999)
Defined operationally by Jeste DV, Finkel SI.
Psychosis of Alzheimer’s Disease and related
dementias. Diagnostic criteria for a distinct
syndrome, Am J Geriatr Psychiatry 2000;
8(1):29-34
BPSD Treatment

Antipsychotics
 Antiepileptics
 Benzodiazepines
 AChI
Vs.

Non-pharmacological treatment
UK Committee of Safety of
Medicines (March 2004)
Risperidone and Olanzapine shold not be
used in the treatment of BPSD because of
increased risk of strokes w/both drugs and
increased risk of mortality w/olanzapine
 X3 CVA for risperidone (3.3%) vs Placebo
(1.2%)
six studies
 X4 CVA for olanzapine (1.4%) vs Placebo
(0.4%)
 mortality in OL group: 3.5% vs 1.5%
Quetiapine
 Novel
SGA
 higher affinity for the serotonin 5-HT1a
and 5-HT2 receptor than the dopamine D1
and D2 receptors
 It appears to have a selective preferential
influence on the mesolimbic and
mesocortical systems
 minimal effects on the nigrostriatal
dopamine system
 minor activity upon the tubero-infundibular
dopamine system
Quetiapine treatment of agitation in
patients with Alzheimer's disease.
Mintzer J, Zhong K, Tariot P, Minkwitz MC,
Devine NA
In: New Research Abstracts of the 158th
Annual Meeting of the American Psychiatric
Association, 21-26 May, 2005, Atlanta, GA,
USA. Abstract NR882:328.
Quetiapine Treatment for behavioral and
psychological symptoms of dementia in
Alzheimer’s disease patients: a six weeks
double blind placebo controlled study
D. Paleacu, MD 1, Y. Barak, MD, MHA 2, I.
Mirecky, MD 2, D. Mazeh, MD 2
1 Neurology Service and Memory Clinic
2 Psychogeriatric Department
Abarbanel Mental Health Center, Bat-Yam,
Israel, Affiliated with the Sackler School of
Medicine, Tel Aviv University, Israel
Patients and Methods
 40 AD
patients w/BPSD
 Trial duration:6 weeks
 Recruited during: March 2003-March 2004
 2 arms
 Starting dose 25mg/day – 150 mg/day up
to effect or S/E
 Use NPI and CGIC as primary outcome
measures
Patients’ Flow Chart
44 AD patients screened
4 patients disqualified
due to:
active ischemic heart
disease (3) and
concomitant
malignancy (1)
40 patients randomized
20 patients:
quetiapine
Completed
12
Discontinued
8
20 patients:
placebo
Completed
15
Discontinued
5
FIGURE 1: MMSE CHANGES BETWEEN VISIT 0 AND VISIT 8
BY TREATMENT GROUP
0.25
N.S.
MMSE CHANGES
0.2
0.15
0.1
0.05
0
P
S
FIGURE 5: NPI CHANGES BETWEEN VISIT 8
TO VISIT 0, BY TREATMENT GROUP
P=0.050 P=0.080
NPI CHANGES
0
-2
-4
-6
P
S
-8
DEL
HAL
AGIT ANX
EUPH APATDISIN
IRRIT
AMBNIGHT APPET
DEP
FIGURE 2: CGIC CHANGES BETWEEN VISIT (3,4,5,6,7,8)
TO VISIT 2, BY TREATMENT GROUP
CGIC CHANGES
0
-0.5
N.S.
-1
P=0.059
-1.5
N.S.
P
N.S.
N.S.
S
P=0.025
-2
WEEK1
WEEK2
WEEK3
WEEK4
WEEK5
WEEK6
CGIC CHANGES FROM BASELINE, BY STUDY DRUG
6

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Study drug
P 
S
CGIC
5
4




3







4
5
6
2



1
0
1
2
3
Visit Number
7
8
FIGURE 3: AIMS CHANGES BETWEEN VISIT (4,6,8)
TO VISIT 2, BY TREATMENT GROUP
0.6
P=0.090
P
AIMS CHANGES
0.4
0.2
N.S.
N.S.
0
-0.2
-0.4
-0.6
-0.8
WEEK 2
WEEK 4
WEEK 6
S
FIGURE 4: SAS CHANGES BETWEEN VISIT (4,6,8)
TO VISIT 2, BY TREATMENT GROUP
1
SAS CHANGES
P=0.070
P
P=0.080
N.S.
0.5
0
-0.5
-1
-1.5
WEEK 2
WEEK 4
WEEK 6
S
To treat or not to treat… BPSD
 60%
of patients vs. 40% on placebo have
a significant response to neuroleptics
 Cochrane review on HPL (Lonergan
2003): aggression responds better
 Flaws in Evidence re.
Risperidone/Olanzapine trials some
patients had CV risk factors to start with
 no clear evidence of increased risk for
young patients
The Future…

1.
2.
3.
till we get precise data from larger pooled
studies in elderly we need to:
consider first non-pharmacological
interventions
use AChI and memantine for BPSD
discuss these issues with the CG and
weigh up the risks and the benefits
CATIE-AD
CLINICAL ANTIPSYCHOTIC TRIAL OF INTERVENTION
EFFECTIVENESS

9 MONTHS (Jan-Oct 2004)
 AD outpatients
 Ris, Ol, Quet vs. Placebo + citalopram
 Randomized and double blind
 421 patients
 Efficacy and symptom related outcomes
 Safety and tolerability
 Caregiver related assessments
 Cost-effectiveness, service utilization and health
outcomes
“The debate is really about defining
where the threshold for prescribing
neuroleptics to people with dementia
should lie, rather than whether we
should use or not use these drugs at
all"
Ian McKeith, International Psychogeriatrics,
2005, 17(1), 22-25