Professional Documents
Culture Documents
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
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
patients: 20 patients: 20
quetiapine placebo
0.25
P S
N.S.
0.2
MMSE CHANGES
0.15
0.1
0.05
0
FIGURE 5: NPI CHANGES BETWEEN VISIT 8
TO VISIT 0, BY TREATMENT GROUP
P=0.050 P=0.080
0
2-
NPI CHANGES
4-
6-
P S
8-
DEL HAL AGIT ANX EUPH APATDISIN IRRIT AMB NIGHT APPET DEP
)FIGURE 2: CGIC CHANGES BETWEEN VISIT )3,4,5,6,7,8
TO VISIT 2, BY TREATMENT GROUP
0
CGIC CHANGES
0.5-
.N.S
1-
P=0.059
.N.S
1.5- .N.S
.N.S
P S P=0.025
2-
WEEK1 WEEK2 WEEK3 WEEK4 WEEK5 WEEK6
CGIC CHANGES FROM BASELINE, BY STUDY DRUG
6
Study drug
5 P S
4
CGIC
3
2
0
1 2 3 4 5 6 7 8
Visit Number
)FIGURE 3: AIMS CHANGES BETWEEN VISIT )4,6,8
TO VISIT 2, BY TREATMENT GROUP
0.6
P=0.090 P S
0.4
AIMS CHANGES
0.2 .N.S
.N.S
0
0.2-
0.4-
0.6-
0.8-
WEEK 2 WEEK 4 WEEK 6
)FIGURE 4: SAS CHANGES BETWEEN VISIT )4,6,8
TO VISIT 2, BY TREATMENT GROUP
1
P=0.080 P S
P=0.070
.N.S
0.5
SAS CHANGES
0.5-
1-
1.5-
WEEK 2 WEEK 4 WEEK 6
P S
akathisia 1
parkinsonism 1 1
tremor 1
diarrhea 1
dizziness 1
dry mouth 1
edema 1
falls 2
headaches 1
sedation 1
confusion UTI 1
ALL 8 5
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
till we get precise
data from larger pooled studies in elderly
we need to:
2. consider first non-pharmacological
interventions
3. use AChI and memantine for BPSD
4. discuss these issues with the CG and
weigh up the risks and the benefits
CATIE-AD
CLINICAL ANTIPSYCHOTIC TRIAL OF INTERVENTION
EFFECTIVENESS
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