Utilizzo di antipsicotici nelle modificazioni comportamentali nel paziente con demenza

1. Treatment
of
behavioral
symptoms
related
to
demen4a
Behavioral
symptoms
in
Alzheimer
disease
(AD)
and
other
types
of
demen8a
are
extremely
common
and
o;en
much
more
troubling
than
amnes8c
symptoms.
This
topic
will
review
the
causes
and
treatment
of
behavioral
disturbance
and
symptoms
related
to
demen8a

2. An4psycho4c
drugs
Atypical
neurolep4cs
have
been
the
agents
of
choice
for
trea4ng
hallucina4ons
in
pa4ents
with
demen4a.
However,
these
drugs
may
increase
mortality,
and
are
not
approved
for
the
treatment
of
behavioral
disorders
in
pa8ents
with
demen8a
by
the
US
Food
and
Drug
Administra8on
(FDA).
Nonetheless,
their
benefits
o;en
s8ll
outweigh
their
risks
in
pa8ents
with
demen8a
when
treatment
of
hallucina8ons
and
delusions
is
cri8cal.
In
the
absence
of
other
effec4ve
agents,
we
con4nue
to
use
them
cau4ously,
a>er
informing
the
pa4ents
and
families
of
the
poten4al
risks
Typical
an4psycho4cs
—
A
systemic
review
of
typical
an8psycho8cs
included
two
meta-­‐analyses
of
12
trials
plus
two
addi8onal
studies
of
haloperidol,
thioridazine,
thiothixene,
chlorpromazine,trifluoperazine
and
acetophenazine,
and
concluded
that,
in
the
aggregate,
there
was
no
clear
evidence
of
benefit
for
these
agents
in
pa8ents
with
demen8a
[42].
A
Cochrane
review
concluded
that
haloperidol
may
help
control
aggression,
but
not
other
neuropsychiatric
manifesta8ons
of
demen8a
[43].
No
trials
compared
agents
with
one
another
Atypical
an4psycho4cs
—
These
agents
include
clozapine,
olanzapine,
risperidone,
and
que4apine
and
have
been
somewhat
more
extensively
studied.
Two
independently
conducted
systema8c
reviews
have
concluded
that
these
agents
have,
at
most
modest
efficacy
[42,44].
Of
seven
trials
studied,
four
found
a
sta8s8cally
significant
benefit
for
the
primary
endpoint
with
olanzapine
or
risperidone;
there
were
no
studies
of
clozapine
and
que8apine
for
this
indica8on
at
the
8me
of
this
analysis.

3. CLASSIFICAZIONE
DEI
FARMACI
ANTIPSICOTICI
IN
TIPICI
ED
ATIPICI
TIPICI
ATIPICI
Feno8azine
Clorpromazina
-­‐
Largac4l
Benzamidi
Promazina
Talofen
Sulpiride
–
Dobren
Tioridazina
-­‐
MellereQe
-­‐Melleril
Dibenzoxazepine
Flufenazina
-­‐
Anatensol,
Moditen
Depot
Clozapina
-­‐
Leponex
Tioxanteni
Olanzapina
-­‐
Zyprexa
Zuclopen8xolo
-­‐
Clopixol
Altri
compos8
Bu8rrofenoni
Risperidone
-­‐Risperidal
Aloperidolo
-­‐
Haldol
-­‐
Serenase
Zipraxidone
Difenilbu8lpiperidine
Pimozide
-­‐
Orap

4. Side
effects
The
choice
of
specific
an8psycho8c
drug
used
to
treat
hallucina8ons
is
driven
by
drug
side
effects
such
as
seda8on
or
extrapyramidal
disturbances.
The
older
low
potency
typical(conven4onal)
neurolep4cs
(eg,
chlorpromazine
and
thioridazine)
are
highly
seda8ng,
and
their
an8cholinergic
ac8vity
can
worsen
memory
and
cogni8on.
High
potency
neurolep8cs
(eg,
haloperidol
and
fluphenazine)
are
associated
with
an
o;en
unacceptable
incidence
of
extrapyramidal
side
effects.
In
a
trial
of
haloperidol,
for
example,
there
was
a
high
rate
of
extrapyramidal
side
effects
and
decline
in
cogni8ve
func8on
even
at
rela8vely
low
doses
of
1
to
5
mg.Intravenous
haloperidol
has
been
associated
with
clinically
significant
QT
prolonga8on
requiring
addi8onal
precau8ons
regarding
its
use.
While
the
atypical
neurolep4cs
are
perceived
to
have
a
lower
incidence
of
adverse
effects,
this
may
be
true
only
with
low
doses.
Systema8c
reviews
and
clinical
trials
find
that
adverse
events
with
these
agents
in
pa8ents
with
demen8a
are
common
and
dose
related.
These
include
extrapyramidal
symptoms,
confusion,
somnolence,
and
falls.
The
addi8onal
risk
of
agranulocytosis
with
clozapine
and
the
necessity
for
frequent
blood
tests
make
this
agent
less
a`rac8ve.

5. Mortality
risk
The
US
Food
and
Drug
Administra8on
(FDA)
reported
in
a
public
health
advisory
that
the
use
of
second
genera8on
an8psycho8c
medica8ons,
aripiprazole,
olanzapine,
que4apine,
and
risperidone,
for
the
treatment
of
behavioral
symptoms
in
elderly
pa8ents
with
demen8a
is
associated
with
increased
mortality
[49,50].
Their
findings
were
confirmed
in
an
independently
conducted
meta-­‐
analysis,
as
well
as
a
subsequent
randomized,
placebo-­‐controlled
study.
The
reported
odds
ra8o
for
increased
mortality
in
these
analyses
ranged
from
1.54
to
1.7.

6. Clinical
use
Given
the
risk
of
increased
mortality
associated
with
the
use
of
atypical
neurolep8cs
in
elderly
pa8ents
with
demen8a
,
we
reserve
their
use
for
pa8ents
who
have
neuropsychiatric
symptoms,
par4cularly
psychosis,
that
are
severe
and
debilita4ng
and
inform
pa4ents
and
families
of
the
risks.
There
is
o;en
no
good
alterna8ve.
Somnolence
is
also
concern
with
all
of
these
agents,
and
may
be
dose
limi8ng.
Olanzapine
(Zyprexa
cpr
2.5
,
5,
10
mg
CLASSE
A
NOTA
A8
PIANO
TERAPEUTICO)
can
be
started
at
a
dose
of
2.5
mg
daily
and
4trated
up
to
a
maximum
of
5
mg
twice
a
day.
This
drug
appears
to
be
at
least
modestly
effec8ve
for
trea8ng
the
neuropsychiatric
symptoms
of
demen8a
in
pa8ents
with
AD
or
vascular
demen8a.
The
incidence
of
extrapyramidal
symptoms
is
low
at
this
dose.
Que4apine
(Seroquel
cpr
25,
50,
100,
150,
200,
300,
400
mg
CLASSE
A
NOTA
A8
PIANO
TERAPEUTICO)
is
an
alterna8ve,
star8ng
at
a
dose
of
25
mg
at
bed4me
and
4tra4ng
up
to
a
maximum
of
75
mg
twice
a
day.
There
is
li`le
data
regarding
the
effec8veness
of
que8apine
in
this
seeng.
Risperidone
(Risperdarl
cpr1,2,3,4,mg
CLASSE
A
NOTA
A8
PIANO
TERAPEUTICO)
at
no
more
than
1
mg
daily
also
appears
to
be
at
least
modestly
effec8ve,
but
higher
doses
are
associated
with
increased
side
effects.
Treatment
should
be
maintained
only
if
benefits
are
apparent,
and
discon8nua8on
should
be
a`empted
at
regular
intervals.

7. SUMMARY
AND
RECOMMENDATIONS

8. Neuropsychiatric
symptoms
are
common
in
demen8a
and
contribute
to
nursing
home
admission
and
caregiver
stress.
When
a
pa8ent
develops
neuropsychiatric
symptoms,
the
first
step
is
to
rule
out
and
treat
a
medical
cause
or
superimposed
delirium

9. Environmental,
behavioral,
and
other
nonpharmacologic
therapies
can
be
effec8ve
in
this
popula8on
and,
when
appropriate,
are
preferred
over
medica8ons,
which
have
a
high
rate
of
adverse
effects.
Cholinesterase
inhibitors
do
not
produce
clinically
significant
improvement
in
neuropsychiatric
symptoms
in
pa8ents
with
demen8a.
However,
many
such
pa8ents
are
s8ll
treated
with
these
drugs
because
of
modest
improvement
in
cogni8on.
An8psycho8c
agents
have
limited
efficacy
and
are
associated
with
increased
mortality
in
pa8ents
with
demen8a.
We
suggest
the
use
of
low
doses
of
olanzapine
or
que8apine
in
pa8ents
with
severe,
disabling
symptoms
a;er
informing
families
of
the
mortality
risk
(Grade
2B).
Short
term
use
when
possible,
with
regular
reassessments
of
risks
and
benefits,
is
advised.
A
trial
of
selec8ve
serotonin
reuptake
inhibitors
(SSRIs)
is
suggested
for
the
treatment
of
depression
in
Alzheimer
disease
(Grade
2C).
Citalopram
is
o;en
used
because
of
its
possible
addi8onal
benefits
for
neuropsychiatric
symptoms.
Sertraline
is
a
well
studied
alterna8ve
to
citalopram.
A
trial
of
trazodone
may
also
be
considered
to
treat
psycho8c
symptoms,
especially
when
they
interfere
with
sleep.
Tricyclics
should
be
avoided
because
of
side
effects
and
drug
interac8ons.
Agita8on
may
be
due
to
unrecognized
depression
and
respond
to
an
SSRI.
Because
of
the
risk
of
side
effects
with
long-­‐term
use,
we
recommend
reserving
benzodiazepines
for
acute
stressful
episodes