THERAPEUTIC
STRATEGIES
DRUG DISCOVERY
TODAY
Treatment
of
first-episode
schizophrenia:
pharmacological
and
neurobiological
aspects
Alkomiet
Hasan
*
,
Thomas
Wobrock,
Daniela
Reich-Erkelenz,
Peter
Falkai
Department
of
Psychiatry
and
Psychotherapy,
Georg
August
University
Go¨ttingen,
Von-Siebold-Strasse
5,
D-37075
Go¨ttingen,
Germany
The
treatment
and
understanding
of
first-episode
schi-
zophrenia
belongs
to
the
greatest
challenges
in
clinical
psychiatry
and
psychiatric
research.
Antipsychotic
drugs
revolutionised
the
therapy
of
schizophrenia
since
their
first
introduction
in
the
1950s.
However,
there
are
still
unsolved
questions
about
an
evidence-based
and
improved
treatment
of
first-episode
patients,
which
neurobiological
and
clinical
studies
can
help
answering.
Section
editors
:
Diana
Kristensen
–
Department
of
Psychiatry,
Hvidovre
University
Hospital,
Brøndby,
Copenhagen,
Denmark
Mikkel
Myatt
–
Psykiatrisk
Center
Glostrup,
Copenhagen
University,
Glostrup,
Copenhagen,
Denmark
Introduction
Schizophrenia
is
still
the
most
serious
psychiatric
condition
affecting
all
areas
of
the
patient’s
life
and
leading
in
most
cases
to
a
chronic
disease
course.
Therefore,
the
development
of
effective
therapeutic
strategies,
especially
in
the
beginning
of
the
disease,
is
one
of
the
most
important
challenges
in
psychiatric
research.
However,
most
of
the
available
antipsy-
chotic
drugs
for
the
treatment
of
schizophrenia
have
not
been
investigated
to
a
great
extent
in
first-episode
schizo-
phrenia
patients:
even
today,
only
unsatisfying
evidence
exists
about
the
arrangement
of
a
conclusive
therapy
with
the
currently
available
antipsychotic
drugs.
This
short-review
will
focus
on
the
currently
available
and
evidence-based
treatment
strategies
in
first-episode
schizo-
phrenia
and
will
address
problems
in
transferring
findings
from
chronically
ill
to
first-episode
patients.
Furthermore,
we
will
provide
some
treatment
recommendations
according
to
the
recent
national
and
international
guidelines
and
discuss
new
treatment
options
which
might
become
available
for
future
clinical
use.
Diagnosis
and
disease
course
Research
on
first-episode
schizophrenia
patients
raises
the
question
about
how
to
exactly
define
the
first-episode.
In
most
studies
and
in
clinical
practice,
the
beginning
of
the
first-episode
is
defined
by
the
onset
of
the
first
prominent,
long-lasting
psychotic
symptoms
identifiable
by
the
patient
or
outsiders
[
1,2
].
However,
the
definition
of
first-episode
schizo-
phrenia
varies
and
overlaps
with
other
terms
like
recent-
onset
schizophrenia:
this
may
explain
diagnostic
uncertainties
and
variable
findings
in
clinical
and
experimental
trials.
Furthermore,
the
duration
of
the
untreated
illness
(DUI,
time
from
the
onset
of
non-specific
symptoms
till
treatment)
and
duration
of
the
untreated
psychosis
(DUP,
time
from
the
first
onset
of
productive
psychotic
symptoms
till
treatment)
represent
important
aspects
in
treatment
prognosis.
Different
studies
reveal
long
DUIs
(mean:
more
than
4.5
years)
and
DUPs
(mean:
more
than
2
years)
before
a
first-episode
schizophrenia
is
diagnosed
[
2–4
].
A
prolonged
DUI/DUP
is
associated
with
a
poorer
outcome
of
the
first-episode
schizo-
phrenia,
a
less
complete
recovery
and
an
increased
risk
for
a
relapse
[
5
].
A
short
duration
of
DUP
was
found
to
be
Drug
Discovery
Today:
Therapeutic
Strategies
Vol.
8,
No.
1–2
2011
Editors-in-Chief
Raymond
Baker
–
formerly
University
of
Southampton,
UK
and
Merck
Sharp
&
Dohme,
UK
Eliot
Ohlstein
–
GlaxoSmithKline,
USA
Treatment
of
schizophrenia
*Corresponding
author:
A.
Hasan
(
ahasan@gwdg.de
),
(
a.hasan@ion.ucl.ac.uk
)
1740-6773/$
ß
2011
Elsevier
Ltd.
All
rights
reserved.
DOI:
10.1016/j.ddstr.2011.09.003
31
associated
with
a
better
response
to
antipsychotic
treatment
in
meta-analyses
and
systematic
reviews
[
6
].
Therefore,
one
key
feature
of
a
modern
and
successful
treatment
of
first-
episode
schizophrenia
is
to
shorten
the
time
between
symp-
tom
onset
and
diagnosis
and
to
start
antipsychotic
treatment
as
soon
as
the
diagnosis
of
first-episode
schizophrenia
is
confirmed
[
5
].
The
question,
whether
to
treat
patients
during
the
prodromal
phase
before
explicitly
diagnosing
a
first-epi-
sode
schizophrenia
or
not
is
subject
of
ongoing
discussions
(see
[
7,8
]).
However,
because
of
low
transition
rates
(below
20%
[
9
])
and
only
few
randomized
clinical
trials,
currently
no
specific
evidence-based
treatment
for
the
prodromal
phase
can
be
recommended.
First-generation
antipsychotics
or
second-generation
antipsychotics?
Since
the
first
introduction
of
antipsychotic
drugs,
a
magni-
tude
of
randomized
clinical
trials
provided
strong
evidence
for
their
efficacy
in
the
treatment
of
psychotic
symptoms
in
first-episode
and
multi-episode
schizophrenia
patients
(for
detailed
reviews
see
[
5,10
]).
With
regard
to
the
side
effect
profile
and
the
date
of
the
commercial
launch,
first-genera-
tion
antipsychotics
(FGAs,
‘old
antipsychotics’)
are
still
dif-
ferentiated
from
second-generation
antipsychotics
(SGAs,
‘new
antipsychotics’).
High-potency
FGAs
were
mainly
intro-
duced
in
the
1960s
and
1970s
and
act
predominately
as
dopamine-D2-receptor
antagonists.
This
D2-receptor
antag-
onism
is
responsible
for
the
neurological
side-effects
of
the
FGAs.
Clozapine
was
introduced
in
1972
and
was
the
first
SGA,
characterized
by
less
neurological
side-effects
than
the
known
FGAs.
From
the
early
1990s
till
today,
19
different
so-
called
SGAs
have
been
internationally
launched.
These
SGAs
are
characterized
by
a
heterogeneous
receptor
profile
(D2-
antagonism,
D4-antagonism,
5HT-agonism/antagonism
(on
different
subtypes),
mACh-Antagonims),
heterogeneous
effi-
cacy
and
a
heterogeneous
spectrum
of
side-effects.
Today,
this
classification
into
FGAs
and
SGAs
and
the
generalisation
of
receptor-binding
profile,
efficacy
and
side-
effects
within
each
group
must
be
considered
as
critical,
because
neither
SGAs
nor
FGAs
represent
a
homogenous
class
[
11
].
The
situation
is
further
complicated
by
the
important
fact
that
only
few
studies
compared
the
efficacy
of
the
FGAs
and
SGAs
in
the
treatment
of
first-episode
schizophrenia
patients
in
double-blinded
randomized
clinical
trials
with
a
satisfy-
ingly
large
sample
size.
From
1999
to
2011,
five
different
randomized
clinical
trials
with
a
large
sample
size
compared
FGAs
(haloperidol)
and
SGAs
(olanzapine
or
clozapine
or
risperidone)
and
these
studies
did
not
reveal
a
statistically
significant
difference
of
efficacy
[
12–16
].
In
2008,
the
first
head-to-head
comparison
between
FGAs
(haloperidol)
and
SGAs
(amisulpiride,
ziprasi-
done,
quetiapine,
olanzapine)
was
published
(EUFEST-Study
[
17
]),
showing
no
differences
concerning
efficacy
expressed
as
treatment
discontinuation.
These
findings
were
confirmed
in
a
recent
meta-analysis
including
150
double-blind
rando-
mized
clinical
trials
with
21,533
participants
revealing
no
efficacy
differences
between
FGAs
(haloperidol)
and
different
SGAs
[
11
].
Currently,
short-term
trials
could
not
detect
any
difference
of
efficacy
in
psychotic
symptom
reduction
between
FGAs
(especially
haloperidol)
and
SGAs,
whereas
some
few
long-term
trials
indicate
that
SGAs
might
be
super-
ior
to
FGAs
with
regard
to
relapse
prevention
[
10
].
However,
if
FGAs
and
SGAs
do
show
the
same
efficacy
in
the
treatment
of
positive
symptoms,
which
antipsychotic
class
should
be
used
for
the
treatment
of
first-episode
schizo-
phrenia?
Paradigms
are
changing
and
bit
by
bit
the
side-
effects
are
attached
greater
significance.
First-episode
schizo-
phrenia
patients
usually
are
young
patients
who
might
need
a
long-term
treatment
and
it
is
evident
that
side-effects
are
one
important
reason
for
treatment
discontinuation
and
non-
adherence
[
5,18
].
Side-effects
Antipsychotic
drugs
are
a
heterogeneous
drug
class
and
each
antipsychotic
has
its
individual
side-effect
profile.
A
wide
range
of
side-effects
has
been
described
elsewhere
[
5,10
],
but
in
summary
four
big
groups
of
side-effects
[
10,18
]
with
particular
importance
for
young
patients
are
emerging:
1.
Neurological
side
effects
(extrapyramidal
side-effects;
tard-
ive
dyskinesia,
acute
dystonia,
akathisia).
2.
Metabolic
side
effects
(weight
gain,
induction
of
diabetes,
hyperlipidemia).
3.
Prolactine
elevation
and
sexual
dysfunction.
4.
Cardiovascular
side-effects
(ECG-abnormalities,
QTc-pro-
longation,
tachycardia,
orthostatic
hypotension).
It
should
be
noticed
that
first-episode
patients
are
much
more
sensitive
to
the
various
side-effects
of
antipsychotic
drugs
than
multi-episode
schizophrenia
patients
[
5
].
Schizo-
phrenia
patients
in
general
have
an
illness-independent
risk
for
developing
a
metabolic
syndrome
[
19
]
and
untreated
first-
episode
patients
show
an
increased
amount
of
intra-abdom-
inal
fat
in
comparison
to
matched
healthy
controls
[
20
].
High-potency
FGAs
(like
haloperidol)
and
some
SGAs
(especially
risperidone/paliperidone,
but
other
SGAs,
too)
carry
the
risk
to
induce
neurological-side
effects,
whereupon
the
risk
for
such
side
effects
is
increased
following
a
treatment
with
FGA
in
first-episode
schizophrenia
patients
[
17
].
Both,
FGAs
and
SGAs
could
induce
weight-gain
and
a
metabolic
syndrome
[
21
],
but
certain
SGAs
(clozapine,
olanzapine,
que-
tiapine,
risperidone)
are
linked
to
the
highest
risk
of
this
side-
effect
[
5,10,17
].
Prolactine
elevation
is
associated
with
high-
potency
FGAs
and
some
SGAs
(especially
amisulpride
and
risperidone/paliperidone)
[
5,10,22
].
Last
but
not
least,
Drug
Discovery
Today:
Therapeutic
Strategies
|
Treatment
of
schizophrenia
Vol.
8,
No.
1–2
2011
32
www.drugdiscoverytoday.com
cardiovascular
side-effects
should
be
considered
when
using
antipsychotic
drugs.
All
antipsychotic
drugs
are
more
or
less
linked
to
cardiovascular
side
effects
[
5
].
Certain
SGAs
are
associated
with
a
significant
QTc
prolongation
(sertindole,
ziprasidone)
or
the
risk
of
inducing
a
myocarditis
(clozapine)
[
10,23
].
How
to
treat
psychotic
symptoms
in
first-episode
schizophrenia
patients?
Data
from
large
controlled
trials
comparing
the
efficacy
in
first-episode
schizophrenia
patients
are
still
lacking.
Because
of
practical
reasons
(easy
and
fast
inclusion
into
studies),
most
clinical
trials
have
been
conducted
in
chronically
ill
schizophrenia
patients.
Besides
the
development
of
new
therapeutic
agents,
the
established
antipsychotic
drugs
have
to
be
investigated
and
to
be
compared
in
additional
clinical
trials
with
a
large
number
of
first-episode
patients.
Today,
the
findings
from
multi-episode
patients
are
transferred
to
first-
episode
patients
and
the
findings
of
one
antipsychotic
drug
to
another
one.
Such
results
have
to
be
regarded
with
a
critical
eye.
Recent
publications
indicate
that
there
are
fundamental
neurobiological
differences
between
first-episode
and
multi-
episode
schizophrenia
patients
and
as
stated
before,
antipsy-
chotics
are
a
very
heterogeneous
group
and
therefore
difficult
to
compare.
First
of
all,
an
optimal
and
evidence
based
antipsychotic
treatment
of
first-episode
schizophrenia
should
follow
national
or
international
guidelines
[
5,10
].
Secondly,
each
patient
should
receive
an
individual
treatment
addressing
the
individual’s
risk
profile
for
side-effects,
the
individual’s
symp-
tomatology
and
the
individual’s
clinical
and
social
needs
[
11,24
].
Thirdly,
for
being
more
responsive
to
antipsychotic
treatment,
first-episode
schizophrenia
patients
have
an
increased
risk
to
develop
side-effects
[
10
].
Therefore,
they
should
be
treated
with
dosages
at
the
lower
end
of
the
standard
dose
range
[
10
].
Finally,
one
of
the
most
important
reasons
for
treatment
resistance
and
relapse
in
early
schizo-
phrenia
is
non-adherence
to
antipsychotic
medication
[
5
].
Therefore,
adherence
should
be
discussed
with
the
patient
(psychoeducation)
and
ensured
by
therapeutic
drug
monitor-
ing,
if
necessary.
Long-acting
formulations
of
antipsychotics
(FGAs
and
SGAs)
could
help
to
improve
adherence
and
to
reduce
the
relapse
rate
and
should
be
offered
to
patients
with
non-adherence.
Is
there
a
pharmacological
treatment
of
negative
symptoms?
Patients
with
a
first-episode
usually
present
positive
symp-
toms
at
their
first
contact
with
professional
healthcare.
Dur-
ing
the
disease
course,
negative
symptoms,
such
as
withdrawal
from
social
life,
apathy
and
anhedonia,
are
likely
to
occur.
A
couple
of
years
ago,
companies
claimed
an
improved
efficacy
of
SGAs
for
the
treatment
of
negative
symptoms
[
11
]
and
raised
hope
for
new
treatment
options.
However,
FGAs
and
SGAs
show
similar
efficacy
in
the
treat-
ment
of
negative
symptoms
by
both
only
slightly
improving
them
[
11,17,18
].
The
recently
published
recommendations
from
the
Schizophrenia
Patient
Outcomes
Research
Team
(PORT)
are
more
reserved
stating
an
‘insufficient
level
of
evidence
to
support
a
treatment
recommendation
for
any
pharmacological
treatment
of
negative
symptoms
in
schizo-
phrenia’
[
10
].
Implications
from
neuroscientific
research
Experimental
studies
indicate
pathophysiological
and
struc-
tural
changes
in
the
brain
of
schizophrenia
patients.
A
‘toxic’,
maybe
neurodegenerative
effect
of
psychosis
and
relapse
is
discussed
based
on
the
enhanced
symptom
severity,
the
reduced
neurocognitive
ability
and
the
reduced
drug
sensi-
tivity
in
multiple-episode
schizophrenia
patients
[
25
].
A
large
body
of
work
has
been
published
dealing
with
the
neurobiol-
ogy
of
the
disease
course
in
schizophrenia
and
we
would
like
to
introduce
three
recently
published
studies
to
the
reader.
One
longitudinal
MRI
study
(first
MRI
was
recorded
during
the
first-episode
with
a
consecutive
mean
follow-up
of
7
years)
revealed
that
antipsychotics
(no
matter
if
FGAs
or
SGAs)
have
a
significant
impact
on
brain
tissue
loss
over
time,
which
is
related
to
findings
from
animal
studies
in
macaque
monkeys
[
26
].
The
same
group
published
another
very
interesting
longitudinal
study
indicating
that
some
schizophrenia
patients
show
an
accelerated
and
progressive
decrement
in
brain
tissue
volume
compared
to
healthy
con-
trols
[
27
].
The
authors
investigated
first-episode
schizophre-
nia
patients
who
have
been
followed
up
to
18
years
and
found
the
greatest
volume
losses
during
the
early
stages
of
the
illness
[
27
].
Finally,
in
a
cross-sectional
proof-of-principle
study
we
showed
that
cortical
plasticity
is
affected
in
multiple-episode
schizophrenia
patients,
but
not
in
recent-onset
schizophre-
nia
patients
with
only
one
psychotic
episode
[
28
].
Summing
up,
there
is
neurobiological
evidence
for
a
dys-
functional
neuroplasticity
and
impaired
structural
integrity
during
the
disease
course
of
schizophrenia.
Today,
antipsy-
chotic
treatment
does
not
account
for
such
differences
between
first-episode
and
chronically
ill
schizophrenia
patients.
However,
new
antipsychotic
drugs
are
under
way
and
plasticity
modulating
therapies
might
provide
an
inno-
vative
treatment
option.
New
treatment
options
The
dopamine
hypothesis
of
schizophrenia
‘has
been
one
of
the
most
enduring
ideas
in
psychiatry’
[
29
],
but
many
other
neurotransmitters
and
neuromodulators
(glutamate,
acetyl-
choline,
endogenous
cannabinoid)
are
likely
to
be
involved
in
its
pathophysiology.
Therefore,
new
antipsychotic
drugs,
which
do
not
follow
the
pharmacological
principle
of
dopa-
mine/5-HT
2
antagonism
[
30
],
are
designed
to
target
other
Vol.
8,
No.
1–2
2011
Drug
Discovery
Today:
Therapeutic
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Treatment
of
schizophrenia
www.drugdiscoverytoday.com
33
receptor
systems
(especially
the
glutamate
and
acetylcholine
system).
A
detailed
overview
about
new
therapeutic
agents
is
published
elsewhere
[
31
].
Promising
novel
agents
are
LY-
404039,
a
metabotropic
glutamate
receptor
2/3
agonist
[
32
],
AVE1625,
a
cannabinoid-1-receptor
agonist
[
33
]
and
NS14492,
a
high-affinity
a
(7)nAChR-selective
partial
agonist
[
34
].
Furthermore,
phosphodiesterase
10A
(PDA10A)
inhibitors
are
discussed
to
provide
efficacy
in
the
treatment
of
schizo-
phrenia
[
35
].
Other
new
therapeutic
principles
are
the
mod-
ulation
of
5-HT(7)
receptors
[
36
]
or
of
dopamine
receptor
interacting
proteins,
like
NCS-1
[
37
].
These
agents
already
are
or
have
to
be
investigated
in
future
animal
studies/pre-clin-
ical-
and
clinical
trials.
In
schizophrenia
patients,
add
on
treatment
with
polyun-
saturated
fatty
acids
(e.g.
omega-3
or
omega-6
fatty
acids)
have
been
investigated
with
regard
to
their
efficacy
for
symp-
tom
reduction.
However,
an
important
meta-analysis
(Cochrane
review)
including
eight
different
studies
revealed
inconclusive
results
[
38
].
Therefore,
there
is
currently
not
enough
evidence
to
support
general
treatment
recommenda-
tions
with
polyunsaturated
fatty
acids.
Interestingly,
a
recently
published
double-blind,
placebo
controlled
randomized
clinical
trial
explored
the
efficacy
of
omega-3
fatty
acids
in
prodromal
patients.
This
study
found
that
omega-3
fatty
acids
reduce
the
risk
of
progression
to
psychotic
disorder
in
ultra-high-risk
prodromal
patients
[
39
].
In
conclusion,
omega-3
fatty
acids
may
be
a
promising
ther-
apeutic
option
in
future,
but
further
studies
need
to
confirm
these
preliminary
findings.
In
chronically
ill
patients,
treatment
approaches
to
enhance
neuroplasticity
were
shown
to
be
promising
in
small
proof-of
principle
studies
and
clinical
trials.
We
performed
a
sham-controlled
clinical
trial
to
investigate
the
influence
of
exercise
on
cognition
and
brain
volume
in
chronic
schizo-
phrenia.
Exercise
resulted
in
a
significant
increase
of
hippo-
campal
volume
(mean:
15%),
in
an
increase
of
hippocampal
n-acetyl-aspartate
(a
marker
for
neuronal
integrity)
and
in
an
improved
performance
in
verbal
and
spatial
working
memory
[
40
].
Weekly
intravenous
recombinant
erythropoietin
(EPO)
halts
the
progressive
cortical
atrophy
in
chronic
schizophre-
nia
and
improves
attention
and
memory
functions
[
41
].
Molecular
and
cell
studies
support
these
findings,
because
EPO
is
known
to
stimulate
axonal
sprouting,
synaptogenesis
and
to
modulate
synaptic
plasticity
[
42
].
Finally,
low
frequency
transcranial
magnetic
stimulation
(TMS)
is
proved
to
be
effective
and
is
therefore
recommended
for
the
treatment
of
refractory
auditory
hallucinations
[
10
].
In
summary,
modulation
of
neuroplasticity
might
be
pro-
mising
for
the
future
treatment
of
schizophrenia.
Especially,
transcranial
non-invasive
brain
stimulation
techniques,
like
TMS
or
transcranial
direct
current
stimulation
(tDCS),
have
to
be
further
investigated
and
tested
for
possible
application
in
schizophrenia.
However,
all
new
antipsychotic
drugs
and
treatment
strategies
have
to
be
proven
in
first-episode
patients,
because
till
today
all
studies
have
been
conducted
in
chronically
ill
patients.
Conclusions
Schizophrenia
is
a
disorder
with
a
heterogeneous
symptoma-
tology
presenting
a
wide
array
of
symptoms:
positive
symp-
toms,
negative
symptoms,
cognitive
impairments,
affective
symptoms,
suicidality
and
many
more.
There
are
clinical
and
neurobiological
differences
between
the
early
course,
the
first-episode
and
the
chronic
illness.
Therefore,
hoping
for
one
magic
bullet
for
all
disease
stages
and
all
symptom
complexes
is
highly
unrealistic.
In
the
future,
new
treatment
strategies
apart
from
dopamine
antagonists
and
5HT-receptor
modulating
drugs
are
needed.
Today,
a
modern
and
evidence-
based
treatment
of
first-episode
schizophrenia
should
follow
the
recommendations
of
national
and
international
guide-
lines
with
particular
emphasis
on
the
side-effects
of
antipsy-
chotics.
Furthermore,
it
should
be
remembered
that
the
currently
available
antipsychotics
are
powerful
drugs
in
the
treatment
of
positive
symptoms
and
relapse
prevention,
but
have
only
little
effects
on
negative
and
affective
symptoms.
First-episode
schizophrenia
patients
display
prominent
differences
in
symptomatology,
response
to
antipsychotic
treatment,
sensitivity
to
drug
side-effects
and
in
the
under-
lying
neurobiology.
Therefore,
the
knowledge
transfer
from
the
findings
in
chronically
ill
patients
to
first-episode
patients
should
be
regarded
with
caution.
More
baseline
studies
and
longitudinal
follow-up
studies
are
needed
to
extend
the
knowledge
about
the
neurobiology
and
the
disease
course
of
schizophrenia
patients.
Larger
well-designed
double-
blinded
randomized
trials
with
head-to-head
comparisons
of
the
available
antipsychotic
drugs
in
first-episode
are
also
needed
to
improve
the
treatment
and
to
allow
more
evi-
dence-based
recommendations.
Antipsychotics
have
revolutionised
the
treatment
of
schi-
zophrenia
after
their
introduction
in
the
1950s.
They
are
the
greatest
achievement
in
psychiatry
and
they
improved
the
treatment,
the
quality
of
life
and
the
disease
prognosis
of
schizophrenia
patients.
Now
it
is
time
to
take
the
next
step
towards
further
therapeutic
improvements
and
we
have
a
legitimate
hope
that
in
future
there
will
be
new
treatment
options
available.
Conflicts
of
interest
A.
Hasan
was
invited
to
scientific
congresses
by
Astra
Zeneca
and
Lundbeck.
T.
Wobrock
was
a
member
of
a
speaker
bureau
for
Alpine
Biomed,
AstraZeneca,
Eli
Lilly,
Essex,
Janssen
Cilag;
has
accepted
paid
speaking
engagements
in
industry-spon-
sored
symposia
from
Alpine
Biomed,
AstraZeneca,
Bristol
Myers
Squibb,
Eli
Lilly,
Janssen
Cilag,
Lundbeck,
Sanofi-Aventis
Drug
Discovery
Today:
Therapeutic
Strategies
|
Treatment
of
schizophrenia
Vol.
8,
No.
1–2
2011
34
www.drugdiscoverytoday.com
and
Pfizer,
and
travel
or
hospitality
not
related
to
a
speaking
engagement
from
AstraZeneca,
Bristol-Myers-Squibb,
Eli
Lilly,
Janssen
Cilag,
and
Sanofi-Synthelabo;
and
has
received
a
research
grant
from
AstraZeneca.
D.
Reich-Erkelenz
reports
no
conflicts
of
interest.
P.
Falkai
was
honorary
speaker
for
Janssen-Cilag,
Astra-Zeneca,
Lilly,
BMS,
Lundbeck,
Pfizer,
Bayer
Vital,
SKB,
Wyeth,
Essex
and
during
the
last
two
years,
but
not
presently,
he
was
member
of
the
advisory
boards
of
Janssen-
Cilag,
Astra-Zeneca,
Lilly
and
Lundbeck.
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Drug
Discovery
Today:
Therapeutic
Strategies
|
Treatment
of
schizophrenia
www.drugdiscoverytoday.com
35