Early intervention in psychosis: Concepts, evidence and future directions

Article (PDF Available)inWorld psychiatry: official journal of the World Psychiatric Association (WPA) 7(3):148-56 · November 2008with437 Reads
DOI: 10.1002/j.2051-5545.2008.tb00182.x · Source: PubMed
  • 52.99 · Orygen:The National Centre of Excellence in Youth Mental Health and University of Melbourne
  • 38.01 · University of Melbourne
  • 48.21 · The University of Manchester
The rise of the early intervention paradigm in psychotic disorders represents a maturing of the therapeutic approach in psychiatry, as it embraces practical preventive strategies which are firmly established in mainstream health care. Early intervention means better access and systematic early delivery of existing and incremental improvements in knowledge rather than necessarily requiring dramatic and elusive breakthroughs. A clinical staging model has proven useful and may have wider utility in psychiatry. The earliest clinical stages of psychotic disorder are non-specific and multidimensional and overlap phenotypically with the initial stages of other disorders. This implies that treatment should proceed in a stepwise fashion depending upon safety, response and progression. Withholding treatment until severe and less reversible symptomatic and functional impairment have become entrenched represents a failure of care. While early intervention in psychosis has developed strongly in recent years, many countries have made no progress at all, and others have achieved only sparse coverage. The reform process has been substantially evidence-based, arguably more so than other system reforms in mental health. However, while evidence is necessary, it is insufficient. It is also a by-product as well as a catalyst of reform. In early psychosis, we have also seen the evidence-based paradigm misused to frustrate overdue reform. Mental disorders are the chronic diseases of the young, with their onset and maximum impact in late adolescence and early adult life. A broader focus for early intervention would solve many of the second order issues raised by the early psychosis reform process, such as diagnostic uncertainty despite a clear-cut need for care, stigma and engagement, and should be more effective in mobilizing community support. Early intervention represents a vital and challenging project for early adopters in global psychiatry to consider.

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World Psychiatry 7:3 - October 2008
Psychotic disorders and particularly
schizophrenia are serious and some-
times fatal illnesses which typically
emerge during the sensitive developmen-
tal period of adolescence and emerging
adulthood (1). For over a century, a cor-
rosive blend of pessimism, stigma and
neglect have confined therapeutic ef-
forts to delayed and inconsistent pallia-
tive care. Much of this can be attributed
to the conceptual error underpinning
the concept of schizophrenia, namely
that a true disorder could be validly de-
fined by its (poor) outcome. This error
was, in turn, a legacy of the 19th century
degeneration theory, which has been al-
lowed to influence the field well beyond
its use-by date (2). Although Kraepelin
himself and some of his contemporaries
ultimately recognized the fallacy, his di-
chotomy (between dementia praecox
and manic depressive insanity) has with-
stood several challenges and has been
strongly reinforced with the advent of
operational diagnostic systems. This has
not only hampered neurobiological re-
search, but has caused widespread iat-
rogenic harm and inhibited early diag-
nosis because of an exaggerated fear of
Early intervention in psychosis: concepts, evidence
and future directions
FORUM: EaRly INTERVENTION IN psychOsIs: clINIcal aNd EThIcal challENgEs
Pa t r i c k D. McGo r r y 1, Eó i n ki l l a c k E y 1,2, al i s o n yu n G 1
1ORYGEN Research Centre and Department of Psychiatry, and 2 Department of Psychology, University of Melbourne, 35 Poplar Rd., Parkville, Victoria, Australia
The rise of the early intervention paradigm in psychotic disorders represents a maturing of the therapeutic approach in psychiatry, as it
embraces practical preventive strategies which are firmly established in mainstream health care. Early intervention means better access
and systematic early delivery of existing and incremental improvements in knowledge rather than necessarily requiring dramatic and
elusive breakthroughs. A clinical staging model has proven useful and may have wider utility in psychiatry. The earliest clinical stages
of psychotic disorder are non-specific and multidimensional and overlap phenotypically with the initial stages of other disorders. This
implies that treatment should proceed in a stepwise fashion depending upon safety, response and progression. Withholding treatment
until severe and less reversible symptomatic and functional impairment have become entrenched represents a failure of care. While early
intervention in psychosis has developed strongly in recent years, many countries have made no progress at all, and others have achieved
only sparse coverage. The reform process has been substantially evidence-based, arguably more so than other system reforms in mental
health. However, while evidence is necessary, it is insufficient. It is also a by-product as well as a catalyst of reform. In early psychosis,
we have also seen the evidence-based paradigm misused to frustrate overdue reform. Mental disorders are the chronic diseases of the
young, with their onset and maximum impact in late adolescence and early adult life. A broader focus for early intervention would solve
many of the second order issues raised by the early psychosis reform process, such as diagnostic uncertainty despite a clear-cut need for
care, stigma and engagement, and should be more effective in mobilizing community support. Early intervention represents a vital and
challenging project for early adopters in global psychiatry to consider.
Key words: Early intervention, psychosis, staging, health care reform, youth mental health
(World Psychiatry 2008;7:148-156)
the expected outcome.
Until recently, apart from transient
and illusory optimism generated by the
mental hygiene movement in the 1920s,
early intervention for psychotic disor-
ders has been the furthest thing from
the minds of clinicians and research-
ers. Ironically, however, since the early
1990s, this hitherto barren landscape
has seen the growth of an increasingly
rich harvest of evidence, and wide-
spread national and international efforts
for reform in services and treatment ap-
proaches, setting the scene for more
serious efforts in early intervention in
other mental disorders (3-5).
Building on seminal research on first
episode psychosis from the 1980s (6-8),
frontline early psychosis clinical ser-
vices were established, first in Melbourne
(9) and soon after in many key locations
in the UK, Europe, North America and
Asia (10). There are now hundreds of
early intervention programs worldwide,
of varying intensity and duration, which
focus on the special needs of young peo-
ple and their families. International clin-
ical practice guidelines and a consensus
statement have been published (11) and
clinical practice guidelines for the treat-
ment of schizophrenia now typically
have a major section on early psychosis
(12,13). The International Early Psycho-
sis Association (www.iepa.org.au), an
international organization which seeks
to improve knowledge, clinical care and
service reform in early psychosis, has
been in existence for over ten years, led
by a highly collegial leadership group of
clinicians and researchers. This associa-
tion has over 3000 members from over
60 different countries, and by 2008 will
have held six international conferences,
stimulating and capturing a large vol-
ume of research and experience.
In recent months, responding to the
widespread international momentum,
the US National Institute of Mental
Health has announced a large new
funding initiative to study and promote
the development of better services for
patients with first episode psychosis
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World Psychiatry 7:3 - October 2008
Shift in thinking: pessimism
to optimism
The advent of preventive thinking has
required a shift in the way schizophre-
nia and other psychotic disorders are
viewed. Rather than seeing them as hav-
ing inevitably poor prognoses with de-
terioration in social and functional out-
come as the norm, more recent thinking
backed up by evidence from large inter-
national studies (14-25) views the course
of these disorders as much more fluid
and malleable.
Examination of risk factors which
can influence outcome has revealed that
many of these may be reversible. For
example, disruption of peer and family
networks and vocational drop-out com-
monly occur around and even before
the onset of a first psychotic episode.
Attention to these areas as part of treat-
ment has the potential to limit or repair
the damage.
Comorbid depression, substance use,
personality dysfunction and post-trau-
matic stress disorder (PTSD) are all fac-
tors which may influence outcome in
a person with first episode psychosis.
Again, early and vigorous management
of these problems can result in better
outcomes (26).
What is early intervention?
Early intervention is a potentially
confusing term. Because there is no
aetiopathological basis for diagnosing
psychotic disorders, they can only be
diagnosed by symptoms or combina-
tions of symptoms. In addition, we have
no known malleable causal risk factors
which predict onset of psychotic disor-
der with any specificity. Thus, it seems
that primary prevention is currently out
of our reach. Early intervention, there-
fore, means early secondary prevention.
In keeping with the clinical staging
model (27) articulated below, early in-
tervention in psychosis can be defined
as comprising three foci or stages: ultra-
high risk, first episode, and the recovery
or critical period. The principal reason
for making such distinctions relates to
the underlying risk of chronicity, and
specifically the timing and duration of
prescription of antipsychotic medica-
tion, since psychosocial interventions
are needed at all stages, though these
interventions too vary by stage.
What is the target for early intervention:
schizophrenia or psychosis?
Clinicians and researchers have de-
bated whether to focus on the preven-
tive target of schizophrenia or of psy-
chotic disorders more broadly. There are
several reasons for stepping out of the
current diagnostic silos and preferring a
relatively broad target.
As described above, schizophrenia
is conceived and defined in part as an
outcome as much as a diagnosis. While
it is very stable once applied (28-31), it
is intrinsically difficult to apply until the
patient has been ill for a prolonged peri-
od of time. Within a sample of ultra-high
risk cases (already defined in order to
preferentially predict transition to non-
affective psychosis), only 75% of those
who go on to develop a first episode
psychosis will progress to a schizophre-
nia diagnosis (32). So, the false positive
rate is higher for schizophrenia than for
first episode psychosis. Even within a
first episode psychosis sample, only 30-
40% will meet criteria for schizophrenia,
and this percentage will increase over
time with additional diagnostic flux.
Thus, some cases of first episode psy-
chosis which do not meet criteria for
schizophrenia can be seen as being at
risk for this in the future (33). Schizo-
phrenia, therefore, is to some extent a
more distal target than psychosis, which
is a better and broader initial waystation
for critical treatment decisions. An even
earlier and broader point for interven-
tion is the ultra-high risk clinical stage,
where there is a need for care prior to
the positive psychotic symptoms having
become severe and sustained.
In addition, due to fear and stigma
derived from the notion of intrinsic poor
prognosis, clinicians are reluctant to
use the label “schizophrenia” early on
anyway, justifiably concerned about iat-
rogenic effects on hope and the poten-
tial for recovery (34). This has led some
countries, such as Japan, to change their
diagnostic terminology and eschew the
word “schizophrenia” (35). Our preferred
alternative is to retain it for the time be-
ing, as one subtype of psychotic disorder
outcome, admittedly a major one, among
a small range of distal targets.
Psychosis itself is a variable syndrome,
defined by the presence of positive psy-
chotic symptoms, especially delusions
and hallucinations, and typically features
one or many comorbidities, including
negative symptoms, mood syndromes,
personality disorders, substance use
disorders, medical diseases and PTSD.
The relative prominence of the positive
symptoms and comorbidities varies, and
this leads to a more heterogeneous group
of patients. As a consequence of this, a
broader range of clinical skills will be re-
quired in early psychosis programs than
in narrower schizophrenia programs.
Some have argued that the schizo-
phrenia focus allows the other psychot-
ic disorders, especially psychotic mood
disorders and psychoses associated with
certain personality disorders and PTSD,
to be treated in more appropriate set-
tings. However, provided there is a flexi-
ble attitude and a broad range of clinical
expertise available, both groups of pa-
tients benefit more from this broad, ear-
ly, and inclusive focus on the spectrum
of psychosis. It provides a good balance
between specialization and addressing
common needs, and also facilitates both
clinical and aetiological research, which
increasingly needs to transcend tradi-
tional diagnostic barriers.
Many of the problems of categori-
cal diagnosis flow from a telescoping of
syndromes and stages of illness which
conceals and distorts the natural ebb
and flow of illness, remission and pro-
gression. In addition to augmenting
categorical approaches with symptom
dimensions, consideration needs to be
given to the dimensions of time, sever-
ity, persistence and recurrence.
The notion of staging can be borrowed
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World Psychiatry 7:3 - October 2008
and adapted from mainstream medicine
to assist us here. A clinical staging model
provides a heuristic framework allowing
the development and evaluation of broad
and specific interventions as well as
the study of the variables and processes
underlying the evolution of psychiatric
disorder (27,36).
What is clinical staging?
Clinical staging is simply a more re-
fined form of diagnosis (37,38). Its value
is recognized in the treatment of malig-
nancies, where quality of life and surviv-
al rely on the earliest possible delivery
of effective interventions. However, it
also has applicability in a diverse range
of diseases. Clinical staging differs from
conventional diagnostic practice in that
it defines the extent of progression of
disease at a particular point in time, and
where a person lies currently along the
continuum of the course of illness (36).
The differentiation of early and milder
clinical phenomena from those that ac-
company illness extension, progression
and chronicity lies at the heart of the
concept. It enables the clinician to select
treatments relevant to earlier stages, and
assumes that such interventions will be
both more effective and less harmful than
treatments delivered later in the course.
While staging links treatment selec-
tion and prediction, its role in the former
is more crucial than in the latter, par-
ticularly since early successful treatment
may change the prognosis and thus pre-
vent progression to subsequent stages.
In addition to guiding treatment selec-
tion, a staging framework, which moves
beyond the current diagnostic silos to
encompass a broader range of clinical
phenotypes, and which at the same time
introduces subtypes along a longitudinal
dimension, has the potential to organize
endophenotypic data in a more coherent
and mutually validating fashion (36).
How do we define the stages
of a disorder?
In other medical conditions, clinical
stages are defined by the degree of ex-
tent, progression and biological impact
of illness in the patient, which in turn
must correlate with prognosis. This ap-
proach usually depends upon a capacity
to define pathologically as well as clini-
cally the limits or extent of the disease
In clinical psychiatry, this could in-
volve not only a cross-sectional clinical
definition, but a wider biopsychoso-
cial definition of extent or progression.
Therefore, in addition to the severity,
persistence and recurrence of symptoms,
biological changes (e.g., hippocampal
volume loss), and the social impact of
the disorder (e.g., the collateral dam-
age affecting social relationships and
employment), could also be drawn into
the definition. Ultimately, something ap-
proaching a clinicopathological model
could emerge.
What are the potential benefits
of staging?
On the clinical side, defining dis-
crete stages according to progression of
disease creates a prevention-oriented
framework for the evaluation of inter-
ventions. The key positive health out-
comes are prevention of progression
to more advanced stages, or regression
to an earlier stage. This requires an ac-
curate understanding of those broad
social, biological and personal risk and
protective factors which influence pro-
gression from one stage to the next.
Furthermore, we need to know the
relative potency of these risk factors and
which of them may be responsive to cur-
rent interventions. While some factors
may operate across several or all stage
transitions, others may be stage-specific,
for example substance abuse or stress
may be especially harmful in trigger-
ing onset of the first episode of illness,
yet be less toxic subsequently (or vice
versa). Gene-environment interactions
almost certainly underpin and mediate
these transitions, where environmental
variables − such as substance abuse,
psychosocial stressors, cognitive style,
medication adherence and social iso-
lation may interact with genetic and
other biological risk factors (39-41).
From an aetiological perspective, over
a century of research with traditional di-
agnostic categories of psychosis and se-
vere mood disorders has failed to relate
these flawed concepts to any discrete
pathophysiology (42,43). A clinical stag-
ing model, which allows the relationship
of biological markers to stage of illness
to be mapped, may help to validate the
boundaries of current or newly defined
clinical entities, distinguish core biologi-
cal processes from epiphenomena and
sequelae, and enable existing knowl-
edge to be better represented and under-
Stage 1: Ultra-high risk
In psychotic disorders, an early
prepsychotic stage is known to exist, one
in which much of the collateral psycho-
social damage is known to occur (44).
This earliest stage could, in retrospect, be
termed the “prodrome”, i.e., the precur-
sor of the psychotic stage. However, since
we can only apply the term “prodrome”
with certainty if the definitive psychotic
stage does indeed develop, terms such as
the “ultra-high risk” (34) or “clinical high
risk” (45) stage have been developed to
indicate that psychosis is not inevitable
and that false positive cases also occur.
This symptomatic yet prepsychotic stage
is the earliest point at which preventive
interventions for psychosis can concur-
rently be conceived (46).
The challenge in detecting such a
stage prospectively is firstly to define the
clinical frontier for earliest intervention
and “need for care” which represents
the boundary between normal human
experience and pathology. Secondly, a
set of clinical and other predictors need
to be defined which identify a subgroup
at imminent risk for psychotic disorder.
This is a complex task and the key issues
involved have been covered in many
recent publications (47-55). Earlier
writers (56) aspired to the diagnosis of
schizophrenia in the prodromal phase.
German psychopathologists in the mid
20th century emphasized subtle changes
in experience and behaviour, though
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their complexity meant that they had
little impact on Anglophone psychiatry
initially. A practical operational defini-
tion of a prepsychotic “at risk” or “ultra-
high risk” mental state, which could be
shown to confer a substantially high risk
of fully fledged psychosis within a 12
month period, was then developed and
tested in the early 1990s (57). This has
captured the attention of the field and
has been the focus of much subsequent
research, focusing on prediction, treat-
ment and neurobiological aspects.
These criteria do indeed predict an
“ultra-high risk” group for early transi-
tion to psychosis (32), leading to a rela-
tive risk of 40% compared to the incident
rate of psychotic disorders in the general
population (58). However, there is still a
significant false positive rate of 60-80%,
though they typically are or turn out to
be true positives for other disorders, no-
tably depression and anxiety disorders.
While the predictive power for psychosis
can be substantially sharpened post-hoc
by the use of key variables such as ge-
netic risk, depression, functional impair-
ment and substance use (58,59), this is
of limited utility due to the “prevention
paradox”. This means that increasing
the positive predictive value reduces the
number and percentage of cases that can
benefit. So, if the sample is narrowed,
one is on firmer ground, but most cases
who do go on to develop the disorder
are missed due to the narrower focus
(51). We know already that most cases
of first episode psychosis are already
missed by prodrome clinics.
There have been a series of clinical tri-
als of relatively small sample size exam-
ining both antipsychotics and/or cog-
nitive therapy as preventive treatment
strategies for ultra-high risk patients (60-
62). These trials suggest that cognitive
therapy and antipsychotics may prevent
or at least delay the onset of psychotic
disorder and reduce symptomatology. A
second generation of single site clinical
trials has recently been completed, with
interesting results for a range of psycho-
social and biological therapies, includ-
ing cognitive therapy (62), lithium (63),
omega-3 fatty acids (64), and atypical
antipsychotics (60).
However, treating young people in
the putative prodromal phase does cause
some understandable concern that pa-
tients might be exposed to unnecessary
and potentially harmful treatments. This
has created controversy in the US in par-
ticular around this type of research. This
in turn has led to so-called “naturalistic
designs” (58,65) being preferred above
the traditional randomized designs. Par-
adoxically, the ethical considerations
that drove this thinking have allowed
the same treatments that could not be
researched under rigorous conditions
of informed consent within a random-
ized controlled trial to be used off label
in a widespread and uncontrolled fash-
ion in these naturalistic studies. Hence
the term “naturalistic” becomes a mis-
nomer, since the natural course may be
profoundly influenced by uncontrolled
treatment. These “naturalistic” stud-
ies reveal that extensive non-evidence-
based use of antipsychotic medications
seems to be common in clinical settings
in the US, ironically side by side with
long delayed and inadequate treatment
of first episode and established psychot-
ic disorders (66).
Next steps
Clinical trial data is crucial to deter-
mining the risks and benefits of various
forms of treatment in a new clinical fo-
cus and creating solid foundations for
an evidence-based approach. This is the
best antidote to fears on widespread and
potentially harmful and unnecessary
use of antipsychotic medications in par-
ticular. The “prodromal” or ultra-high
risk field remains in clinical equipoise,
since we do not yet know which treat-
ments will be most helpful and accept-
able to patients, and crucially in which
sequence or combination.
Prospective or naturalistic data can
best be collected in the most sound and
interpretable fashion in the context of
a large well-funded multicentre clinical
trial, with an “effectiveness” rather than
efficacy design and a minimal interven-
tion arm, to which non-consenters to
randomisation can be assigned.
We can readily accept that anti-
psychotics and indeed antidepressants
(67) and neuroprotective agents such as
omega-3 fatty acids and lithium are legit-
imate therapies to be further researched,
but their use in research should be pro-
tocolized within rigorous study designs.
In the meantime, the international clini-
cal practice guidelines on early psycho-
sis (11), which advocate a conservative
approach to the use of antipsychotic
medications and more liberal use of
psychosocial interventions, should be
followed. This rather conservative ap-
proach to treatment of ultra-high risk
individuals is even more imperative, as
recently it has been discovered that the
rates of early transition to first episode
psychosis have been falling in the more
established prodromal centres (52), with
a much higher rate of so-called “false
positives” being accepted into these
services. This may be due to sampling
variation, earlier detection of ultra-high
risk cases, or improved efficacy of inter-
ventions provided (52).
This reduction in transition rate and
uncertainty over treatment in the ultra-
high risk group has led to valid concerns
about identification of and intervention
with these individuals. Yet help-seek-
ing patients defined by the ultra-high
risk criteria for first episode psychosis
are at risk not only for schizophrenia or
psychosis but for other adverse mental
health outcomes (68). We may need to
define an even broader pluripotential
initial clinical stage with a range of pos-
sible exit or target syndromes. Conse-
quently, we have broadened our own
clinical and research strategy (69), cross-
sectionally with the development of a
broader and more accessible system of
clinical care for those in the peak age of
risk for all types of mental disorders (70-
72), and longitudinally with the creation
of a clinical staging model for psychotic,
mood and anxiety disorders (27).
This enables a serial enriching strat-
egy to unfold to ensure that the declin-
ing transition rates in ultra-high risk
samples (52) and the consequently
high false positive rate can be handled
in future clinical trials, and that other
exit syndromes and indeed remission
and resolution can be included. These
strategies help us to move beyond some
of the obstacles to early diagnosis and
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World Psychiatry 7:3 - October 2008
intervention: namely the “false positive”
issue, potential problems with stigma,
the challenge of comorbidity, and lack
of predictive specificity. As we move fur-
ther down this road, the problems with
our historically determined classifica-
tion systems loom larger and the need
to loosen the shackles becomes more
Stage 2: Early detection and treatment
of first episode psychosis
The second stage involves a therapeu-
tic focus on the period after the onset of
fully-fledged psychosis (often known
as “first episode psychosis”). This is di-
vided into the period before psychosis
is detected and the period after detec-
tion. Unfortunately, the undetected or
untreated phase can be prolonged, even
in developed countries (73). Of course,
even when psychosis is detected, the
initiation of effective treatment may still
be delayed. The goal is to minimize this
duration of untreated psychosis (DUP).
Post-detection, the intervention goals
are engagement and initiation of phar-
macological and psychosocial treat-
ments. Intensive interventions aimed at
maximal symptomatic and functional
recovery and the prevention of relapse
are ideally delivered during the early
weeks and months of treatment.
The controversy surrounding the im-
portance of DUP and treatment delay
in first episode psychosis seems to have
been largely resolved following the pub-
lication of some key systematic reviews
(74,75) and recent influential longitu-
dinal research. These studies have now
established that longer DUP is both a
marker and independent risk factor for
poor outcome. The Early Treatment and
Identification of Psychosis (TIPS) study
in Scandinavia has shown, through the
best possible design, that reducing DUP
leads to early benefits in reducing sui-
cidal risk and severity of illness at ini-
tial treatment and sustained benefits in
terms of negative symptoms and social
functioning (18-21). The relationship
between DUP and outcome is robust,
being sustained over many years of fol-
low-up (76,77). However, these studies
do show that, though being a malleable
risk factor, DUP accounts for a relatively
modest amount of outcome variance,
underlining the importance of treatment
access and quality during the early years
of illness.
There is an extensive literature at-
testing to the benefits of comprehen-
sive care of the first psychotic episode.
This is summarised in the International
Clinical Practice Guidelines for Early
Psychosis (11), published in 2005. Since
2005, the growth in research in this area
has continued. This has led to the emer-
gence of the following findings.
The large multicentre European First
Episode Schizophrenia Trial (EUFEST)
has shown that in the treatment of first
episode schizophreniform and schizo-
phrenic disorders, atypical or second-
generation antipsychotics have some
clear-cut advantages (78). While most
patients responded surprisingly well to
both typical and atypical medications,
with no significant efficacy differences,
discontinuation rates and tolerability
were clearly superior for atypical agents.
This was true even when contrasted with
very low-dose haloperidol. While the
authors’ conclusions and recommen-
dations were conservative, highlighting
the equivalent efficacy of the two classes
of drug, the EUFEST findings contrast
markedly with those of the Clinical An-
tipsychotic Trials of Intervention Effec-
tiveness (CATIE) study (79) in chronic
schizophrenia, where no dramatic ad-
vantages were found for atypicals using
similar outcome measures. The EUFEST
data support the recommendations of the
International Clinical Practice Guide-
lines in Early Psychosis (11), which favor
the use of atypicals as first line therapy,
because of better tolerability (a crucial is-
sue in drug-naïve first episode patients)
and reduced risk for tardive dyskinesia.
However, some atypicals have a particu-
larly high risk of weight gain and meta-
bolic problems, and these risks need to
be carefully managed and prevented
wherever possible. A recent paper (80),
however, suggests that weight gain is a
problem in the first year of therapy for
first episode patients on both typicals
and atypicals, with the key difference be-
ing the rate at which it develops.
Psychosocial treatments in early psy-
chosis have been extensively studied,
and there are positive findings pointing
to the value of cognitive therapies in ac-
celerating and maximizing symptomatic
and functional recovery (81,82). Increas-
ingly there has been attention to the
fact that medications, while assisting in
symptomatic recovery, do not, by them-
selves, contribute to a return to function-
ing. This has led to an increased focus on
the need to enhance social recovery (68)
especially educational and vocational as-
pects (83-85), through the combination
of effective psychosocial interventions
with well-managed medication. There
is also an increasing focus on targeted
cognitive remediation (86) to limit the
degree of cognitive decline that is often
found as illness progresses.
Next steps
Initial scepticism regarding DUP has
slowly melted in the face of evidence but
also the logic of early diagnosis. If we
believe we have effective interventions
in psychosis, it is perverse to argue that
delayed treatment is acceptable. Scep-
tics find themselves being asked how
long a delay is acceptable: 2 months? 6
months? 2 years? In reducing the DUP
the two key components of intervention
are community awareness and mobile
detection services. Both are important,
as the data from TIPS (87) and other
studies (88) have shown. When both are
in place, it is possible to achieve very low
levels of DUP (a median of a few weeks
only). These strategies also result in a less
risky and traumatic mode of entry into
care and enable patients to be engaged
without a surge of positive symptoms
or disturbed behaviour being required
to force entry into poorly accessible or
highly defended service systems. They
should be available in all developed
communities and a standard feature of
all mental health systems.
In terms of the specific elements of
first episode psychosis intervention, a
number of trials have shown that atypical
antipsychotics in low dose are superior
for first episode patients where tolerabil-
ity and safety are at a premium, though
148-156.indd 152 29-09-2008 8:39:05
World Psychiatry 7:3 - October 2008
some may be ruled out on exactly these
grounds in many patients. The recent
EUFEST study is especially compelling
(78). The place of new injectables and
clozapine needs to be clarified, as well as
that of adjunctive neuroprotective agents
such as omega-3 fatty acids, lithium and
N-acetyl cysteine. Cognitive behavioural
therapy and vocational rehabilitation
(89) are the key psychosocial interven-
tions in early psychosis and need to be
much more intensively and widely de-
ployed. Assertive community treatment
for the subset of poorly engaged patients
is vital (11). Family interventions are also
an essential element of care, even though
the formal evidence is not yet fully avail-
able (90).
Stage 3: The critical period of the first
5 years after diagnosis
This third stage involves the criti-
cal early years beyond the first episode,
which can be viewed as the critical pe-
riod (91). Treatment goals in this phase
are the management of effective medi-
cation and the use of effective psycho-
social interventions to minimize the
development of disability and maximize
functioning. Proof of concept is now
established for these strategies (14,15).
However, there remains a large gap in
most communities between what works
and what is available, even in high in-
come countries and certainly in the low
and middle income countries (92).
Beyond the first episode, we know
that the first 2-5 years post-diagnosis are
crucial in setting the parameters for lon-
ger term recovery and outcome. This is
the period of maximum risk for disen-
gagement, relapse and suicide, as well as
coinciding with the major developmen-
tal challenges of forming a stable identi-
ty, peer network, vocational training and
intimate relationships. It makes sense
that a stream of care specially focused
on young people and on this stage of ill-
ness is required to maximize the chances
of engagement, continuity of care, ap-
propriate lifestyle changes, adherence
to treatment, family support and voca-
tional recovery and progress. Indeed, the
available evidence from naturalistic and
randomized studies strongly supports
the value of specialized early psychosis
programs in improving outcome in the
short term (89,93). If these programs
are only provided for 1-2 years, there is
also evidence that some of the gains are
eroded, suggesting that, for a substantial
subset at least, specialized early psycho-
sis care needs to be provided for a longer
period, probably up to 5 years in many
cases (77,94,95).
Next steps
The best available evidence indicates
that streamed care provides superior
outcomes in the short to medium term
compared to generic care (16,17). While
this may be insufficient to meet the
most stringent Cochrane criteria, such
evidence, combined with face validity
and obvious poorly met need, has been
sufficient to convince mental health
policy makers and service providers
in hundreds of locations worldwide to
adopt, adapt and implement this model.
The randomized controlled trials so far
have only tested partial versions of this
streaming, with a specialized assertive
community treatment model being the
main feature evaluated. Even so the re-
sults are positive for the first 2 years of
care. It seems likely that, for a significant
subset at least, if these gains are to be
maintained, the streamed early psycho-
sis model must be continued for longer,
perhaps up to 5 years (89). At this point,
persisting illness and disability may be
present in a much smaller percentage of
people, whose needs may subsequently
be well met by more traditional mental
health services for older adults. This may
be a much better point to transfer care.
The pace of reform is typically slow
in health care. While early intervention
in psychosis has made great progress in
recent years, dissemination remains in
many ways frustratingly slow. Many de-
veloped and most developing countries
have made no progress at all, and even
those countries which have made sig-
nificant investments have only achieved
partial coverage. We have previously
commented on this inertia and some of
the reasons for it (92,96).
Evidence-based health policy (97)
can be seen as a blend of evidence-based
health care and public policy analysis,
in which evidence is only one of a range
of influential variables. Pure evidence-
based health policy derives from a tech-
nical perspective and regards the task as
identifying and overcoming barriers to
smooth flow of best available evidence
into practice. This has been characterised
as “naïve rationalism” (98), since cultur-
al and political values and the dynamics
of change and reform are other key in-
fluences on policy making. Evidence is a
product as well as a driver of reform and
the evidence-based paradigm, by setting
impossible prerequisite standards, and
by shifting the goalposts once evidence
is forthcoming, can be used as a weapon
to frustrate and delay overdue reform in
a manner that would be unacceptable in
other branches of medicine (99).
In better understanding this phe-
nomenon, it is worthwhile to reflect on
how innovation and reform in health
care works. Diffusion of innovations is
a major challenge in all industries, from
agriculture to manufacturing. The study
of diffusion of innovation has a long
history in the social sciences. Many na-
tions have established centres and strat-
egies to understand and promote this in
health care (100,101).
There are many contextual factors
involved, but there are also predictable
characteristics of individuals and health
care systems which influence the process
(102). Firstly, we must consider percep-
tions of the innovation. There must be
perceived benefit; the innovation should
be compatible with the values and needs
of those considering it. It should be sim-
ple or capable of simplification and, in
the process of spread, it is vital that in-
novations be adapted and reinvented in
relation to local needs. Secondly, there
are several groups of adopters involved
in the process of innovation. The inno-
vators are the smallest group and create
the novel ideas and skills. They are nov-
elty seekers who form wider national
and international networks or cliques
148-156.indd 153 29-09-2008 8:39:05
World Psychiatry 7:3 - October 2008
and they invest energy in these connec-
tions. They may be thought of as mav-
ericks heavily invested in a specialized
issue. The early adopters are a larger
group of opinion leaders who draw on
the innovators and cross-pollinate with
one another. They are open to a range
of new ideas and have the resources and
risk tolerance to try new things. Most
importantly, they are closely watched by
the next group, the early majority, who
are more local in their focus and more
risk averse. The early majority look to
the early adopters for guidance about
what is safe to try. The fourth group, the
late majority, are even more conservative
and look to the early majority, adopting
an innovation only when it appears to be
the new status quo. Finally, we have the
laggards, apparent members of a mod-
ern day flat earth society, whose point
of reference is the past. To be fair, this
description underestimates their value,
since they usefully point to the need to
retain some valuable elements of current
and prior practice. However, they are
also exposed defending the indefensible
and demanding impossible and unre-
alistic levels of evidence before accept-
ing change. Furthermore, the evidence
standards demanded for innovations are
rarely if ever applied to the status quo,
which in mental health at least is typi-
cally less evidence-based than the new
approach. This active rearguard action
is aided and abetted by the tendency of
systems to rapidly build inertia and rein-
stitutionalize after periods of progress.
Despite the welcome progress in ear-
ly intervention, the laggards have been
prominent in the early intervention
field. While evidence-based medicine is
by far the best antidote for taking wrong
and potentially dangerous and waste-
ful turns in health care, opponents of
change have been observed to misuse
the paradigm to frustrate change which
is overdue and in the best interests of
the community. There is regrettably in-
sufficient debate about where the onus
of proof lies in such matters, and what
considerations other than evidence
should influence decisions, especially
where changes have high face valid-
ity, such as emergency care and indeed
early intervention. Finally, it is unlikely
that oncologists would debate the rela-
tive value of early diagnosis and pallia-
tive care, which is where psychiatry has
got stuck repeatedly.
Berwick points out that the dissemi-
nation of innovation has a tipping point
(103), usually around 15-20% adoption.
Certainly, once the early majority have
swung in behind an innovation, the late
majority are likely to feel comfortable to
move as well. This is a process that can
be facilitated by several strategies. These
include identifying sound innovations,
leading by example, supporting innova-
tors and early adopters with resources
and time, making the activities of early
adopters highly visible, and valuing re-
invention as a form of learning rather
than requiring exact replication of in-
Many of the obstacles to early inter-
vention are the same ones which im-
pede progress in mental health more
widely, as illustrated in the Lancet Series
on Global Mental Health (104). They
include stigma, pessimism, the silence
that surrounds the mentally ill, and a
consequent failure to invest. Developed
and rapidly developing countries need
to recognize the public health impor-
tance of untreated and poorly treated
mental disorders. A key aspect which is
beginning to be recognized is that men-
tal disorders are the chronic diseases of
the young (105). Most adult type mental
disorders − notably psychotic, mood,
anxiety, substance use and personality
disorders have their onset and maxi-
mum impact in late adolescence and
early adult life. A broader focus for early
intervention would solve many of the
second order issues raised by the early
psychosis reform process, such as di-
agnostic uncertainty despite a clear-cut
need for care, stigma and engagement,
and should be more effective in mobi-
lizing community support for invest-
ment and reform in mental health. This
is occurring in Australia (106,107) and
Ireland (108), and is attracting increas-
ing attention in a number of other coun-
tries, along the lines of the innovation
process described above. It currently
represents a vital and challenging proj-
ect for early adopters in global psychia-
try to consider.
1. Vos T, Begg S. Victorian Burden of Disease
Study: morbidity. Melbourne: Public Health
Division, Department of Human Services,
2. Zubin J, Oppenheimer G, Neugebauer R.
Degeneration theory and the stigma of schi-
zophrenia. Biol Psychiatry 1985;20:1145-8.
3. McGorry P. Welcome to early intervention
in psychiatry. Early Int Psychiatry 2007;1:
4. Saraceno B. New knowledge and new hope
to people with emerging mental disorders.
Early Int Psychiatry 2007;1:3-4.
5. Insel TR. The arrival of preemptive psychia-
try. Early Int Psychiatry 2007;1:5-6.
6. Crow TJ, MacMillan JF, Johnson AL et al.
A randomised controlled trial of prophy-
lactic neuroleptic treatment. Br J Psychiatry
7. Lieberman JA, Alvir JM, Woerner M et al.
Prospective study of psychobiology in first-
episode schizophrenia at Hillside Hospital.
Schizophr Bull 1992;18:351-71.
8. Kane JM, Rifkin A, Quitkin F et al. Flu-
phenazine vs placebo in patients with re-
mitted, acute first-episode schizophrenia.
Arch Gen Psychiatry 1982;39:70-3.
9. McGorry PD, Edwards J, Mihalopoulos
C et al. EPPIC: an evolving system of early
detection and optimal management. Schizo-
phr Bull 1996;22:305-26.
10. Edwards J, McGorry PD. Implementing
early intervention in psychosis: a guide to
establishing early psychosis services. Lon-
don: Dunitz, 2002.
11. International Early Psychosis Association
Writing Group. International clinical prac-
tice guidelines for early psychosis. Br J Psy-
chiatry 2005;187(Suppl. 48):s120-4.
12. National Institute of Clinical Excellence.
Schizophrenia: full national clinical guide-
line on core interventions in primary and
secondary care. London: Gaskell and the
British Psychological Society, 2003.
13. Royal Australian and New Zealand College
of Psychiatrists Clinical Practice Guidelines
Team for the Treatment of Schizophrenia
and Related Disorders. Royal Australian
and New Zealand College of Psychiatrists
clinical practice guidelines for the treatment
of schizophrenia and related disorders.
Aust N Zeal J Psychiatry 2005;39:1-30.
14. Craig TK, Garety P, Power P et al. The
Lambeth Early Onset (LEO) Team: ran-
domised controlled trial of the effectiveness
of specialised care for early psychosis. BMJ
15. Jeppesen P, Petersen L, Thorup A et al. In-
tegrated treatment of first-episode psycho-
148-156.indd 154 29-09-2008 8:39:05
World Psychiatry 7:3 - October 2008
sis: effect of treatment on family burden:
OPUS trial. Br J Psychiatry 2005;187(Suppl.
16. Petersen L, Nordentoft M, Jeppesen P et al.
Improving 1-year outcome in first-episode
psychosis: OPUS trial. Br J Psychiatry 2005;
187(Suppl. 48):s98-103.
17. Thorup A, Petersen L, Jeppesen P et al.
Integrated treatment ameliorates negative
symptoms in first episode psychosis results
from the Danish OPUS trial. Schizophr Res
18. Johannessen JO, Larsen TK, Joa I et al.
Pathways to care for first-episode psychosis
in an early detection healthcare sector: part
of the Scandinavian TIPS study. Br J Psy-
chiatry 2005;187(Suppl. 48):s24-8.
19. Larsen TK, Melle I, Auestad B et al. Early
detection of first-episode psychosis: the
effect on 1-year outcome. Schizophr Bull
20. Melle I, Johannesen JO, Svein Friis S et
al. Early detection of the first episode of
schizophrenia and suicidal behavior. Am J
Psychiatry 2006;163:800-4.
21. Melle I, Larsen TK, Haahr U et al. Reduc-
ing the duration of untreated first-episode
psychosis: effects on clinical presentation.
Arch Gen Psychiatry 2004;61:143-50.
22. Mihalopoulos C, Harris M, Henry L et al.
Are the short-term cost savings and ben-
efits of an early psychosis program main-
tained at 8-year follow-up? Schizophr Bull
23. Mihalopoulos C, McGorry PD, Carter RC.
Is phase-specific, community-oriented treat-
ment of early psychosis an economically vi-
able method of improving outcome? Acta
Psychiatr Scand 1999;100:47-55.
24. Henry LP, Amminger GP, Harris MG et al.
The EPPIC long term follow up study of
frist episode psuchosis: clinical and func-
tional long term outcome. Submitted for
25. Rosenbaum B, Valbak K, Harder S et al.
Treatment of patients with first-episode
psychosis: two-year outcome data from the
Danish National Schizophrenia Project.
World Psychiatry 2006;5:100-3.
26. Jackson HJ, McGorry PD. The recogni-
tion and management of early psychosis: a
preventive approach, 2nd ed. Cambridge:
Cambridge University Press (in press).
27. McGorry PD, Hickie IB, Yung AR et al.
Clinical staging of psychiatric disorders: a
heuristic framework for choosing earlier,
safer and more effective interventions. Aust
N Zeal J Psychiatry 2006;40:616-22.
28. Schimmelmann BG, Conus P, Edwards J
et al. Diagnostic stability 18 months after
treatment initiation for first-episode psy-
chosis. J Clin Psychiatry 2005;66:1239-46.
29. Bromet EJ, Naz B, Fochtmann LJ et al.
Long-term diagnostic stability and out-
come in recent first-episode cohort studies
of schizophrenia. Schizophr Bull 2005;31:
30. Fennig S, Craig TJ, Bromet EJ. The consis-
tency of DSM-III-R delusional disorder in
a first-admission sample. Psychopathology
31. Fennig S, Bromet E, Galambos N et al. Di-
agnosis and six-month stability of negative
symptoms in psychotic disorders. Eur Arch
Psychiatry Clin Neurosci 1996;246:63-70.
32. Yung AR, Phillips LJ, Yuen HP et al. Psy-
chosis prediction: 12-month follow up of a
high-risk (“prodromal”) group. Schizophr
Res 2003;60:21-32.
33. Singh SP, Burns T, Amin S et al. Acute and
transient psychotic disorders: precursors,
epidemiology, course and outcome. Br J
Psychiatry 2004;185:452-9.
34. McGorry PD, Yung AR, Phillips LJ. The
“close-in” or ultra high-risk model: a safe
and effective strategy for research and clini-
cal intervention in prepsychotic mental dis-
order. Schizophr Bull 2003;29:771-90.
35. Kim Y. Renaming the term schizophrenia in
Japan. Lancet 2002;360:879.
36. McGorry PD. Issues for DSM-V: clinical
staging: a heuristic pathway to valid noso-
logy and safer, more effective treatment in
psychiatry. Am J Psychiatry 2007;164:859-
37. Fava G, Kellner R. Staging: a neglected di-
mension in psychiatric classification. Acta
Psychiatr Scand 1993;87:225-30.
38. McGorry PD, Mihalopoulos C, Henry L et
al. Spurious precision: procedural validity
of diagnostic assessment in psychotic disor-
ders. Am J Psychiatry 1995;152:220-3.
39. van Os J, Hanssen M, Bijl RV et al. Preva-
lence of psychotic disorder and community
level of psychotic symptoms: an urban-ru-
ral comparison. Arch Gen Psychiatry 2001;
40. Shoval G, Sever J, Sher L et al. Substance
use, suicidality, and adolescent-onset schizo-
phrenia: an Israeli 10-year retrospective
study. J Child Adolesc Psychopharmacol
41. Weiser M, Knobler HY, Noy S et al. Clinical
characteristics of adolescents later hospi-
talized for schizophrenia. Am J Med Genet
42. Craddock N, Owen MJ. Rethinking psy-
chosis: the disadvantages of a dichotomous
classification now outweigh the advantages.
World Psychiatry 2007;6:84-91.
43. McGorry PD, Copolov DL, Singh BS.
Current concepts in functional psychosis.
The case for a loosening of associations.
Schizophr Res 1990;3:221-34.
44. Yung AR, McGorry PD. The prodromal
phase of first-episode psychosis: past and
current conceptualizations. Schizophr Bull
45. Cornblatt B, Lencz T, Obuchowski M. The
schizophrenia prodrome: treatment and
high-risk perspectives. Schizophr Res 2002;
46. Mrazek PJ, Haggerty RJ. Reducing risks for
mental disorders: frontiers for preventive
intervention research. Washington: Nation-
al Academy Press, 1994.
47. Cornblatt BA, Auther AM. Treating early
psychosis: who, what, and when? Dialogues
in Clinical Neuroscience 2005;7:39-49.
48. Haroun N, Dunn L, Haroun A et al. Risk
and protection in prodromal schizophre-
nia: ethical implications for clinical practice
and future research. Schizophr Bull 2006;
49. Olsen KA, Rosenbaum B. Prospective in-
vestigations of the prodromal state of
schizophrenia: review of studies. Acta Psy-
chiatr Scand 2006;113:247-72.
50. Warner R. The prevention of schizophre-
nia: what interventions are safe and effec-
tive? Schizophr Bull 2001;27:551-62.
51. Warner R. Problems with early and very
early intervention in psychosis. Br J Psy-
chiatry 2005;187(Suppl. 48):s104-7.
52. Yung AR, Yuen HP, Berger G et al. Declin-
ing transition rate in Ultra High Risk (pro-
dromal) services: dilution or reduction of
risk? Schizophr Bul 2007;33:673-81.
53. McGorry PD, Killackey EJ. Early interven-
tion in psychosis: a new evidence based
paradigm. Epidemiologia e Psichiatria So-
ciale 2002;11:237-47.
54. Yung AR, Killackey E, Hetrick SE et al. The
prevention of schizophrenia. Int Rev Psy-
chiatry 2007;19:633-46.
55. Hafner H, Maurer K. Early detection of
schizophrenia: current evidence and fu-
ture perspectives. World Psychiatry 2006;5:
56. Sullivan H. The onset of schizophrenia.
Am J Psychiatry 1927;6:105-34.
57. Yung AR, McGorry PD, McFarlane CA et
al. Monitoring and care of young people at
incipient risk of psychosis. Schizophr Bull
58. Cannon TD, Cadenhead K, Cornblatt B et
al. Prediction of psychosis in youth at high
clinical risk: a multisite longitudinal study in
North America. Arch Gen Psychiatry 2008;
59. Yung AR, Yuen HP, McGorry PD et al.
Mapping the onset of psychosis: the com-
prehensive assessment of at-risk mental
states. Aust N Zeal J Psychiatry 2005;39:
60. McGlashan TH, Zipursky RB, Perkins D
et al. Randomized, double-blind trial of
olanzapine versus placebo in patients pro-
dromally symptomatic for psychosis. Am J
Psychiatry 2006;163:790-9.
61. McGorry PD, Yung AR, Phillips LJ et al.
Randomized controlled trial of interven-
tions designed to reduce the risk of progres-
sion to first-episode psychosis in a clinical
sample with subthreshold symptoms. Arch
Gen Psychiatry 2002;59:921-8.
62. Morrison AP, French P, Walford L et al.
Cognitive therapy for the prevention of
psychosis in people at ultra-high risk: ran-
domised controlled trial. Br J Psychiatry
148-156.indd 155 29-09-2008 8:39:05
World Psychiatry 7:3 - October 2008
63. Berger G, Dell’Olio M, Amminger P et al.
Neuroprotection in emerging psychotic dis-
orders. Early Int Psychiatry 2007;1:114-27.
64. Amminger G, Schaefer M, Papageorgiou K
et al. Omega-3 fatty acids reduce the risk of
early transition to psychosis in ultra-high
risk individuals: a double-blind random-
ized, placebo-controlled treatment study.
Schizophr Bull 2007;33:418-9.
65. Portland Identification and Early Refer-
ral Project. PIER project overview. www.
66. McGorry PD, Yung AR, Bechdolf A et al.
Back to the future: predicting and reshap-
ing the course of psychotic disorder. Arch
Gen Psychiatry 2008;65:25-7.
67. Cornblatt BA, Lencz T, Smith CW et al.
Can antidepressants be used to treat the
schizophrenia prodrome? Results of a
prospective, naturalistic treatment study
of adolescents. J Clin Psychiatry 2007;68:
68. Killackey E, Yung AR. Effectiveness of
early intervention in psychosis. Curr Opin
Psychiatry 2007;20:121-5.
69. McGorry PD. The specialist youth mental
health model: strengthening the weakest
link in the public mental health system.
Med J Australia 2007;187(Suppl. 7):s53-6.
70. McGorry PD, Killackey E, Yung AR. Early
intervention in psychotic disorders: detec-
tion and treatment of the first episode and
the critical early stages. Med J Australia
2007;187(Suppl. 7):s8-10.
71. Patel V, Araya R, Chatterjee S et al. Treat-
ment and prevention of mental disorders
in low-income and middle-income coun-
tries. Lancet 2007;370:991-1005.
72. Patton GC, Hetrick SE, McGorry P. Ser-
vice responses for youth onset mental dis-
orders. Curr Opin Psychiatry 2007;20:319-
73. McGlashan TH. Duration of untreated
psychosis in first-episode schizophrenia:
marker or determinant of course? Biol
Psychiatry 1999;46:899-907.
74. Marshall M, Lewis S, Lockwood A et al.
Association between duration of untreat-
ed psychosis and outcome in cohorts of
first-episode patients: a systematic review.
Arch Gen Psychiatry 2005;62:975-83.
75. Perkins DO, Gu H, Boteva K et al. Rela-
tionship between duration of untreated
psychosis and outcome in first-episode
schizophrenia: a critical review and meta-
analysis. Am J Psychiatry 2005;162:1785-
76. Bottlender R. Against: “Every person with
schizophrenia should be treated as early as
possible”. Psychiatr Prax 2006;33:106-7.
77. Harris MG, Henry LP, Harrigan SM et al.
The relationship between duration of un-
treated psychosis and outcome: an eight-
year prospective study. Schizophr Res
78. Kahn RS, Fleischhacker WW, Boter H et
al. Effectiveness of antipsychotic drugs in
first-episode schizophrenia and schizo-
phreniform disorder: an open randomised
clinical trial. Lancet 2008;371:1085-97.
79. Lieberman J, Stroup TS, McEvoy JP et al.
Effectiveness of antipsychotic drugs in pa-
tients with chronic schizophrenia. N Engl
J Med 2005;353:1209-23.
80. Perez-Iglesias R, Crespo-Facorro B, Mar-
tinez-Garcia O et al. Weight gain induced
by haloperidol, risperidone and olanzap-
ine after 1 year: findings of a randomized
clinical trial in a drug-naive population.
Schizophr Res 2008;99:13-22.
81. Jackson HJ, McGorry PD, Killackey E et
al. The ACE project: a randomised con-
trolled trial of CBT versus befriending for
first episode psychosis: acute phase and
one-year follow-up results. Psychol Med
82. Lewis SW, Tarrier N, Haddock G et al. A
randomised controlled trial of cognitive
behaviour therapy in early schizophrenia:
acute phase outcomes. Br J Psychiatry
2002; 181(Suppl. 43):s91-7.
83. Killackey E, Jackson HJ, McGorry PD.
Vocational intervention in first-episode
psychosis: a randomised controlled trial
of individual placement and support ver-
sus treatment as usual. Br J Psychiatry (in
84. Killackey EJ, Jackson HJ, Gleeson J et al.
Exciting career opportunity beckons! Ear-
ly intervention and vocational rehabilita-
tion in first episode psychosis: employing
cautious optimism. Aust N Zeal J Psychia-
try 2006;40:951-62.
85. Farkas M. The vision of recovery today:
what it is and what it means for services.
World Psychiatry 2007;6:68-74.
86. Velligan DI, Kern RS, Gold JM. Cognitive
rehabilitation for schizophrenia and the
putative role of motivation and expectan-
cies. Schizophr Bull 2006;32:474-85.
87. Joa I, Johannessen JO, Auestad B et al.
The key to reducing duration of untreated
first psychosis: information campaigns.
Schizophr Bull 2008;34:466-72.
88. Malla A, Norman R, Scholten D et al. A
community intervention for early identi-
fication of first episode psychosis: impact
on duration of untreated psychosis (DUP)
and patient characteristics. Soc Psychiatry
Psychiatr Epidemiol 2005;40:337-44.
89. Killackey E, McGorry PD. Interventions
in the early stages of psychosis. Psychiatr
Ann (in press).
90. Pharoah F, Mari J, Rathbone J et al. Fam-
ily intervention for schizophrenia. Co-
chrane Database of Systematic Reviews
91. Birchwood M, Fiorillo A. The critical pe-
riod for early intervention. Psychiatric Re-
habilitation Skills 2000;4:182-98.
92. McGorry PD. Early psychosis reform: too
fast or too slow? Acta Psychiatr Scand
93. Killackey EJ, Yung AR, McGorry PD.
Early psychosis: where we’ve been, where
we have to go. Epidemiologia e Psichiatria
Sociale 2007;16:102-8.
94. Nordentoft M, Jeppesen P, Abel M et al.
OPUS study: suicidal behaviour, suicidal
ideation and hopelessness among patients
with first-episode psychosis. One-year fol-
low-up of a randomised controlled trial. Br
J Psychiatry 2002;187(Suppl. 43):s98-106.
95. Bertelsen M, Jeppesen P, Petersen L et al.
Suicidal behaviour and mortality in first-
episode psychosis: the OPUS trial. Br J
Psychiatry 2007;191(Suppl. 51):s140-6.
96. McGorry PD, Yung AR. Early interven-
tion in psychosis: an overdue reform. Aust
N Zeal J Psychiatry 2003;37:393-8.
97. Lin V, Gibson B. Evidence-based health
policy. Oxford: Oxford University Press,
98. Russell J, Greenhalgh T, Byrne E et al.
Recognising rhetoric in health care pol-
icy analysis. J Health Serv Res Pol 2008;
99. McGorry PD. Evidence based reform of
mental health care. BMJ 2005;331:586-7.
100. National Health and Medical Research
Council. National Institute of Clinical
Studies. www.nhmrc.gov.au.
101. National Health Service. National Insti-
tute of Health and Clinical Excellence.
102. Berwick DM. The science of improve-
ment. JAMA 2003;299:1182-4.
103. Gladwell M. The tipping point. London:
Little Brown and Company, 2000.
104. Horton R. Launching a new movement
for mental health. Lancet 2007;370:806.
105. Insel TR, Fenton WS. Psychiatric epidemi-
ology: it’s not just about counting anymore.
Arch Gen Psychiatry 2005;62:590-2.
106. Headspace. Headspace: Australia’s Na-
tional Youth Mental Health Foundation.
107. McGorry PD, Purcell R, Hickie IB et al.
Investing in youth mental health is a best
buy. Med J Aust 2007;187(Suppl. 7):S5-7.
108. Headstrong. Headstrong: The National
Centre for Youth Mental Health. www.
148-156.indd 156 29-09-2008 8:39:06
    • "The rationale for targeting EIP patients in particular is that there is also good reason to believe that motivation to change patterns of cannabis and other substance use is high in this cohort [15]. Secondly, EIP is a form of secondary preventative care [47], with the aim of preventing or attenuating the risk of relapse to improve long-term prognosis. Given the substantial evidence base linking cannabis use to higher rates of relapse, reducing cannabis use in EIP services is consistent with EIP aims. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Around 35–45 % of people in contact with services for a first episode of psychosis are using cannabis. Cannabis use is associated with delays in remission, poorer clinical outcomes, significant increases in the risk of relapse, and lower engagement in work or education. While there is a clear need for effective interventions, so far only very limited benefits have been achieved from psychological interventions. Contingency management (CM) is a behavioural intervention in which specified desired behavioural change is reinforced through financial rewards. CM is now recognised to have a substantial evidence base in some contexts and its adoption in the UK is advocated by the National Institute for Health and Care Excellence (NICE) guidance as a treatment for substance or alcohol misuse. However, there is currently little published data testing its effectiveness for reducing cannabis use in early psychosis. MethodsCIRCLE is a two-arm, rater-blinded randomised controlled trial (RCT) investigating the clinical and cost-effectiveness of a CM intervention for reducing cannabis use among young people receiving treatment from UK Early Intervention in Psychosis (EIP) services. EIP service users (n = 544) with a recent history of cannabis use will be recruited. The experimental group will receive 12 once-weekly CM sessions, and a voucher reward if urinalysis shows that they have not used cannabis in the previous week. Both the experimental and the control groups will be offered an Optimised Treatment as Usual (OTAU) psychoeducational package targeting cannabis use. Assessment interviews will be performed at consent, at 3 months, and at 18 months. The primary outcome is time to relapse, defined as admission to an acute mental health service. Secondary outcomes include proportion of cannabis-free urine samples during the intervention period, severity of positive psychotic symptoms, quality-adjusted life years, and engagement in work or education. DiscussionCIRCLE is a RCT of CM for cannabis use in young people with a recent history of psychosis (EIP service users) and recent cannabis use. It is designed to investigate whether the intervention is a clinically and cost-effective treatment for cannabis use. It is intended to inform future treatment delivery, particularly in EIP settings. Trial registrationISRCTN33576045: doi 10.1186/ISRCTN33576045, registered on 28 November 2011.
    Full-text · Article · Dec 2016
    • "The onset of a psychotic disorder is typically preceded by a prodromal phase, known as the ultra high risk (UHR) state, involving the emergence of attenuated positive symptoms and a marked decline in functioning (Fusar-Poli et al., 2013; Yung et al., 1996 ). With the increasing appreciation of the clinical benefits of early intervention in psychosis (McGorry et al., 2008), a number of pharmacological and psychological treatments are being employed to delay or prevent the onset of the illness in people at UHR (Mechelli et al., 2015). Because approximately two-thirds of people who meet criteria for UHR will not develop the disorder , treatment that is intended to be preventative may be provided to individuals who may not actually need it. "
    [Show abstract] [Hide abstract] ABSTRACT: Recent studies have reported an association between psychopathology and subsequent clinical and functional outcomes in people at ultra-high risk (UHR) for psychosis. This has led to the suggestion that psychopathological information could be used to make prognostic predictions in this population. However, because the current literature is based on inferences at group level, the translational value of the findings for everyday clinical practice is unclear. Here we examined whether psychopathological information could be used to make individualized predictions about clinical and functional outcomes in people at UHR. Participants included 416 people at UHR followed prospectively at the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne, Australia. The data were analysed using Support Vector Machine (SVM), a supervised machine learning technique that allows inferences at the individual level. SVM predicted transition to psychosis with a specificity of 60.6%, a sensitivity of 68.6% and an accuracy of 64.6% (p<0.001). In addition, SVM predicted functioning with a specificity of 62.5%, a sensitivity of 62.5% and an accuracy of 62.5% (p=0.008). Prediction of transition was driven by disorder of thought content, attenuated positive symptoms and functioning, whereas functioning was best predicted by attention disturbances, anhedonia–asociality and disorder of thought content. These results indicate that psychopathological information allows individualized prognostic predictions with statistically significant accuracy. However, this level of accuracy may not be sufficient for clinical translation in real-world clinical practice. Accuracy might be improved by combining psychopathological information with other types of data using a multivariate machine learning framework.
    Full-text · Article · Dec 2016
    • "Efforts to establish criteria that identify individuals at highest risk for schizophrenia have had limited success (Yung et al., 2005; Cannon et al., 2008; McGorry et al., 2008 ). Recent work has attempted to improve predictive capability by supplementing current prodromal symptom criteria with neurocognitive measures (Brewer et al., 2005Brewer et al., , 2006 Keefe et al., 2006 ). "
    [Show abstract] [Hide abstract] ABSTRACT: The addition of off-the-shelf cognitive measures to established prodromal criteria has resulted in limited improvement in the prediction of conversion to psychosis. Tests that assess cognitive processes central to schizophrenia might better identify those at highest risk. The latent inhibition paradigm assesses a subject's tendency to ignore irrelevant stimuli, a process integral to healthy perceptual and cognitive function that has been hypothesized to be a key deficit underlying the development of schizophrenia. In this study, 142 young people at ultra high-risk for developing psychosis and 105 controls were tested on a within-subject latent inhibition paradigm. Additionally, we later inquired about the strategy that each subject employed to complete the test, and further investigated the relationship between reported strategy and the extent of latent inhibition exhibited. Unlike controls, ultra high-risk subjects did not demonstrate a significant latent inhibition effect. This difference between groups became greater when controlling for strategy. The lack of latent inhibition effect in our ultra high-risk sample suggests that individuals at ultra high-risk for psychosis are impaired in their allocation of attentional resources based on past predictive value of repeated stimuli. This fundamental deficit in the allocation of attention may contribute to the broader array of cognitive impairments and clinical symptoms displayed by individuals at ultra high-risk for psychosis.
    Full-text · Article · Dec 2016
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