Early intervention in psychosis: Concepts, evidence and future directions
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.
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).
DEVELOPMENT OF EARLY
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
148-156.indd 148 29-09-2008 8:39:04
World Psychiatry 7:3 - October 2008
Shift in thinking: pessimism
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
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
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
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.
ENHANCING THE VALUE
OF DIAGNOSIS: THE CLINICAL
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
148-156.indd 149 29-09-2008 8:39:04
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
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
What are the potential beneﬁts
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-
THE STAGES OF EARLY PSYCHOSIS
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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World Psychiatry 7:3 - October 2008
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
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).
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
148-156.indd 151 29-09-2008 8:39:05
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
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.
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-
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
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 PROCESS OF REFORM
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-
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