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Review

Randomized-controlled trials in people at ultra high risk of psychosis:

A review of treatment effectiveness

Antonio Preti a,, Matteo Cella b,1

a Centro Medico Genneruxi, Via Costantinopoli 42, 09129 Cagliari, Italyb King's College London, Institute of Psychiatry, Department of Psychological Medicine, Weston Education Centre, Cutcombe Rd, London SE5 9RJ, United Kingdom

a r t i c l e i n f o a b s t r a c t

Article histo ry:

Received 8 March 2010

Received in revised form 16 July 2010

Accepted 26 July 2010

Available online 21 August 2010

As an extension of the early intervention in psychosis paradigm, different focused treatments are

now offered to individuals at ultra high risk of psychosis (UHR) to prevent transition to schizo-

phrenia, however theeffectiveness of these treatments is unclear. A systematic literature search in

PubMed/Medline and PsycINFO was performed to deriveinformationon randomized control trials

(RCTs) in UHR samples. Seven reports were identied detailing results from ve independent

RCT studies. Two studies used antipsychotic drugs (one in combination with cognitive behavior

therapy); one study employed cognitive therapy; one study useda two-year programof intensive

community care with family psychoeducation; one study assessed the effectiveness of 3-months

omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) supplementation. Intensive community

care and the Omega-3 PUFAs supplementation were effective in reducing the transition to

psychosis at 12 months. Overall, rates of transition to psychosis at 1 year were 11% for focused

treatment groups (n =180) and 31.6% for control UHR groups (n=157). Receiving any of the

focused treatment was associated with a lower risk of developing psychosis if compared with notreatment or treatment as usual (Relative Risk=0.36; 95%CI: 0.220.59). Theavailableevidence at

2/3 years follow-up indicates that the effects of focused treatments are not stable after inter-

vention cessation and when treatment is delivered over a restricted time (e.g. 6 months or less),

it may achieve only a delay in psychosis onset. Due to the heterogeneity in the interventions

considered, the current results do not allow recommendation for any specic treatment.

2010 Elsevier B.V. All rights reserved.

Keywords:

Schizophrenia

Early intervention

High risk

Meta-analysis

Randomized-controlled trial

1. Introduction

Over the last fteen years, development of early, focused

treatment protocols for psychosis resurrected interest in the

prodromal phase of the disorder (for a review:Gross, 1997;Raballo et al., 2009). The proposed generalization of the

clinical staging paradigm to psychiatry, which is producing

excellent results in oncology and cardiovascular diseases, led

to the establishment of protocols of diagnosis and treatment

aimed at individuals presenting pre-psychotic symptoms that

might evolve into full-blown psychosis (McGorry, 2007;

Raballo and Lari, 2009).Yung and McGorry (1996)initially

characterized prodromic features of psychosis as an admix-

ture of anxiety, symptoms of depression and social difculties

but it was soon recognized that these symptoms were much

too generic to be highly predictive of the future onset of

psychosis. In Australia, the Personal Assessment and CrisisEvaluation (PACE) Clinic in Melbourne advanced a more

precise set of criteria to identify the so-calledultra high risk

(UHR) individuals. Currently, the prole of UHR individuals

corresponds to: a) Attenuated psychotic symptoms: i.e. sub-

threshold or attenuated psychotic symptoms during the past

year; or, b) Brief limited intermittent psychotic symptoms:

i.e. recurring brief episodes of frank psychotic symptoms

lasting no more than a week and spontaneously abating; or,

c) Genetic and familial risk factors: i.e. being diagnosed with

schizotypal personality disorder or having a rst-degree

relative with a psychotic disorder, and having experienced a

Schizophrenia Research 123 (2010) 3036

Corresponding author. Tel.: +39 070 480922.

E-mail addresses: [email protected] (A. Preti), [email protected] (M. Cella).1 Tel.: +44 20 322 83191.

0920-9964/$ see front matter 2010 Elsevier B.V. All rights reserved.doi:10.1016/j.schres.2010.07.026

Contents lists available at ScienceDirect

Schizophrenia Research

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signicant functional decrease in the last year (Yung et al.,

2003, 2004). Specic interviews were developed to diagnose

these prodromic symptoms, such as the Comprehensive

Assessment of At-Risk Mental States (Yung et al., 2005) and

the Structured Interview for Prodromal Syndromes/Scale of

Prodromal Symptoms (Miller et al., 2003). In Germany, Gross

and Huber developed alternative criteria based on the so-

called Basic Symptoms (BS), a list of anomalous subjective

experiences reported by patients during an active episode of

psychosis within the spectrum of schizophrenia (Huber et al.,

1979; Huber and Gross, 1989). After extensive psychometric

validation, a list of nine symptoms predictive of the risk of

psychosis was identied, and implemented in protocols of

early diagnosis (Klosterktter et al., 2005).

Individuals identied with UHR or BS criteria are currently

studied and their transition to psychosis investigated at

follow-up (Bechdolf et al., 2007; Klosterktter et al., 2001;

Yung et al., 2008). Different specic treatments have been

trialed for those recognized at higher risk (Edwards and

McGorry, 2002; Larsen et al., 2001; Cocchi et al., 2008). Past

reviews on the effectiveness of these treatments arrived at

inconclusive results (Olsen and Rosenbaum, 2006; Marshall

and Rathbone, 2006; de Koning et al., 2009), inpart due tothe

limited number of completed randomized control trials

(RCTs). However, more recently new RCT studies of people

at high risk of transition to psychosis have been published,

thus justifying a reconsideration of treatment effectiveness.

2. Methods

A literature search was conducted for RCTs evaluating

treatments aimed at preventing the development of a diag-

nosable psychotic episode in UHR or BS positive patients.

Studies were considered relevant if: they tested interventions'

effectiveness in reducing transition to psychosis; the specic

intervention was compared to a contrast group; assignment to

treatment was blind and randomized; transition to psychosis

was considered over a period of 12 months or more.

Studies on treatments and/or symptoms management

interventions designed for people in the early stages of

psychosis were excluded. Therefore all studies including

patients with one or more clinically relevant psychotic episode

were excluded. These studies differ in a signicant way from

prevention studies since they offer timely intervention after a

rst episode of psychosis has already been experienced.

The main outcome considered was transition rate to

psychosis in the high risk prospective cohort, de

ned on thebasis of the criteria used in each study (seeResults).

2.1. Search criteria and results

Both PubMed/Medline and PsycINFO were searched from

January 1990 to February 2010 (lastupdate: July 10th, 2010) by

MC andAP using the following keywords:psych*or schizo* and

risk or ultra and random* or trial or control* or RCT.

Only publications in English were considered. Abstracts of

retrieved papers were scanned to identify studies matching

the inclusion criteria. References of retrieved articles and

review on the topic (e.g. Olsen and Rosenbaum, 2006; de

Koning et al., 2009; McGorry et al., 2009) were also examinedto identify other possible relevant studies.

The search strategy conducted on PsychInfo identied 484

abstracts of which 56 referred to potentially eligible studies in

the at-risk population. All non-empirical studies, those not

delivering an intervention and those with a design different

from RCT were excluded, resulting in six articles that were

included in the analysis. Using the same terms we conducted

a search in PubMed/Medline and identied an initial pool of

581 studies. Using the same inclusion and exclusion criteria,

seven articles were identied and included in the nal

analysis. There was a complete overlap between the studies

identied with PsychInfo and PubMed/Medline. Further the

data presented in McGorry et al. (2002) and Phillips et al.

(2007)and those inMorrison et al. (2004, 2007)referred to

the same study, therefore ve independent studies were

included in the meta-analysis (Table 1).

One additional study, referenced in a topical review on

psychosis proneness by de Koning et al. (2009) was not

included due to lack of information (e.g. sample size). This

study investigated cognitive behavioral therapy (CBT) vs.

supportive counseling in high risk individuals diagnosed

according to BS criteria (Bechdolf et al., 2007). A further

study, aimed at evaluating the effectiveness of amisulpiride in

individuals at late prodromal state according to the BS criteria,

was excluded because reported only data on a 12-week follow-

up and did not assess transition to psychosis as an outcome

(Ruhrmann et al., 2007).

2.2. Analysis

Intervention effectiveness was investigated using meta-

analytic techniques. The meta-analysis is a technique used to

amalgamate and review previous quantitative research to

answer the question of whether the interventions considered

make a difference on a dependent variable. Lipsey and Wilson

(2001)suggest that for a good meta-analysis it is essential

that the analyst have a denition of the domain of interest

and a rationale for inclusion and exclusion of studies.

This study wants to test if proposing a specic interven-

tion to people who comply with the criteria for ultra high risk

of psychosis is better than offering treatment as usual or no

treatment. The conation of different treatment methods in

the same analysis has been conducted in previous research

and deemed valid. A classic example is the seminal meta-

analysis paper by Smith and Glass (1977) investigating the

effectiveness of different types of psychotherapy (e.g.

psychodynamic, gestalt).

Meta-analysis was carried out with Comprehensive Meta-Analysis (version 2.2) software (www.meta-analysis.com/).

In the pooled analysis, the Relative Risk (RR) was reported

with 95% Condence Interval (CI); for a result to be statistically

signicant, extremes of CI should not include the unit (i.e. both

of them should be above or below 1).

Measures of heterogeneity were the Cochran's Q and the I2

statistic, which assesses the extent of inconsistency among

the studies' results and is interpreted as approximately the

proportion of total variation in each study estimates inde-

pendent from sampling errors;I2 statistic of 50% or more was

taken to be indicative of moderate heterogeneity (Higgins et

al., 2003). According toEgger et al. (1997)funnel plots were

also inspected for evidence of asymmetry as a proxy measureof heterogeneity. Heterogeneity was further assessed with

31A. Preti, M. Cella / Schizophrenia Research 123 (2010) 3036
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the trim and ll method (Duval and Tweedie, 2000a,b). The

trim and ll method assumes the most extreme results go

unpublished, and recalculates the effect size by imputation ofthose missing studies, producing a symmetric funnel plot. A

smaller shift in the trim and ll adjusted effect size indicates a

good accuracy of the initial effect size.

In the case of statistically signicant result, the classical

fail-safe n was calculated: this is the minimum number of

additional null studies necessary to make the result no longer

signicant on a statistical ground (Rosenthal, 1979; Carson

et al., 1990).

3. Results

The trials selected for this study involved a variety andcombination of interventions and control conditions.

There were two trials based on medications:

- McGlashan et al. (2006)administered 515 mg olanzapine

daily for 1 year, compared to placebo;

- McGorry et al. (2002) administered low dosage antipsy-

chotic medication (12 mg of risperidone daily) in com-

bination with a six-month course of cognitive therapy.

Phillips et al. (2007)reported further follow-up data from

this study.

One trial was based on cognitive behavioral therapy:

- Morrison et al. (2004, 2007)developed a protocol to treat

UHR individuals, in line with the basic principles of CBT,

and compared this protocol to monitoring (i.e. no active

intervention). This six-month long intervention aimed to

develop a set of strategies to enhance symptom control

and to reduce associate distress by evaluating alternative

Table 1

RCT of focused treatment aimed at reducing the risk of transition to psychosis in people at high risk of psychosis.

Study Criteria for

diagnosis

Criteria

for outcome

Focused treatment

(FT)

Contrast group

(C)

Transition to psychosis

at 1 year*

Transition to psychosis

at more than 1 year*

McGorry et al., 2002;

Phillips et al., 2007

UHR criteria

according to

PACE criteria

based on the

CAARMS

Suprathreshold

levels of psychosis

Risperidone 12 mg+

CBT

Needs-based

intervention (?)

FT=6/31 (19.3%) Within 3/4 years

Duration= 6 months Duration= 6 months

C=10/28 (35.7%) FT=10/31 (32.2%)

N= 31 N= 28

C=12/28 (42.8%)

Dropout=none Dropout=none

Dropout=18 (7/11)

Morrison et al., 2004;

Morrison et al.,

2007

UHR criteria

equivalent

to PACE

criteria

based on

PANSS

Transition to

psychosis using

cut-off points on

PANSS

CT Monitoring Within 3 yearsFT=2/35 (5.7%)

Duration=6 months Duration=6 months C=5/23 (21.7%) FT=7/35 (20.0%)

N= 35 N= 23 C = 7/23 (30.4%)

Dropout = 9 Dropout = 7 Dropout = 31 (18/13)

McGlashan et al.

(2006)

UHR criteria

based on the

SIPS

Conversion to

psychosis

according to the

Presence of

Psychosis Scale

Olanzapine 515 mg Placebo Within 2 yearsFT=5/31 (16.1%)

Duration= 12 months Duration=12 months C= 11/29 (37.9%) FT=8/31 (25.8%)

N= 31 N= 29 C = 13/29 (44.8%)

Dropout = 14 Dropout = 19 Dropout = none

Nordentoft et al.

(2006)

ICD-10

criteria for

Schizotypal

disorder

ICD-10 diagnosis

of a psychotic

disorder within

the F2 spectrum

Raters were not

blind

Intensive treatment

with family

intervention

Standard care Within 2 yearsFT=3/37 (8.1%)

Duration=24 months C= 10/30 (33.3%) FT=9/36 (25.0%)

Duration= 24 months

N= 37 C = 14/29 (48.2%)

N= 42

Dropout = 7 Dropout = 14 (6/8)

Dropout=5

Amminger et al.

(2010)

UHR criteria

equivalent

to PACE

criteria

based on

PANSS

Transition to

psychosis using

cut-off points on

PANSS

Omega-3 PUFAs 1.2 g Placebo

Duration= 3 months Duration= 3 months

FT=2/41 (4.8%)

N= 41 N= 40

C=11/40 (27.5%)

Dropout = 3 Dropout = 2

Abbreviations and explanations:

PACE=Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne.

CAARMS=Comprehensive Assessment of At-Risk Mental States.

PANSS=Positive and Negative Syndrome Scale.

SIPS=Structured Interview for Prodromal Syndromes, which operationally denes the PACE UHR criteria.

ICD-10= International Classication of Diseases, tenth edition, World Health Organization.

CBT=Cognitive Behavioral Therapy.

CT= Cognitive Therapy.PUFAs=Polyunsaturated Fatty Acids.

Suprathreshold levels of psychosis: a score of 3 or more on thehallucinations subscale, a score of 4 or more on theunusual thought content subscale (plus a score 3

for delusional conviction on the Comprehensive Assessment of Symptoms and History), or a score of 4 or more on the conceptual disorganization subscale of the

Brief Psychiatric Rating Scale; all for a duration greater than 1 week.

Transition to psychosis using cut-off points on PANSS: 4 or more on hallucinations, 4 or more on delusions and 5 or more on conceptual disorganization; all for a

duration greater than 1 week.

Conversion to psychosis according to the Presence of Psychosis Scale: any psychotic disorder in the DSM-IV schizophrenia spectrum on the basis of scores on the

Presence of Psychosis Scale (unspecied threshold).

*Data on transition to psychosis are on a intention-to-treat basis.

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explanations, decatastrophize fears and testing hypothe-

ses using behavioral experiments.

One trial was based on intensive community care:

- Nordentoft et al. (2006) used a two-year community

treatment intervention based on: home visits, regular

assessments, psycho-educational components, social skills

training and substance abuse aid. In this study the

comparison group was provided with treatment as usual.

One trial was based on dietary supplementation:

- Amminger et al. (2010)administered a daily dose of 1.2 g

omega-3 polyunsaturated fatty acids (Omega-3 PUFAs)

for 12 weeks. The omega-3 group was compared with a

placebo group prescribed with coconut oil (polyunsatu-

rated fatty acids free). The placebo also contained vitamin

E and 1% sh oil to mimic taste of the active treatment.

Denition of the transition to psychosis was based on cut-

off points on previously validated symptom scales. Threshold

levels based on the Brief Psychiatric Rating Scale were used in

the PACE study (McGorry et al., 2002; Phillips et al., 2007).

Morrison et al. (2004, 2007) and Amminger et al. (2010)

used an adaptation of these threshold levels to the Positive

and Negative Syndrome Scale. Finally, McGlashan et al.

(2006) used an ad hoc scale, the Presence of Psychosis

Scale (McGlashan et al., 2003) developed specically to full

the lack of DSM-IV-dened criteria for psychosis onset

(p. 791).

In addition, the PACE group (McGorry et al., 2002; Phillips et

al., 2007) and the Early Detection and Intervention Evaluation

study (Morrison et al., 2004, 2007) used formal diagnostic

criteria for psychosis according the DSM-IV (APA, 1994), while

the OPUS trial (Nordentoft et al., 2006) used ICD-10 diagnostic

criteria (WHO, 1992).

Data on dropout were reported in all the studies considered.

A priori power analysis was included in 2 studies only: in one

case without details on parameters (Nordentoft et al., 2006)

and in the other case (Amminger et al., 2010) using unusual

parameters (1-beta, i.e. power=0.70 rather than 0.80; a too

high expected reduction of the risk, i.e. 50%, for the specic

treatment). In all studies, blinding to assessors was difcult to

maintain, since differences in treatment were evident, for

example, on the basis of side effects.

3.1. Treatment effectiveness

Twenty-four months program of intensive treatment with

family intervention (Nordentoft et al., 2006) and a 3 months

program of Omega-3 PUFAs supplementation(Amminger et al.,

2010) were found equally effective in reducing transition to

psychosis rate after 12 months. Pharmacological interventions

with antipsychotic drugs combined or not with CBT were

not found to be effective in reducing the transition rate to

psychosis in UHR people at 12 months. However there was a

trend for less people to be diagnosed with psychosis in all the

focused treatment compared with the contrast group (see

Table 1for details). Data on longer follow-up were available

only for four studies. There was a trend for intensive

community care and olanzapine to produce lower rates of

transition to psychosis compared with the contrast group at

24 month follow-up: 25.0% vs. 48.2% (Nordentoft et al., 2006)

and 25.8% vs. 44.8% (McGlashan et al., 2006), respectively. For

CT and CBT in combination with low dosage risperidone the

effects were less evident: 32.2% vs. 42.8% at 3/4 year follow-up

(Morrison et al., 2007) and 20.0% vs. 30.4% at 3 year follow-up

(Phillips et al., 2007).

3.2. Results of the meta-analysis

Table 2 shows the results of the pooled analysis. In all

studies the focused treatment yielded a reduced risk of

transition to psychosis over 12 months but in three of theve

studies the results were not signicant (on the basis of 95%

CI). When considered together, the pooled studies indicated a

signicant effect of the focused treatment over the contrast

group. This was evident in both the xed and random model

RR=0.364 (95%CI: 0.2220.599), favoring the focused spe-

ci

c intervention. Application of the trim and

ll method didnot modify this estimate.

Heterogeneity was absent: Q=2.296, df=4, p =0.682;

I2= 0%. Classical fail-safe value from the studies considered

was 18, which is rather strong (considering that it derives

only from ve studies).

The exclusion of theNordentoft et al. (2006)study, due to

the inclusion of patients with schizotypal disorder only, did

not change the nding favoring the focused specic inter-

vention in both the xed and random model RR=0.282 (95%

CI: 0.1420.560; Q=1.447, df=3,p =0.694; I2=0%); how-

ever, the classical fail-safe number dropped to 11, which is

still moderately good.

Table 2

Meta-analytic results for prospective randomized-controlled studies on transition to psychosis in people at high risk of psychosis.

Study Type of treatment Within 12 months Within 24/36 months

RR (95%CI) z-value p-value RR (95%CI) z-value p-value

McGorry et al., 2002; Phillips et al., 2007 Risperidone+ CBT 0.542 (0.2261.298) 1.374 0.169 0.753 (0.3871.465) 0.836 0.403

Morrison et al., 2004;Morrison et al., 2007 CT 0.263 (0.0561.242) 1.686 0.092 0.657 (0.2661.626) 0.908 0.364

McGlashan et al. (2006) Olanzapine 0.425 (0.1 681.076) 1.806 0.071 0.576 (0.2801.183) 1.502 0.133

Nordentoft et al. (2006) Intensive therapy 0.264 (0.0790.888) 2.152 0.031 0.566 (0.2781.153) 1.562 0.117

Amminger et al. (2010) Omega-3 PUFAs 0.177 (0.0420.750) 2.350 0.019

Fixed 0.364 (0.2220.599) 3.981 0.0001 0.636 (0.4400.919) 2.410 0.016

Random 0.364 (0.2220.599) 3.981 0.0001 0.636 (0.4400.919) 2.410 0.016

Trim and ll estimate 0.364 (0.2210.599) 0.635 (0.4400.918)

33A. Preti, M. Cella / Schizophrenia Research 123 (2010) 3036


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As noted, intervention effectiveness was not maintained

at the longer follow-ups, when the four studies reporting data

on transition to psychosis within 2 or more years were

considered individually. However, the pooled analysis still

found a statistically signicant effect favoring the focused

specic interventions: in both the xed and random model

RR=0.636 (95%CI=0.4400.919), again with no effect after

application of the trim and ll method, and no indication of

heterogeneity (Q=0.427, df=3, p =0.935; I2=0%). How-

ever on the basis of classical fail-safe value of 3 this is a very

unstable estimate and means that only three additional

studies with no signicant difference between active treat-

ment and contrast group would invalidate this nding.

Point estimates of transition to psychosis in the control

group, assuming that this is the effect of a non-specic

treatment unlikely to modify risk, was 31.6% (95%CI: 24.6%

39.6%) at 12 months and 42.0%(33.1%51.5%)at 24/36 months,

as against 11% (6.4%18.5%) and 25.8% (19.0%34.0%), respec-

tively, in the treated group.

4. Discussion

Focused treatments with people at high risk of psychosis

are effective in reducing the risk of transition to full-blown

psychosis over a 12 month period. Thisnding is robust, with

no heterogeneity across studies. However, over a longer

period (i.e. 2 years), interventions provided for a limited

time interval are less effective, resulting merely in a delay of

transition to psychosis.

Ourndings are in line with the result ofBechdolf et al.'s

(2006, 2008) RCT study, which was not included in this meta-

analysis due to lack of information on sample size in the two

contrasting groups. These authors found BS positive patients

who received a CBT intervention to be less likely than BS

positive patients who received supportive counseling to

exacerbate from early to late psychosis prodromal state (i.e.

a condition with attenuated psychotic symptoms) at both 12

(3.2% vs. 16.9%) and 24 month (6.3% vs. 20.0%) follow-up.

The heterogeneity of interventions considered, each with

distinct mechanisms by which a therapeutic effect might

occur, precludes any clear treatment recommendation.

However our results provide an empirical account for

strengthening the diagnostic criteria in early intervention

programs. The DSM-V will, most probably, include criteria for

the diagnosis of the prodromal phase of psychosis (Corcoran et

al., 2010). The DSM inclusion of formal criteria to diagnose the

at-risk state

of developing psychosis may improve thecomparability of studies and foster empirical challenges to the

denition that will be adopted.

When considering the current results some limitations

have to be considered. In all but theNordentoft et al. (2006)

study raters are described as blind to interventions. However,

in these studies blinding to assessors was difcult to maintain

and this is a serious limitation in randomized trials,

frequently exposing the results to bias. Also none of the

studies considered had a clear description of the method used

to generate the random allocation sequence or the procedure

used to test concealment (Schulz et al., 2010).

Pharmacotherapy based interventions with antipsychotic

drugs resulted in a higher proportion of patients developingpsychosis, when discontinued, compared to non-pharmaco-

logical intervention: 16.1% for olanzapine and 19.3% for

risperidone vs. 5.7% for cognitive therapy alone and 4.8% for

Omega-3 PUFAs supplementation.

Two naturalistic studies had already reported antipsy-

chotic treatment to be associated with higher rates of

transition to psychosis than other interventions (e.g. anti-

depressants, Cornblatt et al., 2007; Fusar-Poli et al., 2007).

The results of the reviewed RCTs suggest caution in

prescribing antipsychotic medication to individuals at-risk

of developing psychosis, due to noticeable (and potentially

permanent) side effects (e.g. Corcoran et al., 2005; Haddad

and Dursun, 2008; Odagaki, 2009). Also stigmatization and

self-stigmatization can arise by merely receiving a psychiatric

prescription or diagnosis, and evidence suggests that anti-

psychotic prescription can be considered more stigmatizing

than other interventions (Corcoran et al., 2005;Jenkins and

Carpenter-Song, 2009; Yang et al., 2010).

However, various research and clinical accounts showed that

individuals at high risk of transition to psychosis, dened with

UHR or the BS criteria, are generally suffering from multiple

mental and functional disturbances, and can benet from

appropriate psychiatric/psychological help (e.g. Ruhrmann

et al., 2010a,b). One major advantage in treating UHR individuals

would be the timely recognition and treatment of the rst

episode, resulting in a substantially shortened duration of

untreated psychosis, which can ultimately reduce the worst

outcomes of schizophrenia in term of personal and social costs,

morbidity and mortality (McGorry et al., 2009). In the studies

herewith reviewed, transition to psychosis in the control UHR

patients groups was 31% over 12 months and 42% over 24/

36 months. However, over a longer period (i.e. 9.5 years follow-

up), almost 50% of the patientspositive to theBS criteriareceived

a diagnosis of schizophrenia (Klosterktter et al., 2001).

Thecreation of shared criteria for diagnosis of the high risk

status and transition to psychosis is a prerequisite to achieve

more reliable and consistent results in this area ( Yung et al.,

2010; Ruhrmann et al., 2010a,b). Most studies included in this

review used the UHR criteria, but were variable as far as

criteria for transition to psychosis were concerned. Another

important aspect worth considering is that no study used

hard indicators of social functioning as outcome, such as

independent living vs. living with the birth family; being in

paid employment or studying vs. unemployment; having a

partner vs. being single. Moreover, the use of reliable and

valid scales with patients with full-blown psychosis (i.e. the

Brief Psychiatric Rating Scale or the Positive and Negative

Syndrome Scale) may not be adequate to measure symptomsin high risk individuals. Also dropouts should be more con-

sistently reported and the use of ad hoc parameters for power

analysis should be discouraged.

The evaluation of costs and implementation feasibility

would allow a more accurate comparison of the different

therapeutic approaches and will be valuable to inform service

delivery. Our results showed that a two-year long community

treatment program (Nordentoft et al., 2006) was effective in

reducing transition to psychosis rates, nevertheless this inter-

vention it is expected to be more costly than other treatments

delivered for shorter periods (e.g. 3 to 6 months). Long lasting

and more demanding interventions can be required only for

individuals with a severe prodromal presentation. In less severecases, CBT based approach may prove to be a successful and



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