Download - Outcome of An Early Intervention Programme for Psychosis (EASY): A Case Controlled Study

Final Report HHSRC«03040141»

HHSRF Health and Health Services Research Fund

«Outcome of an Early Intervention Programme for Psychosis (EASY):

A Case Controlled Study »

Submitted to the Grant Review Board (October 2008)

Investigator(s) Eric YH Chen1, Jennifer YM Tang1, Christy LM Hui1, CW Law2, Carol Yew1, Gloria HY Wong1,

Dicky WS Chung3, Cindy PY Chiu2, May Lam3, Steve Tso4, Kathy Chan5, KC Yip6, SF Hung5, Margaret Tay7 1. Department of Psychiatry, The University of Hong Kong, Hong Kong

2. Department of Psychiatry, Queen Mary Hospital, Hong Kong 3. Department of Psychiatry, Tai Po Hospital, Hong Kong

4. Department of Psychiatry, Castle Peak Hospital, Hong Kong 5. Department of Psychiatry, Kwai Chung Hospital, Hong Kong

6. Department of Psychiatry, Kowloon Hospital, Hong Kong 7. Hospital Authority, Head Office

Outcome of an early intervention programme for psychosis

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Content Acknowledgements..............................................................................................................................3 Summary ..............................................................................................................................................5 Introduction .........................................................................................................................................7 Aims and Objectives............................................................................................................................8 Methods ................................................................................................................................................9

Methodology .....................................................................................................................................9 Sample definition..............................................................................................................................9

Inclusion criteria .........................................................................................................................10 Exclusion criteria ........................................................................................................................10

Matching between cases and control.............................................................................................10 Data Acquisition Procedure and Analysis ....................................................................................10 Validity and Reliability ...................................................................................................................12

Results.................................................................................................................................................13 Demographics .................................................................................................................................13 Duration of untreated psychosis (DUP)........................................................................................14 Pharmacotherapy ...........................................................................................................................15 Outcome 1: Hospitalization ...........................................................................................................16 Outcome 2: Relapses and Symptoms.............................................................................................16 Outcome 3: Functioning................................................................................................................17 Outcome 4: Risk Behaviours .........................................................................................................20 Outcome 5: Disengagement ...........................................................................................................20 DUP and major outcomes ..............................................................................................................21

Discussion ...........................................................................................................................................21 Limitations .........................................................................................................................................23 Implications........................................................................................................................................23 Dissemination.....................................................................................................................................24 Publications ........................................................................................................................................24 Bibliography.......................................................................................................................................25 Financial Statement...........................................................................................................................28 Appendices .........................................................................................................................................29


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Acknowledgements

The study is fully funded by Health and Health Services Research Fund, by Food and Health

Bureau, Hong Kong Special Administration Region. The grant number is 03040141.

The authors would like to acknowledge all coordinating clinicians, all staff from the participating

Hospitals, Clinics, Medical Records Departments and research assistants, who helped in the medical

records review and data collection processes.

Coordinating Clinicians (listed in alphabetical order):

• Dr Kathy Chan (Kwai Chung Hospital)

• Dr Cindy PY Chiu (Queen Mary Hospital)

• Dr Dicky Chung (Tai Po Hospital)

• Dr Eva Dunn (Pamela Youde Nethersole Eastern Hospital)

• Dr CW Law (Queen Mary Hospital)

• Dr Steve Tso (Castle Peak Hospital)

• Dr KC Yip (Kowloon Hospital)

• Dr GC Yiu (United Christian Hospital)

Participating Hospitals, Clinics and Medical Records Department (listed in alphabetical order):

• Alice Ho Miu Ling Nethersole Hospital (Medical Records Department; Department of

Psychiatry)

• Castle Peak Hospital (Medical Records Unit)

• East Kowloon Psychiatric Centre

• Kowloon Hospital (Department of Psychiatry)

• Kwai Chung Hospital (Medical Records Office)

• North District Hospital (Medical Records Department)

• Pamela Youde Nethersole Eastern Hospital (Medical Records Office; Department of

Psychiatry)


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• Prince of Wales Hospital (Central Records Office; Department of Psychiatry)

• Princess Margaret Hospital (West Kowloon Psychiatric Centre; Kwai Chung Child and

Adolescent Psychiatric Centre; K10 Medical Records)

• Queen Mary Hospital (Department of Psychiatry)

• Shatin Hospital (Medical Records Office; Department of Psychiatry)

• Tai Po Hospital (Medical Records Office; Psychiatric Wards)

• Tuen Mun Hospital (Tuen Mun Mental Health Clinic)

• United Christian Hospital (Department of Psychiatry; Medical Records Department;

Psychiatric Wards)

• Western Psychiatric Centre

• Yaumatei Child Psychiatric Centre

• Yung Fung Shee Memorial Centre (Department of Psychiatry)

Research Staff

• Carol Yew, Joanna Wong, Cecilia AuYeung, Jennifer Tang, and Gloria Wong


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Summary

Early Intervention Services for Psychosis is an increasingly adopted approach to improve the

outcome for psychotic disorders (including schizophrenia and related disorders). Early psychosis

programmes usually consist of two major components: (1) early detection; (2) critical period

intervention. Early detection aims to reduce the delays in presentation of first psychotic episodes,

which are associated with poor long term outcome. Critical period intervention aims to optimize the

outcome in the first 2-3 years, and thereby producing a lasting favourable impact on the long term

outcome.

Early intervention services have been implemented in many locations worldwide. Hong

Kong has started one of the first early intervention programmes in Asia in 2001. The EASY (Early

Assessment Service for Young People with Psychosis) programme provides a territory-wide service

to young people with first-onset psychotic disorders between 15 and 25. Prior to the EASY

programme, general psychiatric care (Standard Care, SC) consists mainly of inpatient treatment of

the first psychotic episode, followed by relatively sparse outpatient follow-up with little

psychosocial support. The EASY service provides specialised multidisciplinary team to offer a

comprehensive package of intervention targeting the specific needs of patients and their carers at

this stage of the disorder. It uses a case-management approach and assertively follows first-episode

patients for 2 years after the initial episode.

The efficacy of the early intervention (EI) programme in Hong Kong has been evaluated by

a pilot study of a subpopulation within Hong Kong, and only for a follow-up period of 2 years. The

current study aims to extend the pilot study to include the entire population of Hong Kong for a

longer follow-up period of 3 years, with a control group (SC) that is well matched for gender,

diagnosis and age.

Based on the Psychiatric Case Register (PsyCIS), 700 EASY patients (EI, 2001-2003) were

matched with 700 Controls (SC, 1998-2001) on a one-to-one basis in respect of gender, diagnosis

and age. Relevant data for each case were retrieved from clinical records for the first three years

using a standardized and operationalized template. Key outcome variables (i.e., functioning,


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hospitalization, symptoms, suicide behaviour and relapse) were compared between these two groups.

As atypical antipsychotics were more extensively used in the period of the EI cohort, restrict

analysis, and co-variate analysis was conducted to separate the impacts of early intervention from

medication.

In addition to gender, diagnosis and age, the two groups were also well-matched for pre-

morbid functioning. EI had significantly more use in atypical antipsychotics. EI patients (M=62.1

days) were hospitalised less than SC patients (M=114.7 days). They also had a better functional

outcome (p < .001). The EI group had fewer disengagement from service (EI: 27.1%; SC: 34.3%),

suicides (EI: 1%; SC: 2.6%), suicide attempts (EI: 12.9%; SC: 19.9%), and aggressive behaviour

(EI: 12.4%; SC: 20.4%). These effects appear independent on medication and could be attributed

with the improved intervention programme. The frequency of relapses and the duration of untreated

psychosis (DUP) were similar between the groups, suggesting that in Hong Kong, the improved

outcome was not mediated by these two variables.

The present study suggests that early psychosis programme in Hong Kong is successful in

improving the 3-year outcome of psychotic disorders. The effect appears to be attributable to

improved intervention rather than to a reduction of DUP, relapses or atypical medication.


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Introduction

Patients with psychotic disorders are characterized by having a number of perceptual and thought

disturbances, particularly hallucinations, delusions and thought disorders. Psychotic disorders are

among the 10 leading causes of disability-adjusted life-years (DALYs) worldwide(1). The critical

period hypothesis proposed by Birchwood and colleagues(2) suggests that outcome is more

malleable to interventions in the early course of illness, in which clinical and social deterioration are

likely to occur in the first 2-3 years and reach a plateau thereafter. It closely links with the concept

of duration of untreated psychosis (DUP), which represents the time difference between the onset of

positive symptoms and the first presentation of psychiatric service. The longer time they stay

untreated, the greater chance they will have more self-harm behaviour and perform worse in

symptomatic recovery, social relations and functioning(3-8).This critical period offers chance for

early intervention, in the hope of improving both the short term and long term outcomes.

Reducing treatment delay is a central component in the development of early intervention

programme. A growing body of evidence has suggested that longer duration of untreated psychosis

(DUP) is associated with poorer functional, symptomatic outcome, and quality of life both in the

short term and medium term(6, 9). However, the importance of DUP in determining the treatment

outcome is still in debate(10-12) since the role of DUP as a prognostic predictor is not well-established

yet. The relationship between DUP and long-term outcome is still unclear(10).

Phase-specific case management is another core concept of early intervention programme,

but its role is not sufficiently evaluated in contrast with early detection. Comprehensive phase-

specific management involves biological, social and psychological interventions(13). However the

effectiveness of case management itself is not clear yet as early intervention programmes are

usually a combination of early detection and intensive case management. It is not sure in what

degree the intensive management itself is beneficial to patients. If the effectiveness of phase-specific

management can be established, this practice may be feasible in other cohorts of psychotic patients

as well.


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With reference to the consistently positive outcomes of early intervention programme, the

Hospital Authority in Hong Kong launched the Early Assessment Service for Young People with

Psychosis (EASY) programme in 2001. Prior to the EASY programme (Early intervention, EI),

general psychiatric care (Standard Care, SC) consists mainly of inpatient treatment of the first

psychotic episode, followed by relatively sparse outpatient follow-up with little psychosocial

support. The initiation of EASY service involved a number of seminars and workshops raising the

awareness of early intervention to local health professionals. There are a hotline plus online form for

self-referral. Trained health professionals will then assess and plan appropriate treatment for patients

within a short period of time. Intensive case management not only includes pharmacological

intervention, but also regular contacts with case workers, psychosocial intervention, carer support

groups, etc, not to speak of referrals to community and rehabilitation services organized by non-

governmental organizations. It is a better service in terms of means of referral, intensity of

management and the use of atypical antipsychotics.

Many of the past studies which assessed the effectiveness of early intervention programmes

are limited by small sample size(14, 15), absence of control sample(16), short follow-up period(17) and

limited outcome variables(9, 18, 19). Some of the previous historical control studies evaluating early

intervention programmes only focused on early detection(20, 21), had a control sample with far

temporal proximity(21). Majority of the findings are derived from western societies which may not fit

our cultural and geographical context.

Previous pilot study of EASY programme demonstrated that patients with shorter DUP had

better treatment adherence and quicker treatment response 1 year after first presentation(18). The

present study is to extend the pilot study and evaluate the EASY service for a period of three years

(2001-2003) by comparing with the three years of standard care service (1998-2001) just before the

launch of EASY.

Aims and Objectives

1) To compare the 3-year outcome of patients receiving the EASY service with those who

received standard care prior to the launching of the EASY service.


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2) Outcome are measured in the following domains:

a. Hospitalization

b. Relapse and symptoms

c. Functioning

d. Risk behaviours

e. Disengagement

Methods

Methodology

This study compares outcome of psychosis in the first three years in matched groups of patients

before and after implementation of an early intervention service in Hong Kong. This study thus

makes use of a historical control group. There are several potential approaches to studying the

effectiveness of early intervention programmes. A randomized control trial would involve deliberate

withholding of intervention for some identified patients and is considered unethical. The other

approaches are historical control and parallel control. Parallel control methodology involves

comparing locations with and without early intervention services. This can be considered in

populations with clear-cut geographical, service and information segregation (e.g. different cities in

Scandinavia). This design however cannot be effective for the situation in Hong Kong where it is

difficult to set rigid boundaries for service territory and impossible to limit media public education

to certain subpopulations within Hong Kong. We therefore adopt the historical control methodology

for evaluating early intervention service in Hong Kong. The limitation of this approach is a potential

cohort effect. This can be minimized by choosing samples which are in close temporal proximity (as

in the current study) as well as controlling for known potential cohort factors. The samples selected

are therefore to be matched in respect to gender, diagnosis and age.

Sample definition


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The early invention (EI) sample consists of 700 cases presented to EASY service from 2001 to 2003

who fulfilled inclusion criteria. In control sample (SC), potential patients presented with first onset

psychosis from 1998 to 2001 are identified from the psychiatric case register (PsyCIS).

Inclusion criteria

1. Using ICD-10, a longitudinal diagnosis of schizophrenia, acute and transient psychotic disorder,

schizoaffective disorder, psychosis NOS, affective disorder with psychotic features.

2. Age between 15 and 30 (The majority of cases first presented in EASY before age 25).

Exclusion criteria

1. Delusional disorder.

2. Patients with significant organic condition, drug induced psychosis or mental retardation will not

be recruited.

3. Cases who had received psychiatric treatment/consultation for more than 1 month prior to their

first presentation to public mental health service in Hong Kong.

4. For EI cases, cases who had received standard care out-patient treatment over 3 months before

referring to EASY services.

Matching between cases and control

The matching procedure is one-to-one. After identifying 700 eligible cases in the EI group, cases

from the SC pool is matched one-to-one to the EI cases is in respects of gender, diagnosis and age

(±3 years).

Data Acquisition Procedure and Analysis

After case record retrieval by the clerical officer, trained research assistants acquired the data from

medical records according to a structured format and operationalized definitions. Only data that

could be reliably extracted from the medical records were used for analysis. The three-year follow-

up period was divided into 36 epochs, each lasting one month. Unless otherwise specified, measures

were taken on each of the outcome variables for each month in the specified period. Data are

acquired in the various domains, ranging from premorbid characteristics to first presentation,


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treatment, relapse, risk behaviours and service utilization (Table 1). Validity and inter-rater

reliability statistics were obtained for major outcome variables (Table 2). Statistical Package for

Social Sciences (SPSS) version 15.0 was used for statistical analyses.

Despite the study design controlled for age, gender and diagnosis, additional covariates were

identified to be included in the analysis. Continuous dependent variables were compared by

factorial ANCOVA. F-values, p-value and effect size were reported. Effect sizes were calculated by

mean difference, standard deviation and sample size (Cohen’s d). According to Cohen’s

convention(22), a small effect size corresponds to 0.20, a medium effect size corresponds to 0.50 and

a large effect size corresponds to 0.80. Categorical dependent variables were compared by logistic

regression. Results were presented in terms of odd ratios (95% CI) and p-value. Chi-square tests and

t-tests were also used as appropriate.


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Table 1 Main variables of the study Domains Variables Remarks

Demographics • Education level is defined as years of education completed

Premorbid occupational functioning Smoking

Premorbid factors

Significant life events Mode of illness onset Presentation Duration of untreated psychosis (DUP)

Medication Symptomatic outcome • Rated by CGI Severity of

Illness(23) (Positive Symptoms, Negative Symptoms and Affective Symptoms)

Outpatient attendance In-patient duration Comorbidity

Treatment of first episode and course of illness

Relapse Occupational and social functioning status

Functioning

SOFAS(24) Self-harm, violence and forensic records

Risk behaviours

Substance abuse Social services and assistance Rehabilitation programme inputs Community visits required Contact with Accident and Emergency Department

Service utilization

Disengagement • Defined as drop out from service within three years

Validity and Reliability

One experienced clinician and two trained research assistants completed 12 cases (7 EI and 5 SC)

by a tailor-made data entry form (Microsoft Office Access) used in actual data collection. Major

variables, like DUP, functioning, SOFAS, hospitalization days were selected for validity and inter-

rater reliability testing. Validity tests compared the ratings between clinician and research assistant.

The ICC and weighted Kappa scores (Table 2) of validity test represented that ratings from research

assistants were comparable to ratings from clinician (assuming clinical evaluation is the gold

standard in our outcome measures). Inter-rater reliability tests compared ratings between two

research assistants. The generated scores represented a satisfactory level of concordance on the

ratings between research assistants. Besides the validity and reliability testing, there were weekly


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consensus meetings among clinician and research assistants during the period of data collection, so

as to minimize bias and errors.

Table 2 Validity and inter-rater reliability tests for major variables ICC Weighted Kappa Validity Inter-rater Reliability Validity Inter-rater Reliability DUP 0.777 0.702 --- --- Functioning scorea 0.832 0.978 --- --- SOFASb 0.905 0.865 --- --- Hospitalization daysc 0.998 0.999 --- --- Type of Antipsychoticsd --- --- 0.851 0.939 a Mean ICC of mean score of each year (3 years in total). b Mean ICC of SOFAS score of each month (36 months in total). c ICC of total hospitalization days. d Mean of 36-month weighted Kappa. Results

Demographics

By design, the samples were matched for gender, diagnosis, and age (Table 3 and 4). Importantly,

the two samples also match for premorbid occupational functioning (Table 3). The EI group had a

slightly higher number of years of education (EI: 10.90 years [±2.33]; SC: 10.55 years [±2.40]; p =

0.01). The actual difference is small (0.35 years). The EI group also had fewer subjects with a

history of immigration (EI = 20.1%; SC = 28.7%). The difference in immigration history is likely

to be due to fewer non-Chinese speaking patients presenting to the EASY service, presumably as a

result of most media work being conducted in Chinese.

Table 3 Demographics of patients in EI an SC

Age (years) Education (years)

Gender Immigration history

Premorbid occupational impairmenta

Mean (SD) M/F HK/China/Others Impaired EI 21.12 (3.41) 10.90 (2.33)** 359/341 559/126/15*** 49 SC 21.27 (3.44) 10.55 (2.40) 359/341 499/146/55 49 ** p < 0.01. *** p < 0.001. a Impairment means unemployment and prolonged educational stagnation. Table 4 Diagnosis of patients in EI and SC Schizophrenia

and schizoaffective disorder

Acute and Transient Psychotic Disorder

Psychosis NOS BAD with psychotic symptoms

Depressive episode with psychotic symptoms

EI 484 87 46 54 29SC 486 87 44 54 29


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Note: There’s no significant difference between EI and SC. Duration of untreated psychosis (DUP)

The duration of DUP was highly similar in both groups (Table 5). Although the EASY programme

in Hong Kong aims to shorten the DUP of patients, the overall DUP was not significantly different

between the EI and the SC groups. This could be due to several reasons: the two comparison groups

might be too close in time for the public media campaign associated with the EASY programme to

make an impact on the help seeking behaviour of the general public. It is also conceivable that at the

launch of the EASY programme some patients with previously long DUP may be taken up by the

EASY programme because of the improved access to care. This explanation was compatible with

the onset mode statistics. There were significantly more patients with gradual onset in EI than SC.

There was no difference between EI and SC groups for life events, smoking and substance abuse. It

is noted that the prevalence of smoking in both patient samples were higher than the general

population (age/gender corrected)1.

Years of education and mode of onset, which were not controlled by design, showed

significant difference between EI and SC. Continuous dependent variables were compared by

factorial ANCOVA with type of intervention (EI / SC) and mode of onset as factors, and years of

education as covariates (unless otherwise specified). Categorical dependent variables were

compared by logistic regression with type of intervention (EI / SC), mode of onset and years of

education as covariates.

Table 5 Subjects’ Characteristics in DUP EI SC χ2 / t P DUP (days) 241.49 (±374.06) 241.31 (470.65) t = .01 0.994 Smokers (current smokers only)a 179 (25.6%) 185 (26.4%) χ2 = .15 0.701 15-19 42 (16.3%) 53 (23.2%) χ2 = 3.66 0.056 20-29 136 (30.8%) 132 (28.1%) χ2 = .72 0.396 Male 132 (36.8%) 122 (34.0%) χ2 = .42 0.520 Female 47 (13.8%) 63 (18.5%) χ2 = 2.56 0.109 Onset mode (Acute/Sub-acute/Gradual) 166/50/484 229/48/422 χ2 = 14.33 0.001

1 In 2000, the prevalence of current daily cigarette smokers was 4.5% in age group 15-19 and 12.1% in age group 20-29. The prevalence of daily cigarette smoker was 22% for male and 3.5% for female. Source: Tobacco Control Office http://www.tco.gov.hk/english/infostation/infostation_sta_01.html


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a Only patients who were smokers before the first presentation to mental health service were counted. Pharmacotherapy

There was significantly more EI patients taking atypical antipsychotics than SC patients at any

time-point, with p-value <.001 (chi-square tests). In the first three months, many EI patients had

already shifted from conventional to atypical medication. In the first month, 152 EI patients

already started using atypical antipsychotics but only 41 SC patients started at the same month.

At the end of three years, 274 EI patients were on atypical antipsychotics compared to 126 SC

patients. EI patients took significantly longer period of atypical antipsychotics, and shorter

period of conventional antipsychotics (Figures 1a and 1b). More SC patients dropped out from

follow up (F = 20.96, p < 0.001, effect size = -0.28).

Figures 1a & 1b Use of Antipsychotics in 36 months

Note: Planned discontinuation means the stop of medication is agreed by clinician, no matter the plan

of discontinuation is patient- or clinician-initiated. Both antipsychotics means the patients is taking both conventional and atypical antipsychotics at the same time. Irregular attendance means absence of medications due to default in out-patient follow-up. Statistical tests: 1) Planned discontinuation: F = 3.47, p = 0.063. 2) Atypical antipsychotics: F = 88.11, p < 0.001, effect size = 0.74.

EIUse of Antipsychotics

0

100

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400

500

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700

1 4 7 10 13 16 19 22 25 28 31 34

Time

No.

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Planned discontinuation Conventional antipsychoticsAtypical antipsychotics Both antipsychoticsIrregular attendance Drop out from service

SCUse of Antipsychotics

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1 4 7 10 13 16 19 22 25 28 31 34

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Planned discontinuation Conventional antipsychotics

Atypical antipsychotics Both antipsychoticsIrregular attendance Drop out from service


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3) Conventional antipsychotics: F = 26.43, p < 0.001, effect size = -0.49. 4) Both antipsychotics: F = 2.81, p = 0.094. 5) Irregular attendance: F = 0.10, p = 0.758. 6) Drop out from service: F = 20.96, p < 0.001, effect size = -0.28.

Outcome 1: Hospitalization

In the first month of treatment, 634 (90.6%) patients out of 700 from SC had been hospitalized,

compared to 328 (46.9%) patients from EI. Significantly fewer EI patients were hospitalized, with

odd ratios of 0.09 (95% CI 0.069-0.125, p < 0.001). A significant main effect was obtained for

type of intervention on the total duration of hospitalization (F = 19.74, p < 0.001, effect size = -

0.43). EI group had significantly shorter duration of hospitalization than SC group (EI: M =

61.05, ± 105.77; SC: M = 114.70, ± 142.27). EI group also had significantly fewer number of

admission than SC group (EI: M = 1.03, ± 1.12; SC: M = 1.78, ± 1.27) (F = 46.43, p < 0.001,

effect size = -0.63).

To examine the effect of atypical antipsychotics on reduced hospitalization, patients were

grouped into “atypical antipsychotics group” (AA) if they took atypical medications for 265 days

(mean) or more, or “conventional antipsychotics group” (CA) if less than 265 days. Patient who

had atypical antipsychotics actually had significantly longer duration of hospitalization

(ANCOVA with medication, type of intervention and mode of onset as factors and years of

education as covariate, F = 12.12, p =0.001). This may have to do with the fact that atypical

antipsychotics are often used when the response and side effect profiles to conventional

antipsychotics are unsatisfactory.

Outcome 2: Relapses and Symptoms

Overall there is no difference in relapse rate between EI and SC patients. In the first year, 124

(17.7%) EI patients and 147 (21%) SC patients relapsed. For those who did not relapse in the

first year and kept attending the clinic in the second year (EI:n = 519; SC: n = 430), 149 (28.7%)

EI patients and 116 (27.0%) SC patients relapsed. And for those who did not relapse in the first

two years and kept attending the clinic in the third year (EI: n = 343; SC: n = 282), 71 (20.7%)

EI patients and 67 (23.8%) SC patients relapsed. In terms of number of relapse episodes, there


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was also no significant difference between EI and SC. We tried to group the patients with 4 or

more episodes into one group (EI, n = 26; SC, n = 48) and the patients with 1 to 3 episodes into

another group (EI, n = 674, SC, n = 652), there were fewer people with multiple episodes in EI

group, with odds ratio of 0.53 (95% CI 0.320 – 0.858, p = 0.01).

To evaluate the symptomatic outcomes between groups, a score was generated by

averaging individual’s monthly positive and negative symptom scores respectively. The mean

positive and negative symptom scores were 1.63 (±0.63) and 1.47 (±0.54) in EI respectively.

Respective statistics in SC were 1.73 (±0.91) and 1.56 (±0.69). There was main effect for the

type of intervention on positive symptom score (F = 8.47, p = 0.004, effect size = -0.13). And

there was main effect for type of intervention on negative symptom score (F = 5.73, p = 0.017,

effect size = -0.15). The effects sizes of symptomatic outcomes were small. Interpretations on the

positive findings should be cautious because of limited sensitivity in the use of medical records

review to estimate symptom levels.

Figure 2 Relapse Timeline Note: Patients will not be counted as “dropped out” if they had at least one month of follow-up in that year. Outcome 3: Functioning

Relapsed (n=124)

Not Relapsed (n=576)

Dropped out (n=57)


Relapsed (n=149)

Dropped out (n=27)


Relapsed (n=71)

Relapsed (n=147)


Dropped out (n=123)


Relapsed (n=116)

Dropped out (n=32)


Relapsed (n=67)

Year 1 Year 2 Year 3 Year 1 Year 2 Year 3

EI SC


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Across 36 months, more EI patients engaged in full-time and part-time employment than SC

patients (Figure 3a & 3b). The difference was particularly remarkable in the early course of

treatment. (We hypothesize this may be a result of occupational disruption following a period of

hospitalization).

Figures 3a & 3b Occupational Functioning in 36 Months

Note: The decreasing slope represents the patients disengaged from the mental health services.

We quantified functioning data as follows: Patients gained 1 mark for each month of full-

time employment and 0.5 marks for each month of part-time employment. For all other

categories, no mark would be given. So, the sum of scores could be from 0 to 36. An average

score was then calculated for comparison.

Occupational Functioning in 36 Months (SC)

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1 4 7 10 13 16 19 22 25 28 31 34

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In-patient Rehab Unemployed Part time Full time Missing

Occupational Functioning in 36 Months (EI)

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700

1 4 7 10 13 16 19 22 25 28 31 34

Time

No. o

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In-patient Rehab Unemployed Part time Full time Missing


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Figure 4 Occupational Functioning Score

Note: M1-M2, p < 0.001. M3, 7-8, 12-16, 20, 22, 24, 29-34, p < 0.01. M4, 6, 9, 11, 17-19, 21, 23, 27-28, 36, p < 0.05.

From the above results, it is not clear the whether the improved functioning is due to the

intervention itself or other factors, like atypical antipsychotics. Again, we divided the patients

into “atypical antipsychotics group” (AG) and “conventional antipsychotics group” (CG) and

explored their relationship with the functioning score. AG and CG had no difference in

functioning scores in either group (t-tests).

The factorial ANCOVA (type of intervention, mode of onset and medication as factors

and years of education as covariates) only reflected the main effect on the type of intervention on

functioning score (F = 13.54, p < 0.001, effect size = 0.41). EI patients (M = 0.53, ±0.34) had

significantly higher functioning score than SC patients (M = 0.38, ±0.38). However, no main

effect could be obtained for medication (F =1.55, p =0.214). And there was no significant result

in the Intervention x Medication interaction for functioning score. Monthly comparisons of

functioning scores were all significantly different in 36 time-points except in month 5, 10, 25, 26

and 35 (Figure 4 and Appendix A).

Social and Occupational Functioning Assessment Scale (SOFAS) (24) was another

assessment tool to evaluate the social and occupational functioning of the patients. The three-

Occupational Functioning Score

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35

Time

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5 m

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for

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EISC


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year SOFAS score was highly correlated with the three-year functioning score, r = .81, p < .001.

EI had a mean SOFAS score of 61.15 (± 10.18) whilst SC is 54.63 (±10.62) (F = 58.11, p <

0.001, effect size = 0.60). If we analyzed the SOFAS scores by year, EI patients had higher

SOFAS scores in the first year (F = 58.86, p < 0.001, effect size = 0.68), second year (F = 51.76,

p < 0.001, effect size = 0.51), and the third year (F = 34.35, p = 0.001, effect size = 0.45). Both

the functioning score and SOFAS reflected that patients from EI successful achieved higher level

of functioning in three years.

Outcome 4: Risk Behaviours

Risk behaviours, including suicide attempt, deliberate self harm (no intention to die), violence,

forensic records and substance abuse, were captured from the medical records. Behaviours were

recorded by episodes. More people in the SC group had records of suicide attempts, deliberate

self harm and violence in the three years (Table 6). Although there was no difference in the

number of people who had attempted substance abuse, the duration of substance abuse (n=96)

was evidently to be significantly longer in SC group (F = 3.95, p = 0.05, effect size = -0.52). 8

people from EI were deceased in three years, compared to 22 people from SC. However, only 7

out of 8 in EI and 18 out of 22 in SC were confirmed to be completed suicide. By just comparing

the completed suicide rate, SC had significantly more suicides.

Table 6 Logistic regression with the targeted event (the first column) as dependent variable, type of intervention, years of education and mode of onset as independent variables.

No. of subjects with positive record EI SCa Exp(B)b p OR (95% CI)

Suicide attempt 90 139 0.604 0.001 0.451 - 0.809 Completed suicide 7 18 0.376 0.032 0.154 - 0.919 Deliberate self harm 56 81 0.690 0.045 0.480 - 0.992 Violence 87 143 0.573 0.000 0.426 - 0.770 Forensic Record 23 20 1.216 0.535 0.656 – 2.252 Substance abuse 40 56 0.803 0.327 0.518 – 1.244 a Reference group. b Adjusted odd ratios. Outcome 5: Disengagement

Disengagement here is defined that the case is closed within three years of treatment and not re-

activated in that period. On average, EI patients stayed in the mental health system for 31.82


21

(±9.32) months whereas SC patients stayed for 28.66 (±12.70) months (F = 20.96, p < 0.001,

effect size = 0.28). 510 (72.9%) EI patients and 460 (65.7%) SC patients kept attending the

clinics for three years EI group had 23% reduction in the odds of disengaging from the service

(95% CI 0.605 – 0.966, p = 0.025).

DUP and major outcomes

There was no significant difference in DUP between two groups (t-test) (Table 5). Interestingly,

DUP was negatively correlated with total hospitalization days in EI, rs = -0.18, p < 0.01. On the

contrary, DUP was positively correlated with total hospitalization days in SC, rs = 0.16, p < 0.01.

The contradicting results required further exploration. In respect of functioning, DUP was

negatively correlated with overall functioning score, rs = -0.10, p < 0.01, and SOFAS in SC, rs =

-0.08, p < 0.05. No similar trend could be found in EI group (Appendix B1 & B2). For other

outcome variables, the group with longer DUP (> 71.5 days) had more violent acts but fewer

cases of disengagement in SC. In the EI group, longer DUP was associated with substance abuse

only (Table 7).

Table 7 Chi-square tests of DUP with other major outcome variables

No. of patients with positive records EI SC

S. DUP (n=310)

L.DUP (n=390) χ2 p

S. DUP (n=389)

L. DUP (n=311) χ2 p

Suicidal attempt 45 45 1.37 0.242 69 70 2.47 0.116 Delibrate self harm 23 33 0.26 0.614 45 36 0.00 0.998 Violence 34 53 1.09 0.296 65 78 7.45 0.006 Forensic Record 8 15 0.87 0.351 9 11 0.93 0.334 >1 episode 163 181 2.63 0.105 175 155 1.63 0.201 Substance abuse 10 30 6.40 0.011 31 25 0.00 0.973 Disengagement 81 109 0.29 0.591 151 89 7.98 0.005 Note: S. DUP = Short DUP (<= 71.5 days); L. DUP = Long DUP (> 71.5 days) Discussion

EI patients had higher functioning score over 36 months. For enduring disorders like psychotic

disorders, functional outcome constitute one of the most important measures of long term

outcome and impact of the disorder on individuals and society. Particularly important is the

observation that for patients with comparable premorbid levels of functioning, the EI group did


22

substantially better 3 years after the first psychotic episode. Different aspects of the EI

intervention may contribute to the difference: firstly a number of SC patients lost their jobs in

their first presentation to the psychiatric service as an in-patient; secondly superiority may also

be attributed to the intensive case management by the multidisciplinary team, which has more

capacity to tackle negative symptoms and motivational problems often encountered by patients

with psychosis. Atypical antipsychotics appeared to have no effect on functioning.

EI also successfully reduced the length of hospitalization. It is likely that this was

achieved through the intensive EASY out-patient and community based service. The data from

EASY suggest that some hospitalization for managing early psychosis might be unnecessary and

could be replaced by intensive out-patient monitoring. Not only did unnecessary hospitalization

affect patients’ daily living, it also created burden to the mental health system, and may impede

rehabilitation. However, it is important to recognize that inpatient treatment is still need for some

cases even for the EASY service.

EI also successfully reduced suicide rate and self harm behaviour among this cohort of

patients. Psychosis is an important cause of suicide, with most of the suicides taking place early

in the course of the illness. Better care in the initial years of psychosis may be of strategic

importance in improving suicide related outcomes in psychosis.

There was no difference in relapse rate between the two groups, suggesting that the form

of intervention employed by EI did not reduce relapse. Since one of the strongest predictors for

relapse is medication adherence. It is understandable that after a single episode of illness, many

patients would opt for medication discontinuation after a period of clinical stability. Since

evidence based information regarding relapse rate in this stage is scarce, many clinicians would

support patients in a cautious withdrawal from maintenance treatment, following a number of

clinical practice guidelines. It is likely that for the EASY patients, relapses tended to be detected

early and in many cases managed without hospitalization. Significantly fewer EI patients

disengaging from the service may be attributable to intensive case management, and may allow

case workers to have a longer period of close monitoring.


23

One of the aims of early intervention programmes is to promote early detection and early

treatment for case (i.e. to shorten the DUP), Data from this study show that in the initial years of

the implementation of an early intervention programme, there has not yet been an impact in the

DUP. Factors contributing to DUP are highly complex some will take a longer period of time to

show an impact. The current findings of an improved outcome before there is any change in

DUP suggest that the interventional component of the EASY programme is effective in its own

right. The changes in outcome produced are not mediated by shortening of DUP.

Limitations

This study aims to provide a territory-wide well matched, representative sample. As our key data

source relied on medical records. There is an inherent limitation to the observations which can be

reliably obtained (e.g. quality of life, indirect impact to family). As the study had focused on

clinical outcomes, a broader consideration of costs would allow a full cost-effective comparison.

The historical control study designed is constrained by the territory-wide nature of the EASY

programme which ruled out a randomized control study.

Implications

Since the launching of the early intervention of psychosis programme in Hong Kong in 2001, the

current study (2005-2007) provided a timely evaluation of the 3-year outcome of the programme.

We have found that the service has been effective in improving outcome for a well-matched

clinical population in a number of domains. Although this study was not planned to be a full

scale health economics study, some of the indicators suggest that there may be cost-saving

features for the health care system and the society (e.g. reduced hospitalization, lower self-harm

and violent behavoiur, improved occupational functioning). It may be an important next step to

conduct a full health economic study of the cost effectiveness of the EASY programme. The

EASY programme provides service for patients up to age 25. In the future development of

service for those above 25, there may be opportunity for planning a randomized controlled study

to further strengthen the conclusions. A further study on DUP with a cohort incepted several

years later may also shed more light on the impact on the DUP. Furthermore, there is a need to


24

study the efficacy of individual interventional components within the EASY programme in order

to identify processes of key impact. The study also points toward the need for more information

about relapse risk and improved maintenance therapy. Finally this study only captured the 3-year

outcome. Arguably a longer term outcome study e.g. 5-years may be important to demonstrate

the sustainability of the advantages gained in the initial years.

Dissemination

Results have been disseminated in the Health Research Symposium 2007 on 29th September,

2007.

This final report is useful to all service workers and health professionals within the public

psychiatric services and NGOs which have frequent contact with patients with psychotic

disorders, e.g., sheltered workshop and half-way house.

Publications

No paper has been published yet.


25

Bibliography 1. Rossler W, Salize HJ, van Os J, Riecher-Rossler A. Size of burden of schizophrenia and psychotic disorders. European Neuropsychopharmacology Special Issue: Size and Burden of Mental Disorders in Europe. 2005 Aug 2005;15(4):399-409. 2. Birchwood MJ, Fowler DR, Jackson C. Early intervention in psychosis : a guide to concepts, evidence, and interventions. Chichester, England: Wiley; 2000. 3. McGorry PD, Edwards J, Mihalopoulos C, Harrigan SM, et al. EPPIC: An evolving system of early detection and optimal management. Schizophrenia Bulletin. 1996 1996;22(2):305-26. 4. Szymanski SR, Cannon TD, Gallacher F, Erwin RJ, Gur RE. Course of treatment response in first-episode and chronic schizophrenia. American Journal of Psychiatry. 1996 Apr;153(4):519-25. 5. McEvoy JP, Schooler NR, Wilson WH. Predictors of therapeutic response to haloperidol in acute schizophrenia. Psychopharmacology Bulletin. 1991 1991;27(2):97-101. 6. Harris MG, Henry LP, Harrigan SM, Purcell R, Schwartz OS, Farrelly SE, et al. The relationship between duration of untreated psychosis and outcome: An eight-year prospective study. Schizophrenia Research. 2005 Nov 2005;79(1):85-93. 7. Killackey Ei, Yung AR. Effectiveness of early intervention in psychosis. Current Opinion in Psychiatry. 2007 Mar 2007;20(2):121-5. 8. Melle I, Johannesen JO, Friis S, Haahr U, Joa I, Larsen TK, et al. Early Detection of the First Episode of Schizophrenia and Suicidal Behavior. American Journal of Psychiatry. 2006 May 2006;163(5):800-4. 9. Clarke M, Whitty P, Browne S, McTigue O, Kamali M, Gervin M, et al. Untreated illness and outcome of psychosis. British Journal of Psychiatry. 2006 Sep 2006;189(3):235-40. 10. Norman RMG, Malla AK. Duration of untreated psychosis: A critical examination of the concept and its importance. Psychological Medicine. 2001 Apr 2001;31(3):381-400. 11. Norman RMG, Lewis SnW, Marshall M. Duration of untreated psychosis and its relationship to clinical outcome. British Journal of Psychiatry Special Issue: Early psychosis: A bridge to the future. 2005 Aug 2005;187(Suppl48):s19-s23. 12. Verdoux Hln, Cougnard A. The early detection and treatment controversy in schizophrenia research. Current Opinion in Psychiatry. 2003 Mar 2003;16(2):175-9. 13. Edwards J, McGorry PD. Key service elements - (b) initial assessment and treatment. Implementing early intervention in psychosis : a guide to establishing early psychosis services. London: Martin Dunitz; 2002. p. xv, 186. 14. Larsen TK, McGlashan TH, Johannessen JO, Friis S, Guldberg C, Haahr U, et al. Shortened duration of untreated first episode of psychosis: Changes in patient characteristics at treatment. American Journal of Psychiatry. 2001 Nov 2001;158(11):1917-9. 15. Kuipers E, Holloway F, Rabe-Hesketh S, Tennakoon L. An RCT of early intervention in psychosis: Croydon Outreach and Assertive Support Team (COAST). Social Psychiatry and Psychiatric Epidemiology. 2004 May 2004;39(5):358-63. 16. Addington J, Leriger E, Addington D. Symptom Outcome 1 Year After Admission to an Early Psychosis Program. The Canadian Journal of Psychiatry / La Revue canadienne de psychiatrie Special Issue: Transcultural psychiatry. 2003 Apr 2003;48(3):204-7. 17. Melle I, Larsen TK, Haahr U, Friis S, Johannessen JO, Opjordsmoen S, et al. Reducing the duration of untreated first-episode psychosis: Effects on clinical presentation. Archives of General Psychiatry. 2004 Feb 2004;61(2):143-50. 18. Chow DHF, Law BTT, Chang E, Chan RCK, Law CW, Chen EYH. Duration of untreated psychosis and clinical outcome 1 year after first-episode psychosis. Hong Kong Journal of Psychiatry. 2005 Mar 2005;15(1):4-8. 19. Malla A, Schmitz N, Norman R, Archie S, Windell D, Roy P, et al. A multisite Canadian study of outcome of first-episode psychosis treated in publicly funded early intervention services. The Canadian Journal of Psychiatry / La Revue canadienne de psychiatrie. 2007 Sep 2007;52(9):563-71. 20. Malla A, Norman R, Scholten D, Manchanda R, McLean T. A community intervention for early identification of First Episode Psychosis: Impact on duration of untreated psychosis (DUP) and patient characteristics. Social Psychiatry and Psychiatric Epidemiology. 2005 May 2005;40(5):337-44. 21. Johannessen JO, McGlashan TH, Larsen TK, Horneland M, Joa I, Mardal S, et al. Early detection strategies for untreated first-episode psychosis. Schizophrenia Research Special Issue: Ethics of early treatment intervention in schizophrenia. 2001 Aug 2001;51(1):39-46.


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22. Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale, N.J.: L. Erlbaum Associates; 1988. 23. Guy W. Clinical global impression. ECDEU Assessment Manual for Psychopharmacology (revised). Rockville, MD: National Institute of Mental Health 1976. p. 217-21. 24. American Psychiatric Association., American Psychiatric Association. Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders : DSM-IV-TR. 4th ed. Washington, D.C.: American Psychiatric Association; 2000.


27

List of Research Workers

Principal Investigator: Dr. Eric YH Chen (陳友凱醫生)

Co-investigators: Dr. Kathy Chan (陳葆雯醫生)

Dr. Cindy PY Chiu (趙珮瑜醫生)

Dr. Dicky Chung (鍾維壽醫生)

Dr. Eva Dunn (鄧麗華醫生)

Dr. Se Fong Hung (熊思方醫生)

Dr. May Lam (林美玲醫生)

Dr. Chi Wing Law (羅志榮醫生)

Ms Margaret Tay (鄭淑梅女士)

Dr. Steve Tso (左思賦醫生)

Dr. Ka Chee Yip (葉嘉池醫生)

Dr. Gar Chung Yiu (姚家聰醫生)

Coordinators: Miss Christy LM Hui (許麗明小姐)

Miss Jennifer YM Tang (鄧綺汶小姐)

Miss Gloria HY Wong (黃凱茵小姐)

Research Assistants: Miss Carol Yew (姚穎詩小姐)

Miss Joanna Wong

Miss Cecilia AuYeung

Miss Jennifer YM Tang (鄧綺汶小姐)


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Financial Statement

The study is fully funded by Health and Health Services Research Fund, Food and Health Bureau,

Hong Kong Special Administration Region. The reference number is 03040141.


29

Appendices

Appendix A Comparison of functioning scores in 36 months

n Mean (SD) Month EI SC EI SC F p M1 698 689 0.30 (0.45) 0.07 (0.26) 29.79 <0.001M2 689 640 0.35 (0.46) 0.17 (0.37) 19.13 <0.001M3 680 622 0.40 (0.47) 0.25 (0.42) 9.98 0.002M4 673 611 0.44 (0.48) 0.32 (0.45) 4.64 0.031M5 664 605 0.46 (0.48) 0.35 (0.46) 1.43 0.232M6 661 595 0.47 (0.48) 0.37 (0.47) 4.00 0.046M7 656 589 0.49 (0.47) 0.38 (0.47) 6.82 0.009M8 653 578 0.50 (0.47) 0.39 (0.47) 7.24 0.007M9 648 576 0.50 (0.47) 0.42 (0.48) 3.93 0.048M10 645 571 0.51 (0.47) 0.43 (0.48) 3.25 0.072M11 643 567 0.54 (0.47) 0.43 (0.48) 6.32 0.012M12 639 561 0.55 (0.47) 0.42 (0.48) 8.06 0.005M13 637 558 0.56 (0.47) 0.44 (0.48) 8.99 0.003M14 633 552 0.56 (0.47) 0.45 (0.48) 8.21 0.004M15 629 552 0.57 (0.47) 0.44 (0.48) 11.04 0.001M16 625 549 0.58 (0.46) 0.44 (0.48) 7.37 0.007M17 662 543 0.57 (0.46) 0.45 (0.48) 5.64 0.018M18 620 543 0.57 (0.46) 0.46 (0.48) 6.59 0.010M19 617 537 0.56 (0.46) 0.46 (0.48) 6.42 0.011M20 614 535 0.57 (0.47) 0.46 (0.48) 6.76 0.009M21 610 531 0.55 (0.47) 0.46 (0.47) 6.34 0.012M22 607 529 0.55 (0.47) 0.45 (0.48) 7.21 0.007M23 603 527 0.56 (0.47) 0.44 (0.48) 6.73 0.010M24 602 520 0.57 (0.47) 0.45 (0.48) 9.70 0.002M25 599 518 0.55 (0.47) 0.47 (0.48) 2.23 0.136M26 585 515 0.57 (0.47) 0.47 (0.48) 2.73 0.099M27 581 513 0.58 (0.47) 0.47 (0.47) 6.41 0.012M28 575 512 0.57 (0.47) 0.46 (0.47) 4.06 0.044M29 571 511 0.57 (0.46) 0.44 (0.47) 9.45 0.002M30 563 509 0.57 (0.47) 0.45 (0.47) 6.96 0.008M31 560 505 0.59 (0.46) 0.45 (0.47) 10.12 0.002M32 555 499 0.59 (0.47) 0.45 (0.47) 11.61 0.001M33 551 494 0.58 (0.47) 0.45 (0.47) 9.54 0.002M34 548 492 0.58 (0.47) 0.45 (0.47) 8.37 0.004M35 545 490 0.58 (0.47) 0.46 (0.47) 3.64 0.057M36 536 485 0.57 (0.47) 0.46 (0.47) 4.51 0.034


30

Appendix B1 DUP and major outcome correlates in EI

Appendix B2 DUP and major outcome correlates in SC Variable 1. 2. 2a. 2b. 2c. 3. 3a. 3b. 3c. 4. 4a. 4b. 4c. 5. 6. 7.

1. DUP (days) ― 2. Hospitalization days .16** ―

2a. Y1 hospitalization days .11** .84** ― 2b. Y2 hospitalization days -.00 .41** .05 ― 2c. Y3 hospitalization days 00 .46** .10* .19** ― 3. Functioning score -.10** -.16** -.11** -.20** -.22** ―

3a. Y1 Functioning score -.09* -.23** -.24** -.07 -.07 .83** ― 3b. Y2 Functioning score -.17** -.28** -.18** -.25** -.13** .91** .63** ― 3c. Y3 Functioning score -.12** -.26** -.08 -.18** -.34** .84** .40** .69** ― 4. SOFAS -.08* -.16** -.09* -.32** -.34** .86** .68** .81** .76** ―

4a. Y1 SOFAS -.07 -.27** -.32** -.11** -.13** .71** .83** .53** .33** .80** ― 4b. Y2 SOFAS -.17** -.36** -.19** -.42** -.21** .83** .53** .88** .64** .91** .56** ― 4c. Y3 SOFAS -.15** -.34** -.10* -.26** -.48** .74** .36** .61** .87** .86** .38** .70** ― 5. CGI Positive .03 -.01 -.07 .28** .34** -.37** -.24** -.26** -.31** -.53** -.38** -.35** -.39** ― 6. CGI Negative .16** .25** .18** .19** .21** -.37** -.30** -.39** -.41** -.42** -.34** -.46** -.46** .29** ― 7. CGI Affective -.05 .29** .19** .34** .24** -.060 -.05 -.11** -.14** -.14** -.13** -.19** -.21** .18** .09* ―

Variable 1. 2. 2a. 2b. 2c. 3. 3a. 3b. 3c. 4. 4a. 4b. 4c. 5. 6. 7. 1. DUP (days) ― 2. Hospitalization days -.18** ―

2a. Y1 hospitalization days -.22** .87** ― 2b. Y2 hospitalization days -.05 .40** .08* ― 2c. Y3 hospitalization days -.03 .39** .14** .10* ― 3. Functioning score -.07 -.32** -.24** -.22** -.14** ―

3a. Y1 Functioning score -.00 -.34** -.35** -.06 -.07 .84** ― 3b. Y2 Functioning score -.13** -.23** -.12** -.24** -.08* .90** .62** ― 3c. Y3 Functioning score -.14** -.26** -.10* -.25** -.21** .84** .47** .71** ― 4. SOFAS -.05 -.27** -.17** -.29** -.17** .79** .65** .72** .68** ―

4a. Y1 SOFAS -.03 -.38** -.40** -.10* -.04 .69** .80** .52** .39** .80** ― 4b. Y2 SOFAS -.09* -.20** -.06 -.34** -.07 .71** .51** .77** .56** .91** .63** ― 4c. Y3 SOFAS -.12** -.21** -.03 -.27** -.28** .69** .43** .58** .78** .86** .48** .72** ― 5. CGI Positive .20** -.03 -.13** .20** .14** -.23** -.12** -.27** -.26** -.33** -.19** -.34** -.30** ― 6. CGI Negative .13** .22** .15** .16** .10* -.34** -.30** -.31** -.32** -.43** -.39** -.41** -.42** .20** ― 7. CGI Affective -.03 .09* .05 .14** .13** -.09* -.04 -.09* -.10* -.17** -.11** -.16** -.17** .25** .13** ―