First-episode psychosis integrative treatment: Estonian experience

Abstract

Purpose
Research on first-episode psychosis early intervention has shown significant positive effects on psychopathological, functional and quality-of-life outcome measures. The effects reported have however been short-term and there is still only limited information about the long-term effects. This article will present the short-term results of an effectiveness study in a Baltic country and the first results of a registry-based long-term follow-up.

Methods
One hundred and ninety-nine first-episode psychosis patients were included in the early intervention effectiveness study in 2004–2008, and 107 were available for a follow-up after two years. Registry-based ten-year follow-up (n = 116) was conducted with a retrospectively formed control group (n = 114).

Results
Patients who received early intervention had substantial symptomatic improvement (BPRS score reduction > 50%) after 6 months of treatment, the Global Assessment of Functioning (GAF) scores were significantly improved after 6 months, and the quality of life after 12 months was significantly higher than at the beginning of treatment. After 2 years employment increased by 14% (43.9–57.9%). Long-term follow-up revealed that significantly fewer patients in the intervention group had been in supported housing compared to the control group. Patients in the intervention group had spent more time working during the follow-up period and had almost two times larger incomes, suggestive of higher employment/salary level.

Conclusions
Early intervention with flexible duration has positive long-term effects on the functioning of patients.

Full text

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First-episode psychosis integrative treatment:
Estonian experience
Karola Peebo, Erika Saluveer, Harri Küünarpuu, Teele Orgse & Jaanus Harro
To cite this article: Karola Peebo, Erika Saluveer, Harri Küünarpuu, Teele Orgse & Jaanus Harro
(2021): First-episode psychosis integrative treatment: Estonian experience, Nordic Journal of
Psychiatry, DOI: 10.1080/08039488.2021.1946139
To link to this article: https://doi.org/10.1080/08039488.2021.1946139
Published online: 18 Jul 2021.
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ARTICLE
First-episode psychosis integrative treatment: Estonian experience
Karola Peebo
a,b
, Erika Saluveer
a
, Harri K€
u€
unarpuu
a
, Teele Orgse
a
and Jaanus Harro
a,b,c
a
North Estonia Medical Centre, Psychiatry Clinic, Tallinn, Estonia;
b
School of Natural Sciences and Health, Tallinn University, Tallinn, Estonia;
c
Chair of Neuropsychopharmacology, Institute of Chemistry, Faculty of Science and Technology, University of Tartu, Tartumaa, Estonia
ABSTRACT
Purpose: Research on first-episode psychosis early intervention has shown significant positive effects
on psychopathological, functional and quality-of-life outcome measures. The effects reported have
however been short-term and there is still only limited information about the long-term effects. This
article will present the short-term results of an effectiveness study in a Baltic country and the first
results of a registry-based long-term follow-up.
Methods: One hundred and ninety-nine first-episode psychosis patients were included in the early
intervention effectiveness study in 2004–2008, and 107 were available for a follow-up after two years.
Registry-based ten-year follow-up (n¼116) was conducted with a retrospectively formed control
group (n¼114).
Results: Patients who received early intervention had substantial symptomatic improvement (BPRS
score reduction >50%) after 6months of treatment, the Global Assessment of Functioning (GAF)
scores were significantly improved after 6 months, and the quality of life after 12 months was signifi-
cantly higher than at the beginning of treatment. After 2 years employment increased by 14%
(43.9–57.9%). Long-term follow-up revealed that significantly fewer patients in the intervention group
had been in supported housing compared to the control group. Patients in the intervention group
had spent more time working during the follow-up period and had almost two times larger incomes,
suggestive of higher employment/salary level.
Conclusions: Early intervention with flexible duration has positive long-term effects on the functioning
of patients.
ARTICLE HISTORY
Received 30 December 2020
Revised 10 June 2021
Accepted 15 June 2021
KEYWORDS
First-episode psychosis;
early intervention; long-
term outcomes
Background
Until almost three decades ago interventions in psychotic
disorders were similar in all phases of the disease, offering
the same treatment approach to first-episode and chronic
patients alike [1]. Over the last 20 years, a reform in first-epi-
sode psychosis treatment has taken place. The first few years
after psychosis onset are considered the critical period, and
intensive intervention in this period can affect the long-term
course of the disease [2]. Based on these principles the early
intervention in psychosis paradigm was established in
Australia in the early 1990s [3], that soon after spread all
over the world.
A meta-analysis including 10 randomized controlled trials
demonstrated better symptomatic and functional outcomes
for early intervention services compared to treatment as
usual [4]. The largest randomized controlled trial in early
intervention was conducted in Denmark (the OPUS trial). The
trial compared integrated multi-disciplinary team-based treat-
ment to standard community treatment and showed better
clinical and functional outcomes for the integrated treatment
group [5]. They also carried out long-term follow-ups, and
found that the short-term gains were mostly lost in the five-
and 10-year follow-up studies [6,7]. Similarly, in a study in UK
(The Lambeth Early Onset Team trial) [8] early intervention
programs improved short-term clinical outcomes but effects
were lost in the five-year follow-up when the intensive inter-
vention was stopped after two years [9]. The RAISE study
compared comprehensive multidisciplinary team-based treat-
ment approach to standard community care in the U.S. The
study showed that quality of life after two years improved
significantly among patients who received comprehensive
treatment compared to standard care [10].
Notable research on early intervention has also been con-
ducted in Asia. The Early Psychosis Intervention Program
(EPIP) in Singapore [11] and Early Assessment Service for
Young People with Early Psychosis (EASY) in Hong Kong [12]
have shown better outcomes, reduced suicide rates and
cost-effectiveness compared to traditional care.
Thus after the development of the new paradigm in first-
episode psychosis treatment, research on early intervention
has shown significant positive effects on psychopathological,
functional and quality-of-life outcome measures [13] and it
has been shown to be superior to traditional care [4]. The
effects reported have however been short-term, sustained
mostly for the first 2 years during the intensive intervention
and tending to diminish long-term [4]. Nevertheless, the
early intervention approach has been around for just over
CONTACT Karola Peebo karola.peebo@gmail.com North Estonia Medical Centre, Psychiatry Clinic, Paldiski Road 52, Tallinn 10617, Estonia
ß2021 The Nordic Psychiatric Association
NORDIC JOURNAL OF PSYCHIATRY
https://doi.org/10.1080/08039488.2021.1946139

two decades, and therefore still only limited information
about the long-term effects is available [14].
The establishment of early intervention services in the
Nordic countries inspired the opening of a specialized
department for integrative treatment in 1998 in the
Psychiatry Clinic in Tallinn, Estonia. Mainly influenced by the
Finnish National Schizophrenia Project with its integrated
multidisciplinary approach [15]. Although there is substantial
evidence to support implementation of early intervention
services [4,13], the integrative treatment program in Tallinn
still remains one of the few phase-specific early intervention
programs for first-episode psychosis in the Central and
Eastern European region [16]. The current analysis will inform
on the long-term effects of the integrative treatment pro-
gram in a patient sample formed to assess the efficacy of
the program, presenting results from the initial effectiveness
study and the first results of a 10-year follow-up. To our
knowledge, this is the first study on long-term effects of
early intervention in psychosis in the Central and Eastern
European region.
Participants and methods
Participants
The sample was composed of first-episode psychosis patients
admitted to the Tallinn Psychiatric Hospital (now North Estonia
Medical Centre Psychiatric Clinic) since March 2004 to February
2008 and treated in the first-episode psychosis integrative treat-
ment department. Patients included were in the age range of
18–55 with the mean age of 29, and had a diagnosis of schizo-
phrenia spectrum disorder (F20–F29). Double diagnosis patients
were excluded from the study. The total number of subjects
included in the study was 199 from which 107 subjects (47
males and 60 females) attended all re-assessments over the
two-year follow-up period (Figure 1). All patients included in
the study signed the Informed Consent Form.
In 2018, a long-term follow-up was conducted.
Information was retrieved for 116 patients of the original
sample. A control group of 116 patients who did not receive
the intervention was retrospectively formed of the patients
of the clinic during the same period and with the same
inclusion criteria (double diagnosis patients were also
excluded from the control group), who received treatment in
other departments (mostly department for acute cases and
departments for sub-acute cases) and, therefore, did not
receive any specialized intervention. The control group was
matched with the intervention sample for gender and age.
Two control group patients had to be excluded owing to
missing data.
The Tallinn Medical Research Ethics Committee approved
the trial (no. 2379).
Intervention
Integrative treatment
The integrative treatment program included pharmacological
and psychosocial interventions offered by a multidisciplinary
team. The open-dialogue model with a family-centered
approach was used [15,17]. Patients were assigned a treat-
ment team on admission. The team consisted of a psych-
iatrist, a psychologist and a psychiatric nurse. The same team
followed the treatment of the patient during inpatient stay
and also during the outpatient treatment thus allowing the
continuity of care. The duration of the intervention was
two years.
Treatment program consisted of pharmacological treat-
ment, psychotherapy and rehabilitation. All patients were pre-
scribed second-generation antipsychotics. Patients additionally
received individual psychotherapy by their treatment team
psychologist. Psychotherapeutical interventions included cog-
nitive-behavioral and family and/or psychodynamic therapy,
from which most patients received one. In addition to individ-
ual psychotherapy patients also took part of group therapies.
Two times a week patients participated in a computer-based
cognitive remediation program Cogpack Software
V
R
[18,19].
Once a week there was a metacognitive therapy group to
help improve socio-cognitive skills and provide psychoeduca-
tional information in a peer-group setting. The program also
offered individual and group art therapy. Cognitive remedi-
ation and metacognitive therapy were started during hospital-
ization and continued during outpatient visits as needed.
Families of the patients were involved as soon as possible
after admission and were offered psychoeducation and family
therapy. The treatment team also collaborated with rehabilita-
tion service providers, social and vocational rehabilitation serv-
ices were offered to patients.
Treatment as usual
During the inpatient treatment period the patient was seen
by the psychiatrist and/or psychologist. Minimal amount of
psychosocial intervention was offered (individual and group
psychotherapy, cognitive remediation and family involve-
ment were infrequently offered and not a systematic part of
treatment as usual compared to the intervention group). For
outpatient treatment, the patient was referred to an out-
patient psychiatric clinic/unit at their place of residence to
get the prescription filled. No or minimal psychotherapeutic
intervention was used during outpatient treatment. If
needed, the patient received a referral to a rehabilitation
center. All patients were treated with antipsychotics.
Assessments
Recruitment period and two-year follow-up
Socio-demographic parameters were collected by the psy-
chiatrists during interviews with patients and relatives.
Symptomatic and functional outcome measures were
assessed using following instruments.
The Brief Psychiatric Rating Scale (BPRS) is a rating scale
used to measure psychiatric symptoms, such as depression,
anxiety, hallucinations and unusual behavior. Each symptom is
rated 0–6 and a total of 18 symptoms are scored [20,21,22].
The Global Assessment of Functioning (GAF) is a numeric
scale used to rate subjectively the social, occupational and
2 K. PEEBO ET AL.

psychological functioning of an individual, e.g. how well one
is meeting various problems-in-living (American Psychiatric
Association, 1994).
The Q-les-Q comprises eight subscales, including physical
health, feelings, work, household chores, studies, leisure activ-
ities, social relationships and general life quality subscale. The
subject rated her/his satisfaction and quality of life on a five-
point scale. If a subject was not working or studying the cor-
responding subscale was skipped (Endicott et al., 1993).
Socio-demographic factors such as education, accommo-
dation and employment status. Assessments were done at
admission and 6 (except Q-les-Q), 12 and 24 months
after discharge.
Long-term follow-up
We selected the following outcome measures: patient spend-
ing any time in supported housing (yes/no), total duration of
employment in months, total income subject to social tax,
mean number of days in psychiatric hospital, readmissions
and deaths. All data for the follow-up study were collected
from national registries and databases: Estonian Health
Insurance Fund (rehospitalization, the most recent F20–F29
diagnosis, medication used), Estonian Tax and Customs Board
(employment and income subject to social tax), Population
Register (information about education), Social Insurance Board
(rehabilitation services including supported living), Estonian
Causes of Death Registry (cause and time of death). Data
were anonymized and coded at the Estonian Health Insurance
Fund using the personal ID number. The Estonian Data
Protection Inspectorate approved using data from national
registries and databases (approval no 2.2-/18/34).
Statistical analysis
Chi-square tests were used in intergroup comparisons of cat-
egorical variables. For continuous data two samples t-test
and the repeated measures ANOVA with a Bonferroni
correction for pairwise comparisons were used. All statistical
analyses were two-tailed and pvalues lower than .05 were
considered as statistically significant. Data analyses were car-
ried out using the Statistical Package for the Social Sciences
version 26.0 (SPSS Inc., Chicago, IL).
Results
Early assessment
Baseline socio-demographic and clinical characteristics are
presented in Table 1. Patients in both treatment conditions
were similar with no significant demographic differences for
any of the variables, except for occupational status. Table 2a
presents the results of the two-year follow-up of the inte-
grated treatment program (for the 107 patients who
attended all follow-ups, data for all the patients who partici-
pated at baseline and at subsequent follow-ups are pre-
sented in Table 2b). Substantial symptomatic improvement
(BPRS score reduction >50%) was achieved after 6 months of
treatment (p<.0001); further improvement was observed by
the end of the first year, and the BPRS scored remained sta-
ble in the second year. The quality of life by Q-les-Q was sig-
nificantly higher after 12 months than at the beginning of
the treatment (p<.0001) with a tendency to further improve
in the second year. The GAF was significantly improved at
6 months (p<.0001) and continued to improve throughout
the observation period. After 2 years, employment was sig-
nificantly higher than at baseline, increased by 14% (from
43.9% at baseline to 57.9% at the two-year follow-up).
Ten-year follow-up
One hundred and sixteen patients from the early assessment
with all the necessary data were included in the long-term
follow-up (Figure 1). We decided to include patients who
were part of the intervention for the entire duration of
24 months. We excluded the patients who dropped out of
Table 1. Baseline social and clinical characteristics of patients in the initial study group, patients who received treatment as usual (control group) and patients
who received integrated treatment (intervention group) for first-episode psychosis.
Characteristics
Early assessment group
N¼199 (%)
Long-term follow-up
Control group N¼114 (%) Intervention group N¼116 (%)
Age at admission, mean 28.4 30.3 29.2
Gender
Male 91 (45.7) 57 (50) 57 (49.1)
Female 108 (54.3) 57 (50) 59 (50.9)
Education, years, mean 13.2
Employment
Employed 88 (44.2) 42 (36.8) 50 (43.1)
Unemployed 57 (28.6) 62 (54.4) 47 (40.5)
Student 28 (14.1) 8 (7) 18 (15.5)
Permanent incapacity for work 1 (0.5) 0 0
No answer 25 (12.6) 2 (1.8) 1 (0.9)
ICD-10 diagnosis
Schizophrenia 28 (14.1) 33 (28.9) 21 (18.1)
Schizotypal disorder 1 (0.5) 3 (2.6) 0
Delusional disorder 10 (5) 5 (4.4) 4 (3.4)
Acute psychotic disorder 154 (77.4) 60 (52.6) 89 (76.7)
Schizoaffective psychosis 6 (3) 11 (9.6) 2 (1.7)
DUP
a
(months, mean) 9.3 (S.D.15.3)
(N¼169)
––
a
Duration of untreated psychosis.
NORDIC JOURNAL OF PSYCHIATRY 3

Table 2a. Outcomes for patients (N¼107, who attended all the follow-ups) who received integrated treatment (intervention group) for first-episode psychosis at baseline, 12 months and 24 months after admission.
Admission/baseline 6 months
pValue
(baseline vs. 6 m) 12 months
pValue
(6 m vs. 12 m) 24 months
pValue
(12 m vs.24m)
pValue
(baseline vs. 24 m)
% taking AP
a
100 96.3 .04 (v
2
¼4.1) 90.6 .1 (v
2
¼2.8) 85.8 .3 (v
2
¼1.1) <.0001 (v
2
¼16.1)
Mean no of psychiatric bed days
b
(SD) 35.1 (19.9) 5.4
(14.6)
<.0001 14.7
(29.9)
.001 24.1
(39)
<.0001 .046 (F(3, 318) ¼36.13)
BPRS mean score (S.D.) 37.5 (11.3) 17.2 (16.3) <.0001 14.5 (15.8) .93 14.2 (17.2) 1.0 <.0001 (F(3, 318) ¼73.7)
GAF mean score (S.D.) 33.5 (12.2) 62 (17.7) <.0001 65 (16.9) .5 67.1 (17.1) .9 <.0001 (F(3, 318) ¼165.39)
Q-les-Q mean score (SD) 46.5 (10.6) ––55.8 (10.2) –57 (11.9) .5 <.0001 (F(2, 196) ¼38.52)
Employment% 43.9 43.9 1.0 47.7 .6 (v
2
¼0.3) 57.9 .13 (v
2
¼2.3) .04 (v
2
¼4.2)
Unemployment%
c
29.9 11.3 .001 (v
2
¼11.4) 8.4 .5 (v
2
¼0.5) 1.9 .03 (v
2
¼4.7) <.0001 (31.5)
Permanent incapacity for work% 0.9 22.6 26.2 26.2
Comparison of the outcome measures at baseline and at 24 months.
a
Compliance was assessed by the treating psychiatrist.
b
Mean no of psychiatric days: baseline –first hospitalization; 12 months –number of days spent in a psychiatric hospital during the first 12 months after the first
hospitalization, i.e. excluding the first hospitalization days; 24 months –number of days spent in a psychiatric hospital during the second year, i.e. 12–24 months.
c
Unemployment rate decreased largely due to permanent incapacity for work granted to patients by the Estonian Unemployment Insurance Fund.
Table 2b. Outcomes for patients (all patients that participated in different follow-up) who received integrated treatment (intervention group) for first-episode psychosis at baseline, 12 months and 24 months
after admission.
Admission/baseline
(n¼199)
6 months
(n¼166)
pValue
(baseline vs. 6m)
12 months
(n¼154) pValue (6 vs. 12 m)
24 months
(n¼107)
pValue
(12 vs. 24 m)
pValue
(baseline vs. 24 m)
% taking AP
a
100 93.9 <.0001 (v
2
¼13.6) 87.4 .06 (v
2
¼3.7) 84.8 .51 (v
2
¼0.4) <.0001 (v
2
¼33.5)
Mean no of psychiatric bed days
b
39.3 (22.4) 4.96 (13.2) <.0001 (t¼17.3) 13.99 (28.7) <.0001 (t¼3.7) 24.1 (39) .012 (t¼2.5) <.0001 (t¼4.3)
BPRS mean score 35.8 (11.7) 15.1 (11.4) <.0001
(t¼16.6)
13.1 (10.6) .12 (t¼1.6) 14.2 (17.2) .35 (t¼0.9) <.0001
(t¼18.1)
GAF mean score 33.4 (12.5) 60.9 (18.2) <.0001
(t¼16.6)
65.2 (15.6) 0.03
(t¼2.2)
67.1 (17.1) .07
(t¼1.8)
<.0001
(t¼22.2)
Q-les-Q mean score 47.6 (11.3) ––56.6 (10.5) –57 (11.9) .68
(t¼0.4)
<.0001
(t¼7)
Employment% 44.2 45.7 .77 (v
2
¼0.9) 47.7 0.8 (v
2
¼0.8) 57.9 .09
(v
2
¼2.8)
.02
(v
2
¼5.2)
Unemployment%
c
28.6 9.9 <.0001
(v
2
¼20.4)
7.3 0.4
(v
2
¼0.6)
1.9 .05 (v
2
¼3.7) <.0001 (v
2
¼32.1)
Permanent incapacity for work% 0.5 24.7 <.0001 (v
2
¼52) 25.8 0.9 (v
2
¼0.02) 26.2 .9
(v
2
¼0.02)
<.0001
(v
2
¼53.4)
a
Compliance was assessed by the treating psychiatrist.
b
Mean no of psychiatric days: baseline –first hospitalization; 12 months –number of days spent in a psychiatric hospital during the first 12 months after the first hospitalization, i.e. excluding the first hospitalization
days; 24 months –number of days spent in a psychiatric hospital during the second year, i.e. 12–24 months.
c
Unemployment rate decreased largely due to permanent incapacity for work granted to patients by the Estonian Unemployment Insurance Fund.
4 K. PEEBO ET AL.

the treatment before because they did not receive the full
possible benefits of the intervention. It is possible that the
patients who dropped out were more severely ill.
For this reason, we compared patients at the 12-month
follow-up to see if there is any clinically significant difference
between patients who stayed in the study (n¼107) and the
patients who dropped out (n¼42) after 12 months. We did
not see any significant differences between these patients
when we compared BPRS (mean score of 14.2 for patients
who stayed vs. 16.9 for patients who dropped out, p¼.5)
and GAF (mean score of 65 for patients who stayed vs. 66
for patients who dropped out, p¼.9) scores or diagnoses
(14% of patients were diagnosed with schizophrenia out of
patients who stayed vs. 14.9% out of patients who
dropped out.
Diagnoses at the 10-year follow-up are presented in Table
3. There had been more patients with a diagnosis of schizo-
phrenia in the control group at baseline (28.9 vs. 18.1%;
Table 1). This difference disappeared over time and there
was 45% of patients with a diagnosis of schizophrenia in
both groups after 10 years. A fraction of subjects (14.9% in
the control group and 11.2% in the intervention group) did
not have any chronic psychiatric disorder after 10 years.
These were predominantly patients who received an acute
psychotic disorder diagnosis at baseline and did not have a
relapse and therefore did not receive any further diagnosis.
Significantly fewer patients in the intervention group had
been in supported housing compared to the control group
(Table 4). Patients in the intervention group spent signifi-
cantly more time working during the follow-up period than
patients in the control group (76.3 vs. 47.1 months in total,
p<.0001). Consequently, patients in the intervention group
had significantly larger incomes over the follow-up period
(p¼.001). Fifteen patients (13.2%) in the control group and
seven patients (6%) in the intervention group died, but the
difference did not reach the conventional level of statistical
significance. Causes of death are shown in Table 5. There
was no statistically significant difference in the number of
days spent in psychiatric hospital or the readmissions. 36.8%
(N¼42) patients in the control group and 22.4% (N¼26) in
the intervention group were hospitalized only once during
the follow-up period. Of 25.4% (N¼29) in the control group
and 29% (N¼34) were hospitalized more than 5 times dur-
ing the follow-up period.
Discussion
We conducted a naturalistic effectiveness study in a real-
world clinical setting. In the early assessment phase, a group
of patients with a first-episode psychosis that received early
intervention were followed and assessed over a two-year
period. Patients who received early intervention achieved sig-
nificant improvement of psychosis symptoms, quality of life
and functioning during the first two years of the treatment.
Employment rate was also substantially higher after two
years and unemployment decreased more than 10 times.
The large effect on employment is probably due to rehabili-
tation being important focus of the intervention. The treat-
ment team ensures that the patients get vocational and
social rehabilitation services according to their needs.
Rehabilitation team members are also included in the treat-
ment team meetings and the team follows up on patients
educational and vocational progress.
There were more patients with the diagnosis of schizo-
phrenia at first admission in the control group than in the
intervention group (28.9 vs. 18.1%). Patients in the control
group were mostly treated in the department for acute cases
and departments for sub-acute cases. It is possible that the
diagnostic discrepancy at baseline is due to different
approaches to diagnosing first episode psychosis between
departments. Psychiatrists in the departments for mostly
chronic patients are likely to be more prone to diagnosing
schizophrenia at first admission. Psychiatrists in the first epi-
sode psychosis department instead tend to diagnose acute
and transient psychotic disorders at first admissions. It is
however possible that patients in the control group had lon-
ger durations of untreated psychosis (DUPs), therefore the
time criteria for schizophrenia diagnosis were met for more
Table 3. ICD-10 diagnoses for patients who received treatment as usual (con-
trol group) and integrated treatment (intervention group) for first-episode
psychosis at 10-year follow-up.
ICD-10 diagnosis
Control group
N¼114 (%)
Intervention group
N¼116 (%)
Schizophrenia 52 (45.6) 53 (45.7)
Schizotypal disorder 2 (1.8) 1 (0.9)
Delusional disorder 4 (3.5) 3 (2.6)
Acute psychotic disorder 5 (4.4) 6 (5.2)
Schizoaffective disorder 17 (14.9) 28 (24.1)
Non-psychotic disorder 2 (1.8) 5 (4.3)
No diagnosis 17 (14.9) 13 (11.2)
Dead 15 (13.2) 7 (6)
Table 4. Comparison of outcome measures for patients who received treatment as usual (control group) or integrated treatment (intervention group) for first-
episode psychosis.
Control group (N¼114) Intervention group (N¼116) t/v
2
pValue
Patients spending any time in supported housing 17 6 6.06 .012
Total duration of employment in months, mean (SD) 47.1 76.3 3.83 <.0001
(56.5) (59.1)
Total income subject to social tax (EUR), mean (SD) 23,850.2 46,265.6 3.42 .001
(41,008.3) (57,084.8)
Deaths 15 7 3.37 .053
Mean no. of days in psychiatric hospital
a
(SD)
129.85 138.74 0.419 .321
(177.47) (142.51)
Readmissions
b
(SD) 4.56 4.52 0.068 .95
(5.65) (4.16)
a
Mean number of days spent in a psychiatric hospital during the follow-up period.
b
Mean number of readmissions in a year during the follow-up period.
NORDIC JOURNAL OF PSYCHIATRY 5

patients. Unfortunately, the DUP for the control group
patients is not possible to assess retrospectively.
Nevertheless, the diagnostic discrepancy disappeared over
time, at the 10-year follow-up the number of patients with a
diagnosis of schizophrenia was similar (45.6% in the control
group and 45.7% in the intervention group).
Although there is convincing evidence on the short-term
benefits, not much is known about the long-term effects of
early interventions in psychosis [14]. Therefore, we con-
ducted a long-term follow-up of approximately 10 years and
formed a control group retrospectively to compare long-
term effects of the intervention to treatment as usual. We
opted for registry-based data for the 10-year follow-up. The
Danish OPUS trial [7] and the Lambeth Early Onset Team trial
[9] also used data from national registries as part of their
long-term follow-ups. Since the results on scales, such as
BPRS, GAF, etc., are not available in the registers, we could
not compare the early assessment outcomes with the control
group. Instead, we focused on long-term outcomes that
have been previously used in early intervention research.
This study provides further support to the notion that
early intervention for first-episode psychosis has significant
long-term benefits, such as increased employment and inde-
pendent living. These effects have previously been reported
in some long-term studies. The 10-year EASY follow-up study
in Hong Kong reported that early intervention patients had
significantly more months of total employment (full time and
part time) than the standard care group [12]. The 10-year fol-
low-up of the OPUS study reported that patients in the treat-
ment as usual group spent more days in supported housing
than patients in the intervention group, but there was no
significant difference in employment and average income
between groups [7].
All income derived from employment, business, etc., is
subject to social tax, therefore, it demonstrates official
employment of patients and also their contribution to the
society. This functional outcome measure also revealed the
benefits of the early intervention. Among the long-term out-
come studies, only the OPUS 10-year follow-up has used
income as an outcome measure, but this study did not find
any significant differences between the early intervention
and treatment as usual groups [7].
There was no statistically significant between-groups dif-
ference in deaths, but there were two times more deaths in
the treatment as usual group. The OPUS 10-year follow-up
did not demonstrate any difference in mortality between
groups (early intervention ¼5.1%, treatment as usual-
¼5.5%). The EASY follow-up reported significantly lower
completed suicide rate in the early intervention group (early
intervention ¼4.4%, standard care ¼7.5%). In our sample,
nine patients in the control group and four patients in the
intervention group died of unnatural causes. This could
mean that the early intervention had an effect on mortality
and especially suicidality, but the study was underpowered
to detect it. Any hypothesized effect might be due to the
intensive out-patient care and the psychoeducational and
metacognitive interventions offered.
Table 5. Causes of death for the patients who received treatment as usual (control group) and integrated treatment (intervention group) for first-episode psych-
osis at 10-year follow-up.
Causes of death (ICD-10 codes) Control group (n¼114) n(%) Intervention group (n¼116) n(%) pValue
All causes 15 (13.2) 7 (6) 0.053
Natural causes (A00–Q99) 4 (3.5) 2 (1.7) –
Neoplasms (C00–D48) 0 1 (0.9)
Diseases of the circulatory system (I00–I99) 3 (2.6) 1 (0.9)
Diseases of the respiratory system (J00–J99) 1 (0.9) 0
Unknown causes (R00–R99) 2 (1.8) 1 (0.9) –
Unnatural causes (V01–Y89)
a
9 (7.9) 4 (3.4) 0.12
a
Unnatural causes (V01–Y89): Intervention group: poisoning, undetermined intent (n¼1), accidental poisonings and 1 intentional self-harm with a sharp
object (n¼2).
Control group: poisoning, undetermined intent (n¼1), accidental poisonings (n¼2), intentional poisoning/hanging/self-harm (n¼4), accidental fall from a
building (n¼1) and assault (n¼1).
Included at baseline
(n=199)
Included at 12 months (n=154)
Included at 24 months (n=107)
Lost to follow-up (n=33)
-Refused to participate (n=6)
-Lost contact (n=20)
-Relocated (n=7)
Lost to follow-up (n=12)
-Refused to participate (n=2)
-Lost contact (n=8)
-Relocated (n=2)
Lost to follow-up (n=47)
-Change of diagnosis (n=2)
-Refused to participate (n=11)
-Lost contact (n = 27)
-Relocated (n=7)
Included at 6 months (n=166)
Included at the 10-year follow-up (intervention
group n=116)
-107 patients from the 24-month follow-up
-9 patients who completed the 2-year
intervention but did not attend all final
assessments
Figure 1. Flow of patients through the assessment phases of the study.
6 K. PEEBO ET AL.

One of the main limitations of this study is the absence of
a control group in the early assessment phase of the study,
therefore, we can only show the effects of the intervention
on patients who received it but cannot compare the short-
term effects to treatment as usual.
Another major limitation is that for the long-term follow-
up, we decided to include patients who were part of the
intervention for the entire duration of 24 months (n¼116).
We excluded the patients who dropped out of the treatment
before because they did not receive the full possible benefits
of the intervention. It is possible that the patients who
dropped out were more severely ill. For this reason, we com-
pared patients at the 12-month follow-up to see if there is
any clinically significant difference between patients who
stayed in the study (n¼107) and the patients who dropped
out (n¼42) after 12 months. We did not see any significant
differences between these patients.
The difficulty to ensure the comparability of the retro-
spectively formed control group and the intervention group
is and the small sample size is also imitations of this study.
Despite these limitations, this study also has some import-
ant strengths. There still are not a lot of long-term studies
on early intervention in first-episode psychosis and this study
might help to fill this gap a little. We plan to analyze other
outcome measures of these two groups in the future. The
long-term follow-up is registry-based which enables the com-
plete follow-up of the entire selected sample.
Conclusion
This study demonstrated short-term benefits of the early
intervention program for first-episode psychosis patients in
Tallinn, Estonia. Some long-term effects were also shown
which included functional outcomes, such as supported
housing usage and employment. This is the first long-term
case-control study of early intervention of psychosis in
Eastern Europe.
Acknowledgments
The authors thank all the patients who participated in the study and the
first-episode psychosis integrative treatment department of the North
Estonia Medical Centre. We would also like to thank K. K€
u€
unarpuu, K.
Troost, K. Orav, E. Eding, K. Aadamsoo, K. Eino, K. Konsap, M. Vonk, L.
H€
urden, K. Bunder and L. Tserepanov who made the early assessment
phase of the study possible. This study was initially part of an inter-
national research project ‘Multicenter Study of First Incident Psychosis’
(including 16 treatment facilities from Scandinavian and Baltic countries).
Disclosure statement
The authors declare no potential conflict of interest.
Notes on contributors
Karola Peebo, MD, is a psychiatrist in the First-Episode Psychosis
Integrative Treatment Department of the North Estonia Medical Centre.
Erika Saluveer, MD, is a psychiatrist and Head of the First-episode
Psychosis Integrative Treatment Department of the North Estonia
Medical Centre.
Harri K€
u€
unarpuu is a clinical psychologist in the First-Episode Psychosis
Integrative Treatment Department of the North Estonia Medical Centre.
Teele Orgse, MD, is a healthcare quality specialist and worked as a
Clinical Data Analyst in the North Estonia Medical Centre.
Jaanus Harro, MD, PhD, is Professor and Chair,
Neuropsychopharmacology, at the University of Tartu, and Research
Associate at the Psychiatry Clinic, North Estonia Medical Centre.
ORCID
Karola Peebo http://orcid.org/0000-0002-6847-8444
Jaanus Harro http://orcid.org/0000-0002-4484-2096
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