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The OPUS –trial:
A randomised multicentre single-
blinded trial of specialised assertive
treatment versus standard treatment for
patients with a first episode of psychotic
illness – five-years follow-up.
Professor Merete Nordentoft
Psychiatric Center Bispebjerg, Copenhagen University
www.opus-kbh.dk
The Danish OPUS Trial: A two-site randomised clinical trial of
assertive specialised psychiatric treatment
First episode psychosis
Five-year follow-up
• The name OPUS was taken from the music
• It means: Piece of work
• We wanted to indicate the need of coordination of different elements in psychiatric treatment
• -and that these elements play together
• We hoped to build an instrument that could play many different keys and tunes
• We conducted a pragmatic trial
A long awaited guest
� A long awaited guest who you want to
feel welcome and at home during a long
visit.
� A collaborator, whose insights and
attitudes are decisive for the outcome.
� An individual with personal preferences
that should be taken into account in the
treatment to the greatest extent possible.
Specialised Assertive
Intervention by OPUS team
•Assertive Community Treatment
–(staff: patient ratio1:10)
•Psychoeducational multi family groups
•Social skills training
The OPUS team
• Psychiatrist
• Psychiatric nurse
• Psychologist
• Social worker
• Vocational therapist
• Labour market/ educational guide
Assertive Community Treatment
•Multidisciplinary team, caseload 1:10
•Team follows the patients during in - and
outpatient treatment
•Flexible frequency of contact (weekly)
•Home visits
•Coordinate different institutions involved in
the treatment of the patient. GP, somatic
department, creditors and social services.
For instance how to respond to an unpleasant official letter
Or how to respond when neighbours complain about
too much wornout furniture placed in the corridor
Or what kind of job training will be relevant?
The OPUS Program for
involving the family:
• Consequently involving families
• Survival skills workshops for relatives
• Single family sessions with crisis intervention with
and/or without the patient
• McFarlanes model for psychoeducational multi-
family groups, every second week for 1½ year.
• On – going possibility for contact to the patient’s
primary team member
Attitudes towards relatives:
•The closest collaborating partners
•Who can be of invaluable help
•Who are very involved in relation to the patient
•A ressource that cannot be equalled
The multi-family group
• 4 - 6 patients and their relatives
• The group meets for 1½ years
• The group meets every second week for
1½- hour meetings
• The method is problem solving
Common problems
•Medication side effects
• Drug abuse
• Job seeking
• Going to school
• Moving away from home
• Maintaining relations
• Conversation
• Parents holiday
The approach
The intervention is personal and warm:
•Show you are interested
•Create a bond between you and the family
•Serve as the advocate of the family
•Create a respectful and not too asymmetric alliance
GuidelinesA list of guidelines and ideas for the family, which can make
family life run more smoothly• Take it easy. It takes time to recover. It is important to rest.
• Keep cool. It is good to be eager, but it can be too much.
• Give room to each other. It is important to have time and room for one’s self.
• Set limits. Everybody needs to know the house rules. It is ok to ask for help, and it is ok to say no.
• Try to accept things, which cannot be changed. Let some things pass. Violence must never be accepted.
• Try to simplify everyday life and conversation. Make the communication clear, calm and positive.
• Be aware of early warning signals for relapse of psychosis. Talk with the contact person about this.
• Solve one problem at a time. Let changes come gradually.
• Lower your expectations. Use a personal measure. Compare this month with last month.
Inclusion CriteriaAge 18-45
A diagnosis (ICD10 research criteria) of F2: schizophrenia, schizotypal disorder, delusional disorder, acute
psychosis, schizoaffective psychosis or unspecific non-organic
psychosis
Patients have so far not had adequate treatment,
defined as 12 weeks of anti-psychotic medication
Assessments• SCAN (Schedule for Clinical Assessment in Neuropsychiatry)
• SAPS (Schedule for Assessment of Positive Symptoms)
• SANS (Schedule for Assessment of Negative Symptoms)
• GAF (function and symptoms)
• Demographic data including educational, employment and
housing status
• Lancashire Quality of life Scale
• Client Satisfaction Questionnaire
• Life Chart Schedule
• Cognitive test (only at 5 years follow-up)
Registerbased follow-up
• Complete case records from all mental health services in the catchment areas
• Danish Psychiatric Central Case Register
• Cause of Death Register
• Central Civil Register (CPR)
• Statistic Denmark
• Database with all addresses for psychiatric nursing homes and staffed group homes
547 patients included
and randomised
272 patients allocated to
standard treatment
275 patients allocated to
OPUS team treatment and
treated for two years.
All patients were offered
standard treatment
for another three years
301 interview after
five years (56%)
Satisfaction with treatment 2 yWould you recommend this treatment to a friend?
0
10
20
30
40
50
60
Definitely I think so I don't think so Definitely not
OPUS team
Standard
DropDrop--outout
No outNo out--patient treatmentpatient treatment
0
5
10
15
20
25
30
35
1 år 2 år
Pro
cen
t
OPUS
Standard
Petersen et al, BMJ 2005
Psychotic dimensionPsychotic dimensionMean values
0
0,5
1
1,5
2
2,5
3
Baseline 1y 2y 5y
OPUS Standard
P=0.02 P=0.02 P= 0.31
Bertelsen et al, Arch Gen Psych 2008
Negative dimensionNegative dimensionMean values
0
0,5
1
1,5
2
2,5
Baseline 1y 2y 5y
OPUS Standard
P<0.001P<0.001 P=0.7
Bertelsen et al, Arch Gen Psych 2008
0
5
10
15
20
25
30
Baseline 1 y 2 y 5 y
OPUS team Standard
P = 0.03 P=0.04
Substance abuseSubstance abuse
Comorbid substance abuse (%)
P=0.49
Use of beddays during and after the
OPUS-trial
0
10
20
30
40
50
60
70
First two years Next three years
OPUS
Standard
Bertelsen et al, Arch Gen Psych 2008
Use of supported housing
Living in an institution
0
2
4
6
8
10
12
Supported housing 2y Supported housing 5y
Perc
en
t
OPUS
Standard
Use of supported housing
Living in an institution
0
20
40
60
80
100
120
First two years Nex three years
Days
OPUS
Standard
Bertelsen et al, Schiz res, 2008
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2y 5y
7,912,5
72,652,8
7,5
15,2
19,5 19,4
Prognosis for patients with first episode psychosis after two and
five years
Recovery: GAF-F>60, remission and working or studying
Remission of psychotic and negative symptoms
Non-remission or not working or studying
Institutionalized: Living in supported housing or hospitalized more than 6 month last year
Probality of death (all causes) in the two
treatment groups as a function of time (days)
Hazard Function
TIME
200010000
Cu
m H
aza
rd,04
,03
,02
,01
0,00
-,01
Treatment group
Standard treatment
Standard treatment
-censored
Integrated treatment
Integrated treatment
-censored
Civil registration
system:
547 patients
RR 0.6 (0.2-1.6), P=
0.3
Power calculation:
1522 patients in each
treatment condition
necessary to detect a
difference between 2
% and 4 % mortality
Survival in the first 5 years
Probality of death by suicide in the two
treatment groups as a function of time (days)
Hazard Function
TIME
200010000
Cu
m H
aza
rd
,016
,014
,012
,010
,008
,006
,004
,002
0,000
-,002
Treatment group
Standard treatment
Standard treatment
-censored
Integrated treatment
Integrated treatment
-censored
Suicides in the first 5 years
Bertelsen et al,
Br J Psych, 2007
The Danish OPUS Trial
Conclusion:
• Psychotic and negative symptoms and substance
abuse was significantly better after two years of
intervention.
• Difference disappeared when patients in OPUS
treatment were transferred to standard treatment
after two years
• No difference between treatment groups at five-
year follow-up
The Danish OPUS Trial
Conclusion:
• Significant more satisfaction with treatment in
OPUS-team treated group after two-years
• Significantly better adherence in OPUS-team
treated group
The Danish OPUS TrialConclusion:
• Number of bed days was reduced with 22 percent in OPUS team group compared with standard treatment
• Even after the end of the experimental periode, patients in integrated treatment still had a lower use of bed days (17 percent lower)
• Fewer in the OPUS-treated group stayed in supported housing after five years
• OPUS treatment was cheaper and
better than standard treatment
Painkiller or driving licence
• Training effect
• Compensation
Rationale for early
assertive intervention
Compensation Learning
Rationale for early
assertive intervention
Compensation Learning
Rationale for early
assertive intervention
Compensation Learning
The relatives
• Effect after one year specialised assertive
treatment
Relatives stress-score, one-yearSocial Behaviour Assessment Schedule
5687N =
Intervention
STIT
global index of distress, 1 year
2,5
2,0
1,5
1,0
,5
0,0
347061193
OPUS vs
ST:
P= 0.04
Jeppesen,
Br J Psych, 2005,
Vol 87,Suppl 48
OPUS
Knowledge about schizophrenia,
relatives, one-year follow-up
5283N =
Intervention
STIT
knowledge score
at 1 year
40
30
20
10
0
21217
181
OPUS vs ST:
P= 0.02
OPUS
Satisfaction with treatment,
relatives, one-year follow-up
5184N =
Intervention
STIT
sum-score
of satisfaction
40
30
20
10
0
150
91
2354740
14
T-test
mean diff =
4.26 (2.7-5.9)
p<0.001OPUS
“Did the treatment help you to a better
understanding of your mentally ill
relative?”
csq8
4321
Percent
60
50
40
30
20
10
0
Intervention
IT
ST
Not at all Not very much To some degree Much better
OPUS
Clinical implications
• Intensive early intervention programmes
should be implemented
• Not to induce unnecessary loss of hope for
patients since approximately 45 % can
expect to reach remission of symptoms after
two years
Deinstitutionalisation revisited
Should the most severely ill among first
episode psychosis patients be treated with
hospital based rehabilitation?
46
578 patients includedin the OPUS-trial
272 patients allocated to Treatment As Usual;
N=29 + N=243
275 patients allocated to
Integrated Treatment;
N=34 + N=241
Randomisation 1
94 patients randomised
Hospital-based Rehabilitation;
N=31
Figure 1. The randomisations
Treatment As Usual;
N=29
Randomisation 2
484 patients randomised
TreatmentAs Usual;
N=243
IntegratedTreatment;
N=241
Integrated Treatment;
N=34
Number of days in psychiatric department or supported
housing during five years for first episode psychotic
patients randomised to OPUS, standard treatment or
hospitalbased rehabilitation
0
50
100
150
200
250
300
First
year,supervised
setting
Second year,
supervised
setting
Third year,
supervised
setting
Fourth year,
supervised
setting
Fifth year,
supervised
setting
Nu
mb
er
of
da
ys
pe
r y
ea
r
OPUS
Standard
HBR
Now we have build
excellent services for
first episode psychosis
Now we have build
excellent services for
first episode psychosis
But, what about the rest
of mental health services?
The extension trial OPUS II
The critical period?
400 patients treated in OPUS in two years
200 patients are
transferred to
CMHC, ACT-teams
or primary care
200 patients
continue OPUS
treatment for another
three years
Project will start 2009
The extension trial OPUS II
Primary outcome measure:
•Remission of negative and psychotic symptoms
Secondary outcome measures:
•Psychotic and negative symptoms
•Substance abuse
•User satisfaction
•Adherence to treatment
•Compliance with medication
•Suicidal behaviour
•Use of bed days
•Ability to live independently
•Labour market affiliation
The extension trial OPUS II
Power calculation
Two-years follow-up: simultaneous remission of
both negative and positive symptoms 38 percent
in OPUS vs 25 percent in standard.
We want to detect if this difference can be
maintained until five years follow up.
With the two-sided alpha level of significance of
0.05 and with a power of 0.80, and 25 percent
attrition, we will need to include 200 patients in
each group
The OPUS Trial• Merete Nordentoft
• Maj-Britt Abel
• Pia Jeppesen
• Anne Thorup
• Lone Petersen
• Johan Øhlenschlæger
• Runa Munkner
• Mette Bertelsen
• Britt Morthorst
• Gry Secher
• Marianne Melau
• Per Jørgensen
• Torben Christensen
• Gertrud Krarup
• Phoung Le Quack
• Ole Mors
• Preben Mortensen
• Stephen Austin
Psychiatric Centre Bispebjerg and
Sct Hans,
University of Copenhagen
Psychiatric
Universityhospital, Risskov,
The Danish OPUS TrialFunding:
Danish Ministry of Health,
Danish Ministry of Social Affairs,
Danish Medical Research Council,
University of Copenhagen,
Copenhagen Hospital Corporation,
Danish Medical Research Council,
Aarhus County,
Copenhagen Municipality,
The Stanley Medical Research Institute
Slagtermester Wørzners Foundation.
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The
Danish
OPUS
trial
Thank you for your attention
