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OPUS; A sustainable treatment?

Mette Bertelsen, Bispebjerg University Hospital, Denmark

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The Danish OPUS Trial: A two-site randomised controlled trial of integrated psychiatric treatment

Mette Bertelsen, Bispebjerg University Hospital, Denmark

First episode psychosis

Five-year follow-up

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Treatment by OPUS teamTreatment by OPUS team The OPUS trialThe OPUS trial Results from Results from twotwo- and - and fivefive-years -years

follow-upfollow-up ConclusionConclusion

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The OPUS team

PsychiatristPsychiatrist Psychiatric nursePsychiatric nurse Social workerSocial worker

PsychologistPsychologist Occupational therapistOccupational therapist Vocational guideVocational guide

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Treatment by OPUS team

Assertive Community TreatmentAssertive Community Treatment

Psychoeducational multi family Psychoeducational multi family groupsgroups

Social skills trainingSocial skills training

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Assertive Community Treatment

Multidisciplinary teamMultidisciplinary teamContact during in - and outpatient Contact during in - and outpatient treatmenttreatmentFlexible frequency of contact Flexible frequency of contact (weekly)(weekly)Home visits Home visits Coordination of the GP, somatic Coordination of the GP, somatic department and social servicesdepartment and social services

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Family Treatment Educational workshop for Educational workshop for relatives.relatives.

Single family sessions with Single family sessions with crisis crisis intervention. intervention.

McFarlanes model for McFarlanes model for psychoeducational psychoeducational multi family multi family groups. groups.

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Social skills training

Coping with symptoms Coping with symptoms

Managing own medicationManaging own medication

Basic social skill training Basic social skill training

Problem solvingProblem solving

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The OPUS trialInclusion Criteria

• Age 18-45Age 18-45

• A diagnosis (ICD10 research criteria) of A diagnosis (ICD10 research criteria) of F2: F2: schizophrenia, schizotypal disorder, delusional schizophrenia, schizotypal disorder, delusional disorder, acute psychosis, schizoaffective psychosis or disorder, acute psychosis, schizoaffective psychosis or unspecific non-organic psychosisunspecific non-organic psychosis

• Patients have not had previously Patients have not had previously adequate treatment, defined as 12 adequate treatment, defined as 12 weeks of anti-psychotic medication weeks of anti-psychotic medication

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Assessments (1) SCAN (Schedule for Clinical Assessment in SCAN (Schedule for Clinical Assessment in

Neuropsychiatry)Neuropsychiatry) SAPS SAPS (Schedule for Assessment of Positive Symptoms)(Schedule for Assessment of Positive Symptoms) SANS SANS (Schedule for Assessment of Negative Symptoms)(Schedule for Assessment of Negative Symptoms) Gaf (function and symptoms)Gaf (function and symptoms) DemograDemographphic data including educational, employment ic data including educational, employment

and housing statusand housing status Lancashire Quality of life ScaleLancashire Quality of life Scale Client Satisfaction Client Satisfaction QuestionnaireQuestionnaire Life Chart ScheduleLife Chart Schedule Cognitive test (only at 5 years follow-up)Cognitive test (only at 5 years follow-up)

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Assessments (2) Complete case records from all Complete case records from all

mental health services in the mental health services in the catchment areacatchment areass

Danish Psychiatric Central Case Danish Psychiatric Central Case RegisterRegister

Cause of Death RegisterCause of Death Register

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547 patients included and randomised

272 patients allocated to standard treatment

275 patients allocated toOPUS team treatment

and treated for two years

All patients were offered standard treatment for

another three years

301 interviewed afterfive years (55%)

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547 patients included and randomised

272 patients allocated to standard treatment

205 interviewed after two years (75%)

Attrition: 62

275 patients allocated to OPUS team

164 interviewed aftertwo years (62%)

Attrition: 44

151 interviewed after five years (56%)

150 interviewed afterfive years (57%)

Attrition: 80 Attrition: 60

Baseline

2 y

5 y

Attrition: 26 Attrition: 46

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Characteristics of 547 Characteristics of 547 Patients, BaselinePatients, Baseline

Age, years (mean)Age, years (mean) 26.6 26.6 Male genderMale gender 59 %59 %Diagnosis of schizophrenia Diagnosis of schizophrenia 66 %66 %Secondary diagnosis substance abuseSecondary diagnosis substance abuse27%27%Duration of untreated psychosis 43 weeks Duration of untreated psychosis 43 weeks medianmedian

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OPUS Standard Sign

Out-patient contacts 1+2y, median 75 20 <0.001Family involved in treatment 1+2y 61 % 20 % <0.001Family psychoeducational gr. 1+2y 46 % 2 % <0.001Social skills training 1+2y 43 % 12 % <0.001

Outpatient visits, family Outpatient visits, family intervention and social skills intervention and social skills trainingtraining

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OPUS Standard Sign. ____________________________________________________

No out-patient visits,1y 4 % 15 % <0.001

No out-patient visits 2y 7 % 31 % <0.001

OR 0.2-0.3, NNT 4-8 

Non-adherance

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Negative dimensionMean values at follow-up

Negative symptoms

0

0,5

1

1,5

2

2,5

Baseline 1. Year 2. Year 5. Year

OPUS Standard

P<0.001

P<0.001 P=0.7

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Psychotic dimension Mean values at follow-up

Psychotic symptoms

00,5

11,5

22,5

3

Baseline 1. Year 2. Year 5. Year

OPUS Standard

P=0.02P=0.02 P= 0.31

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Secondary diagnosis of harm and dependence

0

5

10

15

20

25

30

Baseline 1. Year 2. Year 5. Year

Perc

ent

OPUS team

Standard

P = 0.03 P=0.04

Harm and dependenceMean values at follow-up

P=0.49

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Antipsychotic medicationOPUS Standard

Antipsych. med. 2 y 60 % 55 % Chi2,

P=0.23

Antipsych. med. 5 y 65 % 65 % ns

Dosis Atypical

Haloperidol-eqv 2 y 4.0 mg 4.9 mgT-test P=0.01

Haloperidol-eqv 5 y 2.8 mg 2.3 mg T-test

P=0.1

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Satisfaction with treatment 2 y

Would you recommend this treatment to a friend?

0

10

20

30

40

50

60

Definitely I think so I don't thinkso

Definitely not

OPUS team

Standard

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Remission five years after debut

- past two years  

OPUS team treatment

N=151

Standard treatment

N=150

Total

Episodic 21 (14%) 24 (16%) 45 (15%)

Continous 68 (45%) 66 (44%) 134 (44.5%)

Not psychotic

62 (41%) 60 (40%) 122 (40.5%)

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Use of bed days from baseline – 5y

  OPUS Standard

Sign.  Mean days in hospital 95 122 0.05(baseline-2y)

Mean days in hospital 59 710.34

(2y-5y)

Mean days in hospital 154 193 0.08

(baseline-5y)

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Cost-Benefit of OPUS Team-Treatment

Mean of Mean of 3939 bed days bed days (20%)(20%) saved for patients saved for patients in OPUS team treatment during five yearsin OPUS team treatment during five years

Saved cost of in-patient treatment for one Saved cost of in-patient treatment for one year: year:

7 million7 million DKK for 100 patients ( 930000 euro) DKK for 100 patients ( 930000 euro)

-more than enough to pay the wages of 10 staff -more than enough to pay the wages of 10 staff membersmembers

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Use of bed days amongst patients with a secondary

diagnosis of substance abuse

0

10

20

30

40

50

60

70

80

90

First 2 years Next 3 years

OPUS StandardP<0.05

P<0.05

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Independent housingbaseline – 5 years

  OPUS Standard

Sign. Not living independently (%) 7% 7% nsafter 2 years

Not living independently (%) 4% 10% 0.02 after 5 years

Days (mean) not living independently (0-2 years) 30 35 0.6

Days (mean) not living independently (2- 5 years) 57 102 0.05

28Figure 2. Probality of death (all causes) in the two treatment groups as a function of time (days)

Hazard Function

TIME

200010000

Cum

Haz

ard

,04

,03

,02

,01

0,00

-,01

Treatment group

Standard treatment

Standard treatment

-censored

Integrated treatment

Integrated treatment

-censored

Civil registration system: 547 patientsRR 0.6 (0.2-1.6), P= 0.3Power calculation:1522 patients in each treatment condition necessary to detect a difference between 2 % and 4 % mortality

Survival in the first 5 years

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OPUS; A sustainable treatment?

Driving licence or painkiller

Mette Bertelsen, Bispebjerg University Hospital, Denmark

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Conclusion (1) Significant reduction in symptoms Significant reduction in symptoms

after 2 yearsafter 2 years Significant reduction in drug- and Significant reduction in drug- and

alcohol misuse after 2 years alcohol misuse after 2 years Significantly higher satisfaction with Significantly higher satisfaction with

treatmenttreatment Low dose strategy succeededLow dose strategy succeeded Better adherence to treatmentBetter adherence to treatment

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Conclusion (2) When patients were transferred to When patients were transferred to

standard treatment after 2 years - standard treatment after 2 years - nono differerence between treatment differerence between treatment groups with regard to;groups with regard to;

- negative symptoms- negative symptoms - psychotic symptoms- psychotic symptoms - harm and dependence- harm and dependence

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Conclusion (3) Number of bed days were reduced Number of bed days were reduced

with a mean of 39 (20%) in OPUS with a mean of 39 (20%) in OPUS team group compared with team group compared with standard treatment after five yearsstandard treatment after five years

More patients from OPUS team live More patients from OPUS team live independently after 5 years independently after 5 years

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Clinical Implications Longer duration of treatment (3,4 Longer duration of treatment (3,4

or 5 years?)or 5 years?)

Transition from OPUS treatment to Transition from OPUS treatment to standard treatment?standard treatment?

Booster sessions?Booster sessions?

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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 Merete NordentoftMerete Nordentoft Pia JeppesenPia Jeppesen Maj-Britt AbelMaj-Britt Abel Anne Thorup Anne Thorup Lone PetersenLone Petersen Johan ØhlenschlægerJohan Øhlenschlæger Runa MunknerRuna Munkner Mette BertelsenMette Bertelsen Ralf HemmingsenRalf Hemmingsen

Per JørgensenPer Jørgensen Torben ChristensenTorben Christensen Gertrud KrarupGertrud Krarup Phuong Le QuachPhuong Le Quach Ole MorsOle Mors Preben Bo MortensenPreben Bo Mortensen

H:S, Bispebjerg and Sct Hans Hospital, University of Copenhagen

Psychiatric Hospital, Risskov and Center for Registerbased ResearchUniversity of Aarhus

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547 patienter inkluderet og randomiseret

272 patienter allokeret til standard behandling

205 interview efter to år (75%)

Frafald: 624 selvmord1 ukendt dødsårsag1 død v. ulykke33 afviste interview9 flyttet langt væk10 kunne ej spores4 uvist

275 patienter allokeret til OPUS team

164 interview efterto år (62%)

Frafald: 441 selvmord21 afviste interview10 flyttet langt væk6 kunne ej spores6 uvist

151 interview efter fem år (56%)

150 interview efterfem år (57%)

Frafald: 802 selvmord2 ukendt dødsårsag1 død v. ulykke48 afviste interview1 flyttet langt væk26 kunne ej spores

Frafald: 601 naturlig dødsårsag3 ukendt dødsårsag32 afviste interview5 flyttet langt væk19 kunne ej spores

Baseline

2 y

5 y

Frafald: 2613 afviste int. 4 flyttet6 ej spores3 uvist

Frafald 4622 afviste int.7 flyttet12 ej spores5 uvist