1. 1 OPUS; A sustainable treatment? Mette Bertelsen, Bispebjerg University Hospital, Denmark

2. 2 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

3. 3 Treatment by OPUS team Treatment by OPUS team The OPUS trial The OPUS trial Results from two- and five-years follow- up Results from two- and five-years follow- up Conclusion Conclusion

4. 4

5. 5 The OPUS team Psychiatrist Psychiatrist Psychiatric nurse Psychiatric nurse Social worker Social worker Psychologist Occupational therapist Vocational guide

6. 6 Treatment by OPUS team Assertive Community Treatment Assertive Community Treatment Psychoeducational multi family groups Psychoeducational multi family groups Social skills training Social skills training

7. 7 Assertive Community Treatment Multidisciplinary team Multidisciplinary team Contact during in - and outpatient treatment Contact during in - and outpatient treatment Flexible frequency of contact (weekly) Flexible frequency of contact (weekly) Home visits Home visits Coordination of the GP, somatic Coordination of the GP, somatic department and social services

8. 8 Family Treatment Educational workshop for relatives. Educational workshop for relatives. Single family sessions with crisis intervention. Single family sessions with crisis intervention. McFarlanes model for psychoeducational multi­family groups. McFarlanes model for psychoeducational multi­family groups.

9. 9 Social skills training Coping with symptoms Coping with symptoms Managing own medication Managing own medication Basic social skill training Basic social skill training Problem solving Problem solving

10. 10 The OPUS trial Inclusion Criteria Age 18-45 Age 18-45 A diagnosis (ICD10 research criteria) of F2: schizophrenia, schizotypal disorder, delusional disorder, acute psychosis, schizoaffective psychosis or unspecific non-organic psychosis A diagnosis (ICD10 research criteria) of F2: schizophrenia, schizotypal disorder, delusional disorder, acute psychosis, schizoaffective psychosis or unspecific non-organic psychosis Patients have not had previously adequate treatment, defined as 12 weeks of anti- psychotic medication Patients have not had previously adequate treatment, defined as 12 weeks of anti- psychotic medication

11. 11 Assessments (1) SCAN (Schedule for Clinical Assessment in Neuropsychiatry) SCAN (Schedule for Clinical Assessment in Neuropsychiatry) SAPS (Schedule for Assessment of Positive Symptoms) SAPS (Schedule for Assessment of Positive Symptoms) SANS (Schedule for Assessment of Negative Symptoms) SANS (Schedule for Assessment of Negative Symptoms) Gaf (function and symptoms) Gaf (function and symptoms) Demographic data including educational, employment and housing status Demographic data including educational, employment and housing status Lancashire Quality of life Scale Lancashire Quality of life Scale Client Satisfaction Questionnaire Client Satisfaction Questionnaire Life Chart Schedule Life Chart Schedule Cognitive test (only at 5 years follow-up) Cognitive test (only at 5 years follow-up)

12. 12 Assessments (2) Complete case records from all mental health services in the catchment areas Complete case records from all mental health services in the catchment areas Danish Psychiatric Central Case Register Danish Psychiatric Central Case Register Cause of Death Register Cause of Death Register

13. 13 547 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 interviewed after five years (55%)

14. 14 547 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 after two years (62%) Attrition: 44 151 interviewed after five years (56%) 150 interviewed after five years (57%) Attrition: 80Attrition: 60 Base line 2 y 5 y Attrition: 26Attrition: 46

15. 15 Characteristics of 547 Patients, Baseline Age, years (mean)26.6 Age, years (mean)26.6 Male gender59 % Male gender59 % Diagnosis of schizophrenia 66 % Diagnosis of schizophrenia 66 % Secondary diagnosis substance abuse27% Secondary diagnosis substance abuse27% Duration of untreated psychosis 43 weeks median Duration of untreated psychosis 43 weeks median

16. 16 OPUS Standard Sign Out-patient contacts 1+2y, median75 20 <0.001 Family involved in treatment 1+2y61 % 20 % <0.001 Family psychoeducational gr. 1+2y46 % 2 % <0.001 Social skills training 1+2y43 % 12 % <0.001 Outpatient visits, family intervention and social skills training

17. 17 OPUS Standard Sign. ____________________________________________________ No out-patient visits,1y4 %15 % <0.001 No out-patient visits 2y7 %31 % <0.001 OR 0.2-0.3, NNT 4-8 Non-adherance

18. 18 Negative dimension Mean values at follow-up P<0.001 P=0.7

19. 19 Psychotic dimension Mean values at follow-up P=0.02 P= 0.31

20. 20 P = 0.03P=0.04 Harm and dependence Mean values at follow-up P=0.49

21. 21 Antipsychotic medication OPUS Standard Antipsych. med. 2 y 60 % 55 %Chi 2, 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

22. 22 Satisfaction with treatment 2 y

23. 23 Remission five years after debut - past two years OPUS team treatment N=151 Standard treatment N=150 Total Episodic21 (14%)24 (16%)45 (15%) Continous68 (45%)66 (44%)134 (44.5%) Not psychotic 62 (41%)60 (40%)122 (40.5%)

24. 24 Use of bed days from baseline – 5y OPUS Standard Sign. Mean days in hospital 951220.05 (baseline-2y) Mean days in hospital 59 710.34 (2y-5y) Mean days in hospital 154193 0.08 (baseline-5y)

25. 25 Cost-Benefit of OPUS Team- Treatment Mean of 39 bed days (20%) saved for patients in OPUS team treatment during five years Mean of 39 bed days (20%) saved for patients in OPUS team treatment during five years Saved cost of in-patient treatment for one year: Saved cost of in-patient treatment for one year: 7 million DKK for 100 patients ( 930000 euro) 7 million DKK for 100 patients ( 930000 euro) -more than enough to pay the wages of 10 staff members

26. 26 Use of bed days amongst patients with a secondary diagnosis of substance abuse P<0.05

27. 27 Independent housing baseline – 5 years OPUS Standard Sign. Not living independently (%) 7% 7% ns after 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

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

29. 29 OPUS; A sustainable treatment? Driving licence or painkiller Mette Bertelsen, Bispebjerg University Hospital, Denmark

30. 30 Conclusion (1) Significant reduction in symptoms after 2 years Significant reduction in symptoms after 2 years Significant reduction in drug- and alcohol misuse after 2 years Significant reduction in drug- and alcohol misuse after 2 years Significantly higher satisfaction with treatment Significantly higher satisfaction with treatment Low dose strategy succeeded Low dose strategy succeeded Better adherence to treatment Better adherence to treatment

31. 31 Conclusion (2) When patients were transferred to standard treatment after 2 years - no differerence between treatment groups with regard to; When patients were transferred to standard treatment after 2 years - no differerence between treatment groups with regard to; - negative symptoms - negative symptoms - psychotic symptoms - psychotic symptoms - harm and dependence - harm and dependence

32. 32 Conclusion (3) Number of bed days were reduced with a mean of 39 (20%) in OPUS team group compared with standard treatment after five years Number of bed days were reduced with a mean of 39 (20%) in OPUS team group compared with standard treatment after five years More patients from OPUS team live independently after 5 years More patients from OPUS team live independently after 5 years

33. 33 Clinical Implications Longer duration of treatment (3,4 or 5 years?) Longer duration of treatment (3,4 or 5 years?) Transition from OPUS treatment to standard treatment? Transition from OPUS treatment to standard treatment? Booster sessions? Booster sessions?

34. 34 The Danish OPUS Trial Funding: 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.

35. 35 The Danish OPUS Trial Merete Nordentoft Merete Nordentoft Pia Jeppesen Pia Jeppesen Maj-Britt Abel Maj-Britt Abel Anne Thorup Anne Thorup Lone Petersen Lone Petersen Johan Øhlenschlæger Johan Øhlenschlæger Runa Munkner Runa Munkner Mette Bertelsen Mette Bertelsen Ralf Hemmingsen Ralf Hemmingsen Per Jørgensen Torben Christensen Gertrud Krarup Phuong Le Quach Ole Mors Preben Bo Mortensen H:S, Bispebjerg and Sct Hans Hospital, University of Copenhagen Psychiatric Hospital, Risskov and Center for Registerbased Research University of Aarhus

36. 36 547 patienter inkluderet og randomiseret 272 patienter allokeret til standard behandling 205 interview efter to år (75%) Frafald: 62 4 selvmord 1 ukendt dødsårsag 1 død v. ulykke 33 afviste interview 9 flyttet langt væk 10 kunne ej spores 4 uvist 275 patienter allokeret til OPUS team 164 interview efter to år (62%) Frafald: 44 1 selvmord 21 afviste interview 10 flyttet langt væk 6 kunne ej spores 6 uvist 151 interview efter fem år (56%) 150 interview efter fem år (57%) Frafald: 80 2 selvmord 2 ukendt dødsårsag 1 død v. ulykke 48 afviste interview 1 flyttet langt væk 26 kunne ej spores Frafald: 60 1 naturlig dødsårsag 3 ukendt dødsårsag 32 afviste interview 5 flyttet langt væk 19 kunne ej spores Base line 2 y 5 y Frafald: 26 13 afviste int. 4 flyttet 6 ej spores 3 uvist Frafald 46 22 afviste int. 7 flyttet 12 ej spores 5 uvist