Five years of specialised early intervention versus two years of specialised early intervention followed by three years of standard treatment for patients with a first episode psychosis: randomised, superiority, parallel group trial in Denmark (OPUS II)

Abstract

Objective To compare the effects of five years of specialised early intervention (SEI) treatment for first episode schizophrenia spectrum disorder with the standard two years of SEI plus three years of treatment as usual.Design Randomised, superiority, parallel group trial with blinded outcome assessment. Randomisation was centralised and computerised with concealed randomisation sequence carried out at an external site.Setting Participants were recruited from six OPUS teams in Denmark between 2009 and 2012. OPUS teams provide SEI treatment to all patients diagnosed with a schizophrenia spectrum disorder in Denmark.Participants 400 participants (51% women) with a mean age of 25.6 (standard deviation 4.3) were randomised to five years of SEI (experimental intervention; n=197) or to two years of SEI plus three years of treatment as usual (control; n=203).Interventions OPUS treatment consists of three core elements—modified assertive community treatment, family involvement, and social skill training—with a patient-case manager ratio of no more than 12:1. For participants randomised to five years of OPUS treatment, the treatment was largely unchanged. Participants randomised to the control group were mostly referred to community health centres after two years of SEI treatment.Main outcomes Follow-up assessments were conducted five years after start of OPUS treatment. Primary outcome was negative symptoms measured on the scale for assessment of negative symptoms (avolition-apathy, anhedonia, alogia, and affective blunting). Secondary outcomes were remission of both negative and psychotic symptoms, psychotic symptoms, suicidal ideation, substance abuse, compliance with medical treatment, adherence with treatment, client satisfaction, days in hospital care, and labour market affiliation.Results Levels of negative symptoms did not differ between the intervention group and control group (1.72 v 1.81 points; estimated mean difference −0.10 (95% confidence interval 0.33 to 0.13), P=0.39). Participants receiving five years of OPUS treatment were more likely to remain in contact with specialised mental health services (90.4% v 55.6%, P<0.001), had higher client satisfaction (estimated mean difference 2.57 points (95% confidence interval 1.36 to 3.79), P<0.001), and had a stronger working alliance (estimated mean difference 5.56 points (95% confidence interval 2.30 to 8.82), P=0.001) than the control group.Conclusions This trial tests SEI treatment for up to five years for patients with first episode schizophrenia spectrum disorder; previous trials have found treatment effects for programmes lasting from one to three years. The prolonged SEI treatment had few effects, which could be due to the high level of treatment provided to control participants and the late start of specialised treatment.Trial registration Clinicaltrial.gov NCT00914238.

Description, evaluation and scale‐up potential of a model for rapid access to early intervention for psychosis

“…At PEPP, the median DUP for all accepted patients is 114 days/16.35 weeks (range: 0-512 days). This is significantly shorter than the DUPs of 6 to 12 months, or more, that many other early intervention services report (Albert et al, 2017;Lloyd-Evans et al, 2011;Marshall et al, 2005). PEPP's median referral delay is 1.28 weeks (range: −13.2 to 445 weeks).…”

Comparing three‐year extension of early intervention service to regular care following two years of early intervention service in first‐episode psychosis: a randomized single blind clinical trial

“…The most recent trial from the OPUS program in Denmark has reported the absence of any significant differences in the level of negative symptoms between a three-year extension of early intervention service and regular care following two years of early intervention service 18 . The differences in the results of our study and the new OPUS study can be explained at several levels.…”

Short duration of untreated psychosis enhances negative symptom remission in extended early intervention service for psychosis

“…While these successes have enabled the scaling up of EIS to regional and national levels , there has been far less attention to the essential task of reducing DUP . Indeed, a majority of EIS across multiple jurisdictions (United Kingdom, Denmark and United States of America) continue to report very long DUP .…”