title: 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: 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.
  
  
  
  Randomised, superiority, parallel group trial with blinded outcome assessment. Randomisation was centralised and computerised with concealed randomisation sequence carried out at an external site.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Copenhagen University Hospital, Mental Health Centre Copenhagen, Research Unit, Hellerup, Denmark Nikolai.albert@regionh.dk.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Albert
authors.affiliation: Copenhagen University Hospital, Mental Health Centre Copenhagen, Research Unit, Hellerup, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Melau
authors.affiliation: Copenhagen University Hospital, Mental Health Centre Copenhagen, Research Unit, Hellerup, Denmark.
authors.forename: Heidi
authors.initials: H
authors.lastname: Jensen
authors.affiliation: Psychosis Ward, Section P, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Emborg
authors.affiliation: Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Glostrup, Denmark.
authors.forename: Jens Richardt Mollegaard
authors.initials: JR
authors.lastname: Jepsen
authors.affiliation: Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Glostrup, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Fagerlund
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.affiliation: Psychosis Research Unit, Aarhus University Hospital, Risskov, Risskov, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.affiliation: Copenhagen University Hospital, Mental Health Centre Copenhagen, Research Unit, Hellerup, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Hjorthøj
authors.affiliation: Copenhagen University Hospital, Mental Health Centre Copenhagen, Research Unit, Hellerup, Denmark.
authors.forename: Merete
authors.initials: M
authors.lastname: Nordentoft
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001521:Behavior Therapy; D003156:Community Mental Health Services; D003718:Denmark; D061345:Early Medical Intervention; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000188:drug therapy / Q000628:therapy*; D066107:Social Skills; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents