title: Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: twelve-month outcome.
abstract: OBJECTIVE
  The ultra-high risk clinical phenotype is associated with substantial distress and functional impairment and confers a greatly enhanced risk for transition to full-threshold psychosis. A range of interventions aimed at relieving current symptoms and functional impairment and reducing the risk of transition to psychosis has shown promising results, but the optimal type and sequence of intervention remain to be established. The aim of this study was to determine which intervention was most effective at preventing transition to psychosis: cognitive therapy plus low-dose risperidone, cognitive therapy plus placebo, or supportive therapy plus placebo.
  
  
  METHODS
  A double-blind, randomized, placebo-controlled 12-month trial of low-dose risperidone, cognitive therapy, or supportive therapy was conducted in a cohort of 115 clients of the Personal Assessment and Crisis Evaluation Clinic, a specialized service for young people at ultra-high risk of psychosis located in Melbourne, Australia. Recruitment commenced in August 2000 and ended in May 2006. The primary outcome measure was transition to full-threshold psychosis, defined a priori as frank psychotic symptoms occurring at least daily for 1 week or more and assessed using the Comprehensive Assessment of At-Risk Mental States. Secondary outcome measures were psychiatric symptoms, psychosocial functioning, and quality of life.
  
  
  RESULTS
  The estimated 12-month transition rates were as follows: cognitive therapy + risperidone, 10.7%; cognitive therapy + placebo, 9.6%; and supportive therapy + placebo, 21.8%. While there were no statistically significant differences between the 3 groups in transition rates (log-rank test P = .60), all 3 groups improved substantially during the trial, particularly in terms of negative symptoms and overall functioning.
  
  
  CONCLUSIONS
  The lower than expected, essentially equivalent transition rates in all 3 groups fail to provide support for the first-line use of antipsychotic medications in patients at ultra-high risk of psychosis, and an initial approach with supportive therapy is likely to be effective and carries fewer risks.
authors.affiliation: Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia. pmcgorry@unimelb.edu.au
authors.forename: Patrick D
authors.initials: PD
authors.lastname: McGorry
authors.forename: Barnaby
authors.initials: B
authors.lastname: Nelson
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Phillips
authors.forename: Hok Pan
authors.initials: HP
authors.lastname: Yuen
authors.forename: Shona M
authors.initials: SM
authors.lastname: Francey
authors.forename: Annette
authors.initials: A
authors.lastname: Thampi
authors.forename: Gregor E
authors.initials: GE
authors.lastname: Berger
authors.forename: G Paul
authors.initials: GP
authors.lastname: Amminger
authors.forename: Magenta B
authors.initials: MB
authors.lastname: Simmons
authors.forename: Daniel
authors.initials: D
authors.lastname: Kelly
authors.forename: Grad
authors.initials: G
authors.lastname: Dip
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Thompson
authors.forename: Alison R
authors.initials: AR
authors.lastname: Yung
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011613:Psychotherapy / Q000379:methods*; D011618:Psychotic Disorders / Q000517:prevention & control*; D012306:Risk; D018967:Risperidone / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone