title: Effect of ω-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk for Psychotic Disorders: The NEURAPRO Randomized Clinical Trial.
abstract: OBJECTIVE
  A promising treatment to prevent onset and improve outcomes in patients at ultrahigh risk for psychosis is dietary supplementation with long-chain ω-3 polyunsaturated fatty acids (PUFAs).
  
  
  OBJECTIVE
  To determine whether treatment with ω-3 PUFAs in combination with a high-quality psychosocial intervention (cognitive behavioral case management [CBCM]) is more effective than placebo plus CBCM.
  
  
  METHODS
  NEURAPRO, a double-blind, placebo-controlled, randomized clinical trial, was conducted from March 1, 2010, to September 30, 2014, in 10 specialized early psychosis treatment services in Australia, Asia, and Europe. The primary analysis used the intention-to-treat approach.
  
  
  METHODS
  A daily dose of 1.4 g of ω-3 PUFAs or placebo (paraffin oil), plus 20 or fewer sessions of CBCM over the 6-month study period.
  
  
  METHODS
  The primary outcome was transition to psychosis status at 6 months. The secondary outcomes were general levels of psychopathology and functioning, as assessed by the Brief Psychiatric Rating Scale (BPRS) (range, 24-168), Scale for the Assessment of Negative Symptoms (SANS) (range, 0-125), Montgomery-Åsberg Depression Rating Scale (MADRS) (range, 0-60), Young Mania Rating Scale (YMRS) (range, 0-44), Social and Occupational Functioning Assessment Scale (SOFAS) (range, 0-100), and the Global Functioning: Social and Role scale (range, 0-10). For SOFAS and Global Functioning: Social and Role scale, higher scores were better; for other measures, lower scores were better.
  
  
  RESULTS
  In this study of 304 adults at ultrahigh risk for psychotic disorders, 153 (50.3%) received ω-3 PUFAs and 151 (49.7%) received placebo. In all, 139 (45.7%) were male; mean (SD) age was 19.1 (4.6) years. The Kaplan-Meier-estimated 6-month transition rates were 5.1% (95% CI, 1.3%-8.7%) in the control group and 6.7% (95% CI, 2.3%-10.8%) in the ω-3 PUFA group. At 12 months, the rates were 11.2% (95% CI, 5.5%-16.7%) in the control group and 11.5% (95% CI, 5.8%-16.9%) in the ω-3 PUFA group. No significant difference was observed between the transition rates of both groups (hazard ratio, 1.1; 95% CI, 0.55-2.23; P = .76, stratified log-rank test).
  
  
  CONCLUSIONS
  This trial clearly failed to replicate the findings of the original single-center trial. The most likely explanation is that ω-3 PUFAs lack efficacy under these conditions. However, the lower-than-expected transition rate may have prevented a test of the main hypothesis. Given the substantial symptomatic and functional improvement in both groups, the other treatments received (ie, CBCM and antidepressants) likely produced a ceiling effect beyond which ω-3 PUFAs, even if effective, could not be shown to confer additional benefits. Nevertheless, the main conclusion is that ω-3 PUFAs are not effective under conditions where good quality, evidence-based psychosocial treatment is available.
  
  
  BACKGROUND
  anzctr.org.au Identifier: 12608000475347.
authors.affiliation: Orygen, National Centre of Excellence in Youth Mental Health, Melbourne, Australia2Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: McGorry
authors.affiliation: Orygen, National Centre of Excellence in Youth Mental Health, Melbourne, Australia2Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia.
authors.forename: Barnaby
authors.initials: B
authors.lastname: Nelson
authors.affiliation: Orygen, National Centre of Excellence in Youth Mental Health, Melbourne, Australia2Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia.
authors.forename: Connie
authors.initials: C
authors.lastname: Markulev
authors.affiliation: Orygen, National Centre of Excellence in Youth Mental Health, Melbourne, Australia2Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia.
authors.forename: Hok Pan
authors.initials: HP
authors.lastname: Yuen
authors.affiliation: Orygen, National Centre of Excellence in Youth Mental Health, Melbourne, Australia3Department of Psychiatry, Medical University of Vienna, Vienna, Austria.
authors.forename: Miriam R
authors.initials: MR
authors.lastname: Schäfer
authors.affiliation: Department of Psychiatry, Medical University of Vienna, Vienna, Austria.
authors.forename: Nilufar
authors.initials: N
authors.lastname: Mossaheb
authors.affiliation: Department of Psychiatry, Medical University of Vienna, Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Schlögelhofer
authors.affiliation: Department of Psychiatry, University Hospital, Jena, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Smesny
authors.affiliation: Brain and Mind Research Institute, University of Sydney, Sydney, Australia.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Hickie
authors.affiliation: Child and Adolescent Psychiatric Service of the Canton of Zurich, Zurich, Switzerland.
authors.forename: Gregor Emanuel
authors.initials: GE
authors.lastname: Berger
authors.affiliation: Department of Psychiatry, University of Hong Kong, Hong Kong.
authors.forename: Eric Y H
authors.initials: EY
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Lieuwe
authors.initials: L
authors.lastname: de Haan
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Dorien H
authors.initials: DH
authors.lastname: Nieman
authors.affiliation: Psychiatric Centre Bispebjerg, Copenhagen, Denmark.
authors.forename: Merete
authors.initials: M
authors.lastname: Nordentoft
authors.affiliation: Psychiatric University Clinics Basel, Basel, Switzerland.
authors.forename: Anita
authors.initials: A
authors.lastname: Riecher-Rössler
authors.affiliation: Institute of Mental Health, Singapore, Singapore.
authors.forename: Swapna
authors.initials: S
authors.lastname: Verma
authors.affiliation: Orygen, National Centre of Excellence in Youth Mental Health, Melbourne, Australia12Division of Mental Health and Wellbeing, Warwick Medical School, University of Warwick, Coventry, England13North Warwickshire Early Intervention in Psychosis Service, Coventry and Warwickshire National Health Service Partnership Trust, Coventry, England.
authors.forename: Andrew
authors.initials: A
authors.lastname: Thompson
authors.affiliation: Orygen, National Centre of Excellence in Youth Mental Health, Melbourne, Australia14Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, England15Greater Manchester West National Health Service Mental Health Foundation Trust, Manchester, England.
authors.forename: Alison Ruth
authors.initials: AR
authors.lastname: Yung
authors.affiliation: Orygen, National Centre of Excellence in Youth Mental Health, Melbourne, Australia2Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia3Department of Psychiatry, Medical University of Vienna, Vienna, Austria.
authors.forename: G Paul
authors.initials: GP
authors.lastname: Amminger
mesh_terms: D000293:Adolescent; D000328:Adult; D019090:Case Management; D015928:Cognitive Behavioral Therapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D019587:Dietary Supplements / Q000009:adverse effects*; D018450:Disease Progression; D004311:Double-Blind Method; D061345:Early Medical Intervention; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D011618:Psychotic Disorders / Q000188:drug therapy*; D012306:Risk; D055815:Young Adult
chemical_list: D015525:Fatty Acids, Omega-3