Effect of ω-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk for Psychotic Disorders: The NEURAPRO Randomized Clinical Trial

Patrick D McGorry; Barnaby Nelson; Connie Markulev; Hok Pan Yuen; Miriam R Schäfer; Nilufar Mossaheb; Monika Schlögelhofer; Stephan Smesny; Ian B Hickie; Gregor Emanuel Berger; Eric Y H Chen; Lieuwe de Haan; Dorien H Nieman; Merete Nordentoft; Anita Riecher-Rössler; Swapna Verma; Andrew Thompson; Alison Ruth Yung; G Paul Amminger

doi:10.1001/jamapsychiatry.2016.2902

Effect of ω-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk for Psychotic Disorders: The NEURAPRO Randomized Clinical Trial

Patrick D McGorry, Barnaby Nelson, Connie Markulev, Hok Pan Yuen, Miriam R Schäfer, Nilufar Mossaheb, Monika Schlögelhofer, Stephan Smesny, Ian B Hickie, Gregor Emanuel Berger, Eric Y H Chen, Lieuwe de Haan, Dorien H Nieman, Merete Nordentoft, Anita Riecher-Rössler, Swapna Verma, Andrew Thompson, Alison Ruth Yung, G Paul Amminger

Department of Clinical Medicine

132 Citations (Scopus)

Abstract

IMPORTANCE :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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.

Original language	English
Journal	JAMA Psychiatry
Volume	74
Issue number	1
Pages (from-to)	19-27
Number of pages	9
ISSN	2168-622X
DOIs	https://doi.org/10.1001/jamapsychiatry.2016.2902
Publication status	Published - 1 Jan 2017

Keywords

Adolescent
Adult
Case Management
Cognitive Therapy
Cohort Studies
Combined Modality Therapy
Dietary Supplements/adverse effects
Disease Progression
Double-Blind Method
Early Medical Intervention
Fatty Acids, Omega-3/administration & dosage
Female
Humans
Male
Psychotic Disorders/drug therapy
Risk
Young Adult

Access to Document

10.1001/jamapsychiatry.2016.2902

Cite this

McGorry, P. D., Nelson, B., Markulev, C., Yuen, H. P., Schäfer, M. R., Mossaheb, N., Schlögelhofer, M., Smesny, S., Hickie, I. B., Berger, G. E., Chen, E. Y. H., de Haan, L., Nieman, D. H., Nordentoft, M., Riecher-Rössler, A., Verma, S., Thompson, A., Yung, A. R., & Amminger, G. P. (2017). Effect of ω-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk for Psychotic Disorders: The NEURAPRO Randomized Clinical Trial. JAMA Psychiatry, 74(1), 19-27. https://doi.org/10.1001/jamapsychiatry.2016.2902

McGorry, PD, Nelson, B, Markulev, C, Yuen, HP, Schäfer, MR, Mossaheb, N, Schlögelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rössler, A, Verma, S, Thompson, A, Yung, AR & Amminger, GP 2017, 'Effect of ω-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk for Psychotic Disorders: The NEURAPRO Randomized Clinical Trial', JAMA Psychiatry, vol. 74, no. 1, pp. 19-27. https://doi.org/10.1001/jamapsychiatry.2016.2902

@article{05af842b169746dc9417f7af76b79ecb,

title = "Effect of ω-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk for Psychotic Disorders: The NEURAPRO Randomized Clinical Trial",

abstract = "IMPORTANCE :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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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-{\AA}sberg 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 AND RELEVANCE: 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.",

keywords = "Adolescent, Adult, Case Management, Cognitive Therapy, Cohort Studies, Combined Modality Therapy, Dietary Supplements/adverse effects, Disease Progression, Double-Blind Method, Early Medical Intervention, Fatty Acids, Omega-3/administration & dosage, Female, Humans, Male, Psychotic Disorders/drug therapy, Risk, Young Adult",

author = "McGorry, {Patrick D} and Barnaby Nelson and Connie Markulev and Yuen, {Hok Pan} and Sch{\"a}fer, {Miriam R} and Nilufar Mossaheb and Monika Schl{\"o}gelhofer and Stephan Smesny and Hickie, {Ian B} and Berger, {Gregor Emanuel} and Chen, {Eric Y H} and {de Haan}, Lieuwe and Nieman, {Dorien H} and Merete Nordentoft and Anita Riecher-R{\"o}ssler and Swapna Verma and Andrew Thompson and Yung, {Alison Ruth} and Amminger, {G Paul}",

year = "2017",

month = jan,

day = "1",

doi = "10.1001/jamapsychiatry.2016.2902",

language = "English",

volume = "74",

pages = "19--27",

journal = "JAMA Psychiatry",

issn = "2168-622X",

publisher = "The JAMA Network",

number = "1",

}

TY - JOUR

T1 - Effect of ω-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk for Psychotic Disorders

T2 - The NEURAPRO Randomized Clinical Trial

AU - McGorry, Patrick D

AU - Nelson, Barnaby

AU - Markulev, Connie

AU - Yuen, Hok Pan

AU - Schäfer, Miriam R

AU - Mossaheb, Nilufar

AU - Schlögelhofer, Monika

AU - Smesny, Stephan

AU - Hickie, Ian B

AU - Berger, Gregor Emanuel

AU - Chen, Eric Y H

AU - de Haan, Lieuwe

AU - Nieman, Dorien H

AU - Nordentoft, Merete

AU - Riecher-Rössler, Anita

AU - Verma, Swapna

AU - Thompson, Andrew

AU - Yung, Alison Ruth

AU - Amminger, G Paul

PY - 2017/1/1

Y1 - 2017/1/1

N2 - IMPORTANCE :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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.

AB - IMPORTANCE :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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.

KW - Adolescent

KW - Adult

KW - Case Management

KW - Cognitive Therapy

KW - Cohort Studies

KW - Combined Modality Therapy

KW - Dietary Supplements/adverse effects

KW - Disease Progression

KW - Double-Blind Method

KW - Early Medical Intervention

KW - Fatty Acids, Omega-3/administration & dosage

KW - Female

KW - Humans

KW - Male

KW - Psychotic Disorders/drug therapy

KW - Risk

KW - Young Adult

U2 - 10.1001/jamapsychiatry.2016.2902

DO - 10.1001/jamapsychiatry.2016.2902

M3 - Journal article

C2 - 27893018

SN - 2168-622X

VL - 74

SP - 19

EP - 27

JO - JAMA Psychiatry

JF - JAMA Psychiatry

IS - 1

ER -

Effect of ω-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk for Psychotic Disorders: The NEURAPRO Randomized Clinical Trial

Abstract

Keywords

Access to Document

Fingerprint

Cite this