Long-Chain ω-3 Fatty Acids for Indicated Prevention of Psychotic Disorders: A Randomized, Placebo-Controlled Trial

Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria.
Archives of general psychiatry (Impact Factor: 14.48). 02/2010; 67(2):146-54. DOI: 10.1001/archgenpsychiatry.2009.192
Source: PubMed


The use of antipsychotic medication for the prevention of psychotic disorders is controversial. Long-chain omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) may be beneficial in a range of psychiatric conditions, including schizophrenia. Given that omega-3 PUFAs are generally beneficial to health and without clinically relevant adverse effects, their preventive use in psychosis merits investigation.
To determine whether omega-3 PUFAs reduce the rate of progression to first-episode psychotic disorder in adolescents and young adults aged 13 to 25 years with subthreshold psychosis.
Randomized, double-blind, placebo-controlled trial conducted between 2004 and 2007.
Psychosis detection unit of a large public hospital in Vienna, Austria.
Eighty-one individuals at ultra-high risk of psychotic disorder.
A 12-week intervention period of 1.2-g/d omega-3 PUFA or placebo was followed by a 40-week monitoring period; the total study period was 12 months.
The primary outcome measure was transition to psychotic disorder. Secondary outcomes included symptomatic and functional changes. The ratio of omega-6 to omega-3 fatty acids in erythrocytes was used to index pretreatment vs posttreatment fatty acid composition.
Seventy-six of 81 participants (93.8%) completed the intervention. By study's end (12 months), 2 of 41 individuals (4.9%) in the omega-3 group and 11 of 40 (27.5%) in the placebo group had transitioned to psychotic disorder (P = .007). The difference between the groups in the cumulative risk of progression to full-threshold psychosis was 22.6% (95% confidence interval, 4.8-40.4). omega-3 Polyunsaturated fatty acids also significantly reduced positive symptoms (P = .01), negative symptoms (P = .02), and general symptoms (P = .01) and improved functioning (P = .002) compared with placebo. The incidence of adverse effects did not differ between the treatment groups.
Long-chain omega-3 PUFAs reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states. Trial Registration clinicaltrials.gov Identifier: NCT00396643.

Download full-text


Available from: Sue Maree Cotton,
  • Source
    • "As any treatment seems to delay or prevent psychosis onset (van der Gaag et al., 2013), this low medication rate might have further contributed to both the high rate of BIPS and conversions. (3) A certain strength is the absence of any refusals to participate or drop-outs, while (4) the small sample size is a certain limitation similar to previous studies (Amminger et al., 2010; Fux et al., 2013; Lindgren et al., 2014; Welsh and Tiffin, 2014) which prevented a more detailed analysis of clinical outcomes. However, our analyses uniquely distinguished between APS-and BIPS-level risk symptoms, thereby giving new indications towards possible developmental peculiarities of UHR states in CAD. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The validity of current ultra-high risk (UHR) criteria is under-examined in help-seeking minors, particularly, in children below the age of 12years. Thus, the present study investigated predictors of one-year outcome in children and adolescents (CAD) with UHR status. Method: Thirty-five children and adolescents (age 9-17years) meeting UHR criteria according to the Structured Interview for Psychosis-Risk Syndromes were followed-up for 12months. Regression analyses were employed to detect baseline predictors of conversion to psychosis and of outcome of non-converters (remission and persistence of UHR versus conversion). Results: At one-year follow-up, 20% of patients had developed schizophrenia, 25.7% had remitted from their UHR status that, consequently, had persisted in 54.3%. No patient had fully remitted from mental disorders, even if UHR status was not maintained. Conversion was best predicted by any transient psychotic symptom and a disorganized communication score. No prediction model for outcome beyond conversion was identified. Conclusions: Our findings provide the first evidence for the predictive utility of UHR criteria in CAD in terms of brief intermittent psychotic symptoms (BIPS) when accompanied by signs of cognitive impairment, i.e. disorganized communication. However, because attenuated psychotic symptoms (APS) related to thought content and perception were indicative of non-conversion at 1-year follow-up, their use in early detection of psychosis in CAD needs further study. Overall, the need for more in-depth studies into developmental peculiarities in the early detection and treatment of psychoses with an onset of illness in childhood and early adolescence was further highlighted.
    Schizophrenia Research 11/2015; DOI:10.1016/j.schres.2015.10.033 · 3.92 Impact Factor
    • "The study was initially conducted in 81 help-seeking UHR individuals , aged between 13 and 25 years, and meeting one or more of the well-defined and validated " ultra-high risk " (UHR) criteria [51] [52] [53] [54]. For further information on study inclusion and exclusion criteria see Supplementary material and Amminger et al. [44]. While baseline blood samples were available in 73/81 individuals , follow-up erythrocyte samples were collected in 64/81 individuals (for demographic information and transition vs. nontransition status see Table 1). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Oxidative stress and impaired antioxidant defenses are reported in schizophrenia and are associated with disturbed neurodevelopment, brain structural alterations, glutamatergic imbalance, increased negative symptoms, and cognitive impairment. There is evidence that oxidative stress predates the onset of acute psychotic illness. Here, we investigate the effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system (AODS). In 64 help-seeking UHR-individuals (13-25 years of age), vitamin E levels and glutathione were investigated before and after 12 weeks of treatment with either 1.2g/d omega-3 (PUFA-E) or saturated fatty acids (SFA-E), with each condition also containing 30.4mg/d alpha-tocopherol to ensure absorption without additional oxidative risk. In multivariate tests, the effects on the AODS (alpha-tocopherol, total glutathione) were not significantly different (p=0.13, p=0.11, respectively) between treatment conditions. According to univariate findings, only PUFA-E caused a significant alpha-tocopherol increase, while PUFA-E and SFA-E caused a significant gamma- and delta-tocopherol decrease. Total glutathione (GSHt) was decreased by PUFA-E supplementation. Effects of the PUFA-E condition on the vitamin E and glutathione AODS could be mechanisms underlying its clinical effectiveness. In terms of the vitamin E protection system, PUFA-E seems to directly support the antioxidative defense at membrane level. The effect of PUFA-E on GSHt is not yet fully understood, but could reflect antioxidative effects, resulting in decreased demand for glutathione. It is still necessary to further clarify which type of PUFA/antioxidant combination, and in which dose, is effective at each stage of psychotic illness. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Prostaglandins Leukotrienes and Essential Fatty Acids 07/2015; 101. DOI:10.1016/j.plefa.2015.07.001 · 2.35 Impact Factor
  • Source
    • "and perospirone [113] using an uncontrolled design, and, as RCTs, olanzapine versus placebo [63], 'risperidone plus CBT' versus need-based intervention (NBI) [68], 'amisulpride plus NBI' versus NBI [94], and 'risperidone plus CBT' versus 'placebo plus supportive therapy' [69]. Only one included pharmacological study did not use antipsychotic medication but a neuroprotective approach, and investigated the effect of omega-3 polyunsaturated fatty acids (PUFAS) in CHR patients compared to placebo in a RCT [4]. Side effects of each pharmacological trial are listed in Table 1. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This guidance paper from the European Psychiatric Association (EPA) aims to provide evidence-based recommendations on early intervention in clinical high risk (CHR) states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. Besides analyses on treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n=1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates, but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples could have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Psychiatry 03/2015; 30:388-404. DOI:10.1016/j.eurpsy.2015.01.013 · 3.44 Impact Factor
Show more