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

ABSTRACT 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 Identifier: NCT00396643.

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Available from: Sue Maree Cotton, Sep 27, 2015
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    • "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). "
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    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
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    • "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. "
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    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
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    • "Two RCTs compared risperidone and CBT over supportive counselling (McGorry et al. 2002; Phillips et al. 2009). Other RCTs compared risperidone and CBT v. placebo and CBT (Phillips et al. 2009), olanzapine v. placebo (McGlashan et al. 2003), integrated therapies over supportive counselling (Bechdolf et al. 2012), integrated therapies over standard treatment (Nordentoft et al. 2006), omega-3 fatty acids v. placebo (Amminger et al. 2010), and amisulpride plus a needs-based intervention v. the needs-based intervention alone (Ruhrmann et al. 2007). Overall, five out of 11 RCTs showed a moderate effect of CBT on preventing transition to psychosis (relative risk at 12 months = 0.54) (Stafford et al. 2013), and this finding has been validated by a second independent meta-analysis focused on CBT (relative risk at 12 months = 0.45) (Hutton & Taylor, 2014). "
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    ABSTRACT: Background: Recent randomized controlled trials suggest some efficacy for focused interventions in subjects at high risk (HR) for psychosis. However, treating HR subjects within the real-world setting of prodromal services is hindered by several practical problems that can significantly make an impact on the effect of focused interventions. Method: All subjects referred to Outreach and Support in South London (OASIS) and diagnosed with a HR state in the period 2001-2012 were included (n = 258). Exposure to focused interventions was correlated with sociodemographic and clinical characteristics at baseline. Their association with longitudinal clinical and functional outcomes was addressed at follow-up. Results: In a mean follow-up time of 6 years (s.d. = 2.5 years) a transition risk of 18% was observed. Of the sample, 33% were treated with cognitive behavioural therapy (CBT) only; 17% of subjects received antipsychotics (APs) in addition to CBT sessions. Another 17% of subjects were prescribed with antidepressants (ADs) in addition to CBT. Of the sample, 20% were exposed to a combination of interventions. Focused interventions had a significant relationship with transition to psychosis. The CBT + AD intervention was associated with a reduced risk of transition to psychosis, as compared with the CBT + AP intervention (hazards ratio = 0.129, 95% confidence interval 0.030-0.565, p = 0.007). Conclusions: There were differential associations with transition outcome for AD v. AP interventions in addition to CBT in HR subjects. These effects were not secondary to baseline differences in symptom severity.
    Psychological Medicine 10/2014; 45(06):1-13. DOI:10.1017/S003329171400244X · 5.94 Impact Factor
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