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Omega-3s Curb Psychosis in Clinical Trial
2/4/2010
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Preliminary findings dovetail with prior indications and should encourage further research
by Craig Weatherby


The average age at which symptoms of psychosis appear is only 25... a tragically early beginning to a terrible affliction.

Now, Austrian researchers say they’ve published the first clinical trial to show benefits of omega-3 fatty acids in younger people at “ultra-high” risk of psychosis.

The results led the authors to pen a pretty clear conclusion:

“Long-chain omega-3s reduce the risk of progression to psychotic disorder… in young people with sub-threshold psychotic states… omega-3s may offer a viable prevention and treatment strategy...” (Amminger GP et al. 2009).

This is not a case of choosing between drugs or omega-3s.

More research is needed to prove the efficacy of omega-3s, which might be prescribed as a complement to anti-psychotic drugs... one that might permit lowering the dose of such drugs.

Those who’ve worked with people taking anti-psychotics
this writer includedknow that they they’re often preferable only to the agonies that psychosis inflicts on patients and their families.

So it seems significant that the authors of the new trial noted some key advantages of omega-3s versus standard anti-psychotic drugs:

“Adverse effects
which include metabolic changes, sexual dysfunction and weight gainassociated with the use of anti-psychotics are often not acceptable for young people. [In contrast, omega-3s]… have the advantage of excellent tolerability, public acceptance, relatively low costs and benefits for general health” (Amminger GP et al. 2009).

Another serious side effect of anti-psychotic medications is the movement disorder called tardive dyskinesia (TD), which can be disabling and disfiguring. About 15 percent of patients taking anti-psychotic drugs develop TD within three years.

Early detection of TD symptoms is critical in reducing the severity of this often-irreversible disorder… but psychotic patients who develop drug-induced tardive dyskinesia rarely identify early warning signs because the involuntary movements do not cause physical discomfort.

What the study showed
Dr. G. Paul Amminger and his colleagues at the Medical University of Vienna recruited 76 people aged 13 to 25 who’d been diagnosed at very high risk of progressing to full-blown psychosis.

High risk was defined as having mild psychotic symptoms, transient psychosis, or a family history of psychotic disorders, combined with a decline in daily functioning.

The chance that someone meeting these criteria will become seriously psychotic within one year is as high as four in 10.

The researchers randomly assigned the volunteers to receive a daily placebo (coconut oil) capsules or supplements of fish oil containing 1.2 grams of omega-3s, including 700 mg of EPA and 480 mg of DHA.

The participants took the supplements or placebo for 12 weeks, and were followed for one year.

After 12 months, only 4.9 percent of the omega-3 group (two out of 41) had progressed to full-blown psychotic disorder, compared with 27.5 percent (11 of 40) in the placebo group.

In other words, compared to placebo, supplementation with fish oil appeared to reduce the risk that at-risk youths would progress to “full threshold psychosis” within a year by one-fifth to one-quarter (22.6 percent).

The Austrians expressed optimism, writing, “The finding that […] a natural substance may prevent or at least delay the onset of psychotic disorder gives hope that there may be alternatives to anti-psychotic [drugs] for the prodromal [early symptomatic] phase.” (Amminger GP et al. 2009

One has to wonder what the risk reduction rates might be if at-risk youths were prescribed omega-3 fish oil much earlier in life, as a preventive measure.

Actually, the first clinical evidence that omega-3s may play a role in psychosisat least the form called schizophreniadates back at least 14 years, when the authors of an evidence review made this report:

“schizophrenic patients who eat more omega-3 fatty acids in their normal diet have less severe symptoms. In a pilot study of omega-3 fatty acid supplementation we observed significant improvement in both schizophrenic symptoms and tardive dyskinesia over a 6 week period” (Peet M et al. 1996).

Could omega-3s help: If so, how?
Back in 2002, the Canadian authors of a study commissioned by the U.S. Agency for Healthcare Research and Quality cited evidence that points toward real promise, and urged more research:

“Nothing can yet be concluded concerning the clinical utility of omega-3 fatty acids as supplemental treatment for any other psychiatric disorder or condition, or as a primary treatment for all psychiatric disorders or conditions, examined in our review. Much more research, implementing design and methods improvements, is needed...” (Schachter HM et al. 2005).

And they made note that the extremely unbalanced intakes of omega-6 (too many) and omega-3 (too few) fats in most Americans’ diets might underlie some psychiatric disorders:

“If a reasonable view is that omega-3 fatty acids may play a role in mental health, then given the… inter-relationships between omega-3 and omega-6 fatty acid[s]… it may behoove researchers to investigate the possible therapeutic or preventive value of [changing] the dietary omega-6/omega-3 fatty acid intake ratio” (Schachter HM et al. 2005).

Prior research shows that schizophrenic patients and first-episode psychosis patients have significantly lower levels of omega-3 DHA in their brain cell membranes, compared with healthy people or chronic psychotics, respectively (Khan MM et al 2002; Mahadik SP et al.1994).

And the Austrian researchers noted that omega-3s may produce changes in cell membranes and interactions with neurotransmitter systems in the brain.

Indeed, Australian researchers who examined patients’ brains using MRI machines reported that supplements of omega-3 EPA from fish oil produced significant, beneficial changes in the brain cells of young people who’d recently had their first episode of psychosis (Berger GE et al 2008).

These beneficial changes included increases in levels of a key internal antioxidant (glutathione) and a key neurotransmitter (glutamate)… changes that correlated with symptomatic improvements.

As the Australian team wrote, “some of the metabolic brain changes… correlated with negative symptom improvement. Larger confirmatory studies… are warranted” (Berger GE et al 2008).

Is anyone listening at NIH or in Congress?

We hope that the wide reporting of these new findings lead to funding for more research!


Sources
  • Amminger GP, Schäfer MR, Papageorgiou K, Klier CM, Cotton SM, Harrigan SM, Mackinnon A, McGorry PD, Berger GE. Long-Chain {omega}-3 Fatty Acids for Indicated Prevention of Psychotic Disorders: A Randomized, Placebo-Controlled Trial. Arch Gen Psychiatry. 2010 Feb;67(2):146-54

  • Berger GE, Wood SJ, Wellard RM, Proffitt TM, McConchie M, Amminger GP, Jackson GD, Velakoulis D, Pantelis C, McGorry PD. Ethyl-eicosapentaenoic acid in first-episode psychosis. A 1H-MRS study. Neuropsychopharmacology. 2008 Sep;33(10):2467-73. Epub 2008 Jan 16. Erratum in: Neuropsychopharmacology. 2009 Jan;34(2):535.

  • du Bois TM, Deng C, Huang XF. Membrane phospholipid composition, alterations in neurotransmitter systems and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jul;29(6):878-88. Review.

  • Dyall SC, Michael GJ, Whelpton R, Scott AG, Michael-Titus AT. Dietary enrichment with omega-3 polyunsaturated fatty acids reverses age-related decreases in the GluR2 and NR2B glutamate receptor subunits in rat forebrain. Neurobiol Aging. 2007 Mar;28(3):424-39. Epub 2006 Feb 28.

  • Hibbeln JR, Makino KK, Martin CE, Dickerson F, Boronow J, Fenton WS. Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition among patients with schizophrenia or schizoaffective disorder. Biol Psychiatry 2003; 53(5):431-441.

  • Hibbeln JR, Umhau JC, Linnoila M, George DT, Ragan PW, Shoaf SE et al. A replication study of violent and nonviolent subjects: cerebrospinal fluid metabolites of serotonin and dopamine are predicted by plasma essential fatty acids. Biol Psychiatry 1998; 44(4):243-249.

  • Hibbeln JR. Seafood consumption and homicide mortality: A cross-national ecological analysis. 4th Congress of the International Society for the Study of Fatty Acids and

  • Joy CB, Mumby-Croft R, Joy LA. Polyunsaturated fatty acid supplementation for schizophrenia. Cochrane Database Syst Rev. 2006 Jul 19;3:CD001257. Review.

  • Khan MM, Evans DR, Gunna V, et al. Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with antipsychotics. Schizophr Res 2002;58(1):1-10.

  • Lipids (ISSFAL 2000). World Rev Nutr Diet 2001; 88:41-46.

  • Mahadik SP, Mukherjee S, Correnti EE, et al. Plasma membrane phospholipid and cholesterol distribution of skin fibroblasts from drug-naive patients at the onset of psychosis. Schizophr Res 1994;13(3):239-47.

  • Ohara K. The n-3 polyunsaturated fatty acid/dopamine hypothesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):469-74. Epub 2006 Dec 20. Review.

  • Peet M, Laugharne JD, Mellor J, Ramchand CN. Essential fatty acid deficiency in erythrocyte membranes from chronic schizophrenic patients, and the clinical effects of dietary supplementation. Prostaglandins Leukot Essent Fatty Acids. 1996 Aug;55(1-2):71-5. Review.

  • Schachter HM et al. Effects of Omega-3 Fatty Acids on Mental Health: Evidence Report/Technology Assessment Number 116. Prepared for the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services, July 2005. Accessed at http://www.ahrq.gov/clinic/tp/o3menttp.htm
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