The majority of numerous studies associate low blood levels of omega-3s with greater risk of depression.
Depression is a risk factor for death or injury in people with CHD, so it makes sense to test the effects of anti-depressants in patients who are diagnosed with depression.
It also makes sense to test the effects of nutrients with antidepressant potential, such as omega-3s.
And judging by the headlines that raced around the world last week – like “Study fails to find omega 3 benefit for depression” – you’d think that a new study had found omega-3s ineffective for alleviating depression.
But most headlines misstated both the purpose and outcome of the clinical trial published this month in the Journal of the American Medical Association (JAMA).
Despite what the headlines implied, this trial only tested omega-3s as an adjunct to the FDA-approved antidepressant drug Zoloft® … not as a stand-alone treatment for depression.
In fact, the study only showed that omega-3s from fish oil did not add extra mood benefits to those conferred by an antidepressant drug.
Worse, virtually none of the many media reports mentioned that two prior clinical trials found that omega-3s from fish oil substantially increased the efficacy of various antidepressant drugs.
As the authors of a UK trial wrote seven years ago, “Treatment with [omega-3] EPA at a dosage of 1 gram per day was effective in treating depression in patients who remained depressed despite adequate standard therapy.” (Peet M, Horrobin DF 2002)
That same year, an Israeli team penned this encouraging conclusion to their clinical study: “Highly significant benefits of the addition of the omega-3 fatty acid compared with placebo were found by week 3 of treatment.” (Nemets B et al. 2002)
Media has short memory on omega-3s and depression
And with regard to the clinical record on omega-3s and depression, the memory spans of most reporters and editors seem laughably short.
From the headlines, you’d never know that the outcomes of a major clinical trial published just two months back suggest that omega-3s can approximate the effects of anti-depressant drugs for alleviating depression symptoms … excepting those who are also diagnosed with anxiety disorder (“Fish Oil Rivals Antidepressants in Clinical Trial”).
As that study’s lead author, Francois Lesperance, M.D., told Medscape Psychiatry, “... the level of improvement we saw in this subgroup [i.e., people diagnosed with depression but not anxiety] is on a par with what has typically been reported with pharmacologic [drug] treatments.” (Stein J 2009)
Importantly, there are plausible biological mechanisms by which omega-3s could affect mood … see “How omega-3s might help”, below.
New trial found no additional benefits from adding omega-3s to drug treatment
Researchers from the Washington University School of Medicine conducted a clinical trial – randomized, double-blind, and placebo-controlled – in 122 patients diagnosed with major depression and CHD (Carney RM et al. 2009).
All of the participants took the antidepressant drug sertraline (50 mg daily) – better known as Zoloft® or Lustral® – for 10 weeks.
Like Prozac®, sertraline belongs to the newer class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), which work (in part) by boosting brain levels of the mood-elevating neurotransmitter serotonin.
About half of the patients also took 2 grams of omega-3s per day (930mg of EPA and 750mg of DHA), while the others took inactive placebo capsules.
The Washington University team rated the participants’ levels of depression and anxiety using standard psychiatric tests.
The results showed no difference between the drug+placebo and drug+omega-3 groups in terms of the patients’ depression and anxiety test scores.
Likewise, there was no significant difference between the two groups in terms of their rates of remission or their overall responses to sertraline (Zoloft/Lustral).
Possible reasons for the lack of added benefit
Both of the positive trials published in 2002 involved otherwise healthy people who’d been diagnosed with major depression (Peet M, Horrobin DF 2002; Nemets B et al. 2002).
In contrast, the new JAMA trial involved people diagnosed with both major depression and coronary heart disease (CHD): a mutually reinforcing pair of conditions.
And the authors themselves recognized some limitations of their trial.
They noted that it may have been too short to reveal the full potential of adding omega-3s to sertraline, and that the amounts and relative proportions of omega-3 fats (EPA and DHA) in the fish oil used may not have been ideal.
As they wrote, “Whether higher doses of EPA, DHA, or sertraline, a longer duration of treatment, or the use of omega-3 as monotherapy (i.e., omega-3s taken alone, without any drugs) can improve depression in patients with stable heart disease remains to be determined.” (Carney RM et al. 2009)
How omega-3s might help
Omega-3s are essential to the proper function of brain-cell membranes, and studies led by NIH clinical researcher Joseph Hibbeln, M.D., suggest that dietary omega-3s raise serotonin levels (Hibbeln JR et al. 1998).
Dr. Hibbeln’s study found that low levels of omega-3s in cell membranes were associated with low levels of serotonin in people with aggression and impulse-control problems.
Among other effects, this could help explain the strong, well-documented associations between higher omega-3 intakes and reduced risk of depression.
In addition, omega-3s and SSRI drugs alike foster growth of cells in the brain’s hippocampus region, and connections between hippocampus brain cells … an effect associated with reduced depression risk and symptom severity.
In mouse studies, omega-3s and fluoxetine (Prozac) both restore brain cells’ ability to take on new roles and form new connections, which eases the symptoms of depression (Sahay A, Hen R 2008; Venna VR et al. 2009).
The media distorted the meaning of the new study published in JAMA … and sadly, we’re not surprised, since dramatic, negative headlines draw more attention than reasonable, nuanced news reports.
Sources
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Carney RM, Freedland KE, Rubin EH, Rich MW, Steinmeyer BC, Harris WS. Omega-3 augmentation of sertraline in treatment of depression in patients with coronary heart disease: a randomized controlled trial. JAMA. 2009 Oct 21;302(15):1651-7.
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Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, Keck PE Jr, Marangell LB, Richardson AJ, Lake J, Stoll AL. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry. 2006 Dec;67(12):1954-67. Review.
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Hibbeln JR, Linnoila M, Umhau JC, Rawlings R, George DT, Salem N Jr. Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics. Biol Psychiatry 1998; 44: 235-242.
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Hibbeln JR. Seafood consumption and homicide mortality. A cross-national ecological analysis. World Rev Nutr Diet. 2001;88:41-6.
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Nemets B, Stahl Z, Belmaker RH. Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Am J Psychiatry. 2002;159(3):477-479.
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Owen C, Rees AM, Parker G. The role of fatty acids in the development and treatment of mood disorders. Curr Opin Psychiatry. 2008 Jan;21(1):19-24.
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Peet M, Horrobin DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry. 2002;59(10):913-919.
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Sahay A, Hen R. Hippocampal neurogenesis and depression. Novartis Found Symp. 2008;289:152-60; discussion 160-4, 193-5.
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Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003 Aug 8;301(5634):805-9.
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Venna VR, Deplanque D, Allet C, Belarbi K, Hamdane M, Bordet R. PUFA induce antidepressant-like effects in parallel to structural and molecular changes in the hippocampus. Psychoneuroendocrinology. 2009 Feb;34(2):199-211. Epub 2008 Oct 10.
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