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Effects of EPA on Major Depression Disorder (MDD) in People with High Body Mass Index (BMI)

major depressive disorder (MDD)

“We need a precision medicine approach” (Quoted from Dr. Maurizio Fava)

The health benefits of omega-3 fatty acids, specifically EPA and DHA, have been extensively studied.  While it has long been suspected that EPA and DHA may be beneficial in treatment of depression, optimal dosages for treatment have yet to be determined.  In a recent study published in the Journal of Clinical Psychiatry1 found that 4 g/day of EPA may help to alleviate major depressive disorder (MDD) in overweight individuals with elevated inflammatory response markers.  This study, which was completed in 2019, evaluated the effects of different doses of EPA in 45 people diagnosed with MDD who also had a body mass index (BMI) > 25 kg/m2, and plasma high-sensitivity C-reactive protein (hs-CRP) levels ≥ 3.0 mg/L.  Participants were divided into groups and received daily dosages of 1 g/day, 2 g/day or 4 g/day of EPA, or placebo for 12 weeks.  The authors found that a dose of 4 g/day of EPA resulted in sustained improvements in MDD and decreases in hs-CRP levels.  

The results of this study suggest that doses of EPA higher than the typical 1-2 g/day used in psychiatry may be more effective for depression in some patients with chronic inflammation. The results of this recent study1 are consistent with a previous study2 performed by the same research group which found that chronic inflammation and elevated C-reactive protein can be positively affected by EPA.

Dr. Maurizio Fava, Psychiatrist in Chief at Massachusetts General Hospital and one of the authors of the study, spoke with KD Pharma about the importance of this research. According to Dr. Fava, major depressive disorder is a highly prevalent condition that effects 1/5 people in their lifetime. “During the pandemic we’ve seen a tripling of anxiety and depression in the younger population, 18-24. We’ve never seen anything like this. It’s a highly prevalent condition that has become even more prevalent with the pandemic.” More than 40,000 people in the US die by suicide each year and MDD is a strong risk factor.  When asked about the importance of this research, Dr. Fava responded that “We need new tools and we need a precision medicine approach. The science, in some ways, has to focus on how to identify the best treatment for a given patient.” 
Previous research2 has indicated that a significant portion of patients with MDD have elevated levels of proinflammatory cytokines, including CRP, and those with the highest levels of these inflammatory markers showed the most robust response to omega-3 fatty acids. In the current study1, patients with MDD, elevated CRP and obesity, which is another contributing factor to chronic inflammation. This study was the first dose-finding study for omega-3 fatty acids and depression.  “We found that 4 g was the one that had the most robust effect on depression, even though in clinical practice most people have, for years, been using 1 g of omega-3.” Doses of EPA higher than those that are usually recommended may be more effective for depression in patients with obesity and chronic inflammation.  “The study needs to be replicated in a larger sample, but it seems very promising that two studies now from our group have consistently showed that in patients with chronic inflammation and elevated CRP that omega-3 EPA may be an effective treatment.”  

1.    Mischoulon D, Dunlop BW, Kinkead B, Schettler PJ, Lamon-Fava S, Rakosfsky JJ, Nirenberg AA, Clain AJ, Crowe TM, Wong A, Felger JC, Sangermano L, Fava M, Rapaport MH (2022) Omega-3 Fatty Acids for Major Depressive Disorder with High Inflammation: A Randomized Dose-Finding Clinical Trial.  Journal of Clinical Psychiatry, 83(5):21m14074.
2.    Rapaport MH, Nierenberg AA, Schettler PJ, Kinkead B, Cardoos A, Walker R, Mischoulon D (2016) Inflammation as a Predictive Biomarker for Response to Omega-3 Fatty Acids in Major Depressive Disorder: A Proof of Concept Study. Molecular Psychiatry, 21(1):71-79.