The following is the summary of “Efficacy of eicosapentaenoic acid in inflammatory depression: study protocol for a match-mismatch trial” published in the December 2022 issue of Psychiatry by Suneson, et al.

Studies of antidepressant efficacy have often included only those who meet the DSM-IV criteria for Major Depressive Disorder (MDD). Due to the multifactorial nature of MDD, this method may have masked important distinctions between patients and delayed the creation of more effective, individualized therapies. Biomarkers can be used to identify specific forms of depression or endophenotypes, and then focused interventions can be tested to determine their effectiveness. There is mounting evidence that the subtype of depression known as “inflammatory depression” has important therapeutic implications. This study intends to investigate the idea that omega-3 fatty acids, due to their anti-inflammatory and neuroprotective effects, are effective in this subtype of depression.

To determine whether supplementation with eicosapentaenoic acid (EPA), an omega-3 fatty acid, alleviates depressive symptoms in patients with major depressive disorder (MDD) and low-grade systemic inflammation, researchers undertake a match-mismatch experiment. Patients with MDD who are responding well to antidepressant treatment are divided into high-inflammation (hs-CRP  ≥3 mg/L) and low-inflammation (hs-CRP  ≥3  mg/L) groups at the outset, based on their baseline levels of this marker. Supplemental EPA (2 g/day) is given to both groups for a total of 8 weeks, and there are 3 visits throughout the trial where blood is drawn. Inflammation status is not revealed to patients or raters. Change from baseline to week 8 on the Hamilton Depression Rating Scale is the primary outcome measure. To that end, researchers postulate that EPA will have a more profound antidepressant effect in the inflammation group than in the non-inflammation group. 

Quality of life, anxiety, anhedonia, sleep difficulties, fatigue, cognitive function, and changes in biomarkers related to inflammation, oxidative stress, metabolomics, and cellular aging are all secondary outcomes. For the first time, researchers will use a match-mismatch trial design to see if omega-3 is an effective treatment for inflammatory depression in this investigation. If the results of their research pan out, it will be a step forward for precision psychiatry.

Source: bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-022-04430-z