OMEGA-3 FATTY ACIDS FOR INFLAMED DEPRESSION – A MATCH/MISMATCH STUDY

Abstract Background Despite decades of research on the pathophysiology of depression, the development of new therapeutic interventions has been slow, and no biomarkers of treatment response have been clinically implemented. Several lines of evidence suggets that the clinical and biological heterogeneity among patients with major depressive disorder (MDD) has hampered progress in this field. MDD with low-grade inflammation - "inflamed depression" - is a subtype of depression that may be associated with the superior antidepressant treatment response to anti-inflammatory compounds. Omega-3 fatty acoid eicosapentaenoic acid (EPA) has anti-inflammatory properties, and preliminary data suggest that it may be particulary efficacious in inflamed depression. Aims And Objectives In this study we tested the hypothesis that add-on EPA has greater antidepressant efficacy in MDD patients with high baseline high-sensititivity C-reactive protein (hs-CRP) compared to MDD patients with low hs-CRP. Method All subjects recevied 2.2 g EPA/day for 8 weeks, added to stable ongoing antidepressant treatment. The primary outcome was change in the 17-item Hamilton Depression Rating Scale (HAM-17). Patients and raters were blind to baseline hs-CRP status. Results In an intention-to-treat analysis including all subjects with at least one post baseline visit (n=101), a hs- CRP cut-off of >=1 mg/L, bot not >=3 mg/L, was associated with a greater improvement in HAMD-17 total score. In addition to a general antidepressant effect among patients with hs-CRP >= 1 mg/L, adjuvant EPA treatment improved symptoms putatively related to inflamed depression such as fatigue and sleep difficulties. Discussion And Conclusion The results suggests that EPA supplementation has a greater antidepressant effect in patients with mildy-moderately elevated hs-CRP compared to patients with lower hs-CRP. These findings add to the mounting evidence that stratificaton of MDD-subgroups based on inflammatory markers may be relevant to predict response to anti-inflammator interventions. Altough more studies are needed to confirm the most optimal cut-off to define these subgroups, this and other similar studies have the potential to facilitate the developement of targeted interventions and thereby break ground for precision medicine in psychiatry.