Low omega‐3 polyunsaturated fatty acids predict reduced response to standard antidepressants in patients with major depressive disorder

• Published in: Depression and anxiety Vol. 39; no. 5; pp. 407 - 418
• Main Authors: Cussotto, Sofia, Delgado, Inês, Oriolo, Giovanni, Kemper, Jonas, Begarie, Diane, Dexpert, Sandra, Sauvant, Julie, Leboyer, Marion, Aouizerate, Bruno, Martin‐Santos, Rocío, Schaefer, Martin, Capuron, Lucile
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.05.2022; Wiley
• Subjects: Antidepressants; Antidepressive Agents - therapeutic use; Citalopram; clinical response; Depressive Disorder, Major - drug therapy; DHA; Docosahexaenoic acid; Docosahexaenoic Acids - therapeutic use; Eicosapentaenoic acid; Eicosapentaenoic Acid - pharmacology; Eicosapentaenoic Acid - therapeutic use; Fatty acids; Fatty Acids, Omega-3 - therapeutic use; Fatty Acids, Unsaturated - therapeutic use; Fish oils; Humans; Life Sciences; MADRS; major depressive disorder; Mental depression; Neurons and Cognition; omega‐3 PUFAs; Patients; Phenotypes; Polyunsaturated fatty acids; Sertraline; Treatment resistance; Venlafaxine; clinical response; MADRS; antidepressants; major depressive disorder; DHA; omega-3 PUFAs
• ISSN: 1091-4269; 1520-6394; 1520-6394
• DOI: 10.1002/da.23257

Background Major depressive disorder (MDD) is characterized by a high rate of treatment resistance. Omega (ω)−3 polyunsaturated fatty acids (PUFAs) were shown to correlate with depressive phenotype both in rodents and in humans. However, few studies to date have investigated the role of PUFAs in antidepressant response. The primary aim of this study was to assess the link between baseline PUFA composition and changes in depressive symptoms as well as antidepressant response in a multicenter study of depressed patients. Methods Sixty depressed adults who met criteria for MDD according to DSM‐IV‐TR were recruited. Neuropsychiatric evaluations occurred at baseline and after 4 and 8 weeks of treatment with standard antidepressants, including escitalopram (N = 45), sertraline (N = 13) and venlafaxine (N = 2). At study endpoint, patients were stratified into responders (R) or non‐responders (NR) based on their MADRS (Montgomery‐Åsberg Depression Rating Scale) score. Baseline PUFA levels were assessed and their association with clinical response was determined. Results Lower ω−3 PUFA levels were associated to worse baseline symptomatology. Baseline levels of PUFAs were significantly different between R and NR, with R exhibiting lower docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and ω−3 index; and higher ω‐6/ω−3 ratio than NR before the start of antidepressant treatment. DHA levels as well as the ω−3 index and ω‐6/ω−3 ratio significantly predicted response to antidepressants at study endpoint. Conclusions These results show that baseline levels of PUFAs predict later response to standard antidepressants in depressed subjects. They suggest that PUFA intake and/or metabolism represent a novel modifiable tool for the management of unresponsive depressed patients.