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

Sofia Cussotto, Inês Delgado, Giovanni Oriolo, Jonas Kemper, Diane Begarie, Sandra Dexpert, Julie Sauvant, Marion Leboyer, Bruno Aouizerate, Rocío Martin‐Santos, Martin Schaefer, Lucile Capuron
Depression and Anxiety. 2022-03-31; 39(5): 407-418
DOI: 10.1002/da.23257

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1. Depress Anxiety. 2022 May;39(5):407-418. doi: 10.1002/da.23257. Epub 2022 Mar
31.

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

Cussotto S(1), Delgado I(1), Oriolo G(2)(3), Kemper J(4), Begarie D(5), Dexpert
S(1), Sauvant J(1), Leboyer M(6)(7), Aouizerate B(1)(8), Martin-Santos R(2)(3),
Schaefer M(4)(9), Capuron L(1).

Author information:
(1)University of Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux,
France.
(2)Department of Psychiatry and Psychology, Hospital Clinic, IDIBAPS, CIBERSAM,
Barcelona, Spain.
(3)Department of Medicine, Institute of Neuroscience, University of Barcelona,
Barcelona, Spain.
(4)Department of Psychiatry, Psychotherapy, Psychosomatics, and Addiction
Medicine, Evang. Kliniken Essen-Mitte, Essen, Germany.
(5)Departement de Biologie, École Normale Supérieure de Lyon, Université Claude
Bernard Lyon I, Université de Lyon, Lyon, France.
(6)INSERM, U955, Translational Neuro-Psychiatry lab, Institut Mondor de
Recherche Biomédicale, Créteil, France.
(7)AP-HP, Département Universitaire d’Addictologie et Psychiatrie des Hôpitaux
Henri Mondor University Hospital, Université Paris Est Créteil, Créteil, France.
(8)CH Charles Perrens, Pôle de Psychiatrie Générale et Universitaire, Centre de
référence régional des pathologies anxieuses et dépressives, Bordeaux, France.
(9)Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin
Berlin, Berlin, Germany.

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.