title: Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials.
abstract: BACKGROUND
  Despite omega-3 polyunsaturated fatty acids (PUFA) supplementation in depressed patients have been suggested to improve depressive symptomatology, previous findings are not univocal.
  
  
  OBJECTIVE
  To conduct an updated meta-analysis of randomized controlled trials (RCTs) of omega-3 PUFA treatment of depressive disorders, taking into account the clinical differences among patients included in the studies.
  
  
  METHODS
  A search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of RCTs using omega-3 PUFA on patients with depressive symptoms published up to August 2013 was performed. Standardized mean difference in clinical measure of depression severity was primary outcome. Type of omega-3 used (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and omega-3 as mono- or adjuvant therapy was also examined. Meta-regression analyses assessed the effects of study size, baseline depression severity, trial duration, dose of omega-3, and age of patients.
  
  
  RESULTS
  Meta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized difference in random-effects model 0.56 SD [95% CI: 0.20, 0.92] and 0.22 SD [95% CI: 0.01, 0.43], respectively; pooled analysis was 0.38 SD [95% CI: 0.18, 0.59]). Use of mainly EPA within the preparation, rather than DHA, influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations, perinatal depression, primary disease other than depression and healthy subjects.
  
  
  CONCLUSIONS
  The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD.
authors.affiliation: Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grosso
authors.affiliation: Department of Epidemiology and Population Studies, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pajak
authors.affiliation: Department "G.F. Ingrassia", Section of Hygiene and Public Health, University of Catania, Catania, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Marventano
authors.affiliation: Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Castellano
authors.affiliation: Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Galvano
authors.affiliation: Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bucolo
authors.affiliation: Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.affiliation: Department of Educational Sciences, University of Catania, Catania, Italy; IRCCS Associazione Oasi Maria S.S. - Institute for Research on Mental Retardation and Brain Aging, Troina, Enna, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Caraci
mesh_terms: D003866:Depressive Disorder / Q000178:diet therapy* / Q000378:metabolism* / Q000473:pathology; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000627:therapeutic use; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016239:MEDLINE; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic
chemical_list: D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid