A Double-Blind Placebo-Controlled Trial of Omega-3 Fatty Acids As a Monotherapy for Adolescent Depression

Overview

Journal J Clin Psychiatry

Specialty Psychiatry

Date 2018 Jul 10

PMID 29985566

Citations 25

Authors

Vilma Gabbay

Rachel D Freed

Carmen M Alonso

Stefanie Senger

Jill Stadterman

Beth A Davison

Rachel G Klein

Affiliations

Soon will be listed here.

Abstract

Objective: Reports are mixed on the efficacy of omega-3 fatty acids (O3FA) for the treatment of major depressive disorder (MDD), with only limited data in adolescents. The present trial aimed to investigate systematically the efficacy of O3FA as a monotherapy, compared to a placebo, in adolescents with MDD. Secondarily, we explored O3FA effects on anhedonia, irritability, and suicidality-all key features of adolescent MDD.

Methods: Fifty-one psychotropic medication-free adolescents with DSM-IV-TR diagnoses of MDD (aged 12-19 years; 57% female) were randomized to receive O3FA or a placebo for 10 weeks. Data were collected between January 2006 and June 2013. O3FA and a placebo were administered on a fixed-flexible dose titration schedule based on clinical response and side effects. The initial dose of 1.2 g/d was increased 0.6 g/d every 2 weeks, up to a maximum of 3.6 g/d. Clinician-rated and self-rated depression severity, along with treatment response, served as primary outcome measures. Additionally, we examined O3FA effects on depression-related symptoms, including anhedonia, irritability, and suicidality. Treatment differences were analyzed via intent-to-treat analyses.

Results: O3FA were not superior to a placebo on any clinical feature, including depression severity and levels of anhedonia, irritability, or suicidality. Additionally, response rates were comparable between treatment groups. Within-treatment analyses indicated that both treatments were associated with significant improvement in depression severity on self- (O3FA: t = -4.38, P < .001; placebo: t = -3.52, P = .002) and clinician (O3FA: t = -6.47, P < .001; placebo: t = -8.10, P < .001) ratings.

Conclusions: In adolescents with MDD, O3FA do not appear to be superior to placebo.

Trial Registration: ClinicalTrials.gov identifier: NCT00962598.

Citing Articles

Omega-3 fatty acid supplementation for depression in children and adolescents.

Campisi S, Zasowski C, Bradley-Ridout G, Schumacher A, Szatmari P, Korczak D Cochrane Database Syst Rev. 2024; 11:CD014803.

PMID: 39564892 PMC: 11577543. DOI: 10.1002/14651858.CD014803.pub2.

The Efficacy of Omega-3 Fatty Acids as the Monotherapy for Depression: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

Wu S, Yang K, Liu W, Malau I, Zailani H, Chang C Nutrients. 2024; 16(21).

PMID: 39519521 PMC: 11547719. DOI: 10.3390/nu16213688.

Targeting Divergent Pathways in the Nutritional Management of Depression.

Tobin D, Vuckovic A, Sarris J Nutrients. 2024; 16(16).

PMID: 39203943 PMC: 11357244. DOI: 10.3390/nu16162806.

Omega-3 Polyunsaturated Fatty Acids in Depression.

Serefko A, Jach M, Pietraszuk M, Swiader M, Swiader K, Szopa A Int J Mol Sci. 2024; 25(16).

PMID: 39201362 PMC: 11354246. DOI: 10.3390/ijms25168675.

Nutraceuticals in Psychiatric Disorders: A Systematic Review.

Bozzatello P, Novelli R, Montemagni C, Rocca P, Bellino S Int J Mol Sci. 2024; 25(9).

PMID: 38732043 PMC: 11084672. DOI: 10.3390/ijms25094824.

References

Mozurkewich E, Clinton C, Chilimigras J, Hamilton S, Allbaugh L, Berman D . The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial. Am J Obstet Gynecol. 2013; 208(4):313.e1-9. PMC: 4010222. DOI: 10.1016/j.ajog.2013.01.038. View

Amminger G, Schafer M, Papageorgiou K, Klier C, Cotton S, Harrigan S . Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010; 67(2):146-54. DOI: 10.1001/archgenpsychiatry.2009.192. View

Libby A, Brent D, Morrato E, Orton H, Allen R, Valuck R . Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with SSRIs. Am J Psychiatry. 2007; 164(6):884-91. DOI: 10.1176/ajp.2007.164.6.884. View

Grosso G, Pajak A, Marventano S, Castellano S, Galvano F, Bucolo C . Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS One. 2014; 9(5):e96905. PMC: 4013121. DOI: 10.1371/journal.pone.0096905. View

Gabbay V, Liebes L, Katz Y, Liu S, Mendoza S, Babb J . The kynurenine pathway in adolescent depression: preliminary findings from a proton MR spectroscopy study. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 34(1):37-44. PMC: 2815014. DOI: 10.1016/j.pnpbp.2009.09.015. View

Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P . Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997; 36(7):980-8. DOI: 10.1097/00004583-199707000-00021. View

Marangell L, Martinez J, Zboyan H, Kertz B, Kim H, Puryear L . A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Am J Psychiatry. 2003; 160(5):996-8. DOI: 10.1176/appi.ajp.160.5.996. View

Gabbay V, Mao X, Klein R, Ely B, Babb J, Panzer A . Anterior cingulate cortex γ-aminobutyric acid in depressed adolescents: relationship to anhedonia. Arch Gen Psychiatry. 2011; 69(2):139-49. PMC: 3711232. DOI: 10.1001/archgenpsychiatry.2011.131. View

Gabbay V, Klein R, Guttman L, Babb J, Alonso C, Nishawala M . A preliminary study of cytokines in suicidal and nonsuicidal adolescents with major depression. J Child Adolesc Psychopharmacol. 2009; 19(4):423-30. PMC: 2778037. DOI: 10.1089/cap.2008.0140. View

10.

Mocking R, Harmsen I, Assies J, Koeter M, Ruhe H, Schene A . Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder. Transl Psychiatry. 2016; 6:e756. PMC: 4872453. DOI: 10.1038/tp.2016.29. View

11.

Gabbay V, Klein R, Alonso C, Babb J, Nishawala M, De Jesus G . Immune system dysregulation in adolescent major depressive disorder. J Affect Disord. 2008; 115(1-2):177-82. PMC: 2770721. DOI: 10.1016/j.jad.2008.07.022. View

12.

Li H, Liu D, Zhang E . [Effect of fish oil supplementation on fatty acid composition and neurotransmitters of growing rats]. Wei Sheng Yan Jiu. 2003; 29(1):47-9. View

13.

Bloch M, Qawasmi A . Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry. 2011; 50(10):991-1000. PMC: 3625948. DOI: 10.1016/j.jaac.2011.06.008. View

14.

Amminger G, Chanen A, Ohmann S, Klier C, Mossaheb N, Bechdolf A . Omega-3 fatty acid supplementation in adolescents with borderline personality disorder and ultra-high risk criteria for psychosis: a post hoc subgroup analysis of a double-blind, randomized controlled trial. Can J Psychiatry. 2013; 58(7):402-8. DOI: 10.1177/070674371305800705. View

15.

Adams P, Lawson S, Sanigorski A, Sinclair A . Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids. 1996; 31 Suppl:S157-61. DOI: 10.1007/BF02637069. View

16.

Appleton K, Sallis H, Perry R, Ness A, Churchill R . ω-3 Fatty acids for major depressive disorder in adults: an abridged Cochrane review. BMJ Open. 2016; 6(3):e010172. PMC: 4785331. DOI: 10.1136/bmjopen-2015-010172. View

17.

Raine A, Portnoy J, Liu J, Mahoomed T, Hibbeln J . Reduction in behavior problems with omega-3 supplementation in children aged 8-16 years: a randomized, double-blind, placebo-controlled, stratified, parallel-group trial. J Child Psychol Psychiatry. 2014; 56(5):509-20. PMC: 4336833. DOI: 10.1111/jcpp.12314. View

18.

Lucas M, Asselin G, Merette C, Poulin M, Dodin S . Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Am J Clin Nutr. 2009; 89(2):641-51. DOI: 10.3945/ajcn.2008.26749. View

19.

Sinn N, Milte C, Howe P . Oiling the brain: a review of randomized controlled trials of omega-3 fatty acids in psychopathology across the lifespan. Nutrients. 2012; 2(2):128-70. PMC: 3257637. DOI: 10.3390/nu2020128. View

20.

Silvers K, Woolley C, Hamilton F, Watts P, Watson R . Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression. Prostaglandins Leukot Essent Fatty Acids. 2005; 72(3):211-8. DOI: 10.1016/j.plefa.2004.11.004. View