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Randomized, placebo-controlled trial of flax oil in pediatric bipolar disorder

Authors

  • Barbara L Gracious,

    1. Department of Psychiatry, University of Rochester Medical Center/Strong Memorial Hospital, Laboratory for Mood Disorders in Children and Adolescents, Rochester, NY
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  • Madalina C Chirieac,

    1. Department of Psychiatry, University of Rochester Medical Center/Strong Memorial Hospital, Laboratory for Mood Disorders in Children and Adolescents, Rochester, NY
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  • Stefan Costescu,

    1. Department of Psychiatry, University of Rochester Medical Center/Strong Memorial Hospital, Laboratory for Mood Disorders in Children and Adolescents, Rochester, NY
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  • Teresa L Finucane,

    1. Department of Psychiatry, University of Rochester Medical Center/Strong Memorial Hospital, Laboratory for Mood Disorders in Children and Adolescents, Rochester, NY
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  • Eric A Youngstrom,

    1. Department of Psychiatry and Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC
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  • Joseph R Hibbeln

    1. Section on Nutritional Neurochemistry, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
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  • These data were presented in part at the NIMH Pediatric Bipolar Conference, April 1, 2006, Chicago, IL, USA and at the American Academy of Child and Adolescent Psychiatry 54th Annual Meeting, Boston, MA, USA, October 23, 2007 poster session.

  • BLG has served as a consultant for Janssen/Johnson & Johnson. MCC, SC, TLF, EAY, and JRH have no conflicts of interest to report in relation to this manuscript.

Corresponding author:
Barbara L. Gracious, M.D.
Department of Psychiatry
University of Rochester Medical Center
300 Crittenden Boulevard
Rochester, NY 14642, USA
Fax: 585-276-2065
E-mail: barbara_gracious@urmc.rochester.edu

Abstract

Gracious BL, Chirieac MC, Costescu S, Finucane TL, Youngstrom EA, Hibbeln JR. Randomized, placebo-controlled trial of flax oil in pediatric bipolar disorder.
Bipolar Disord 2010: 12: 142–154. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  This clinical trial evaluated whether supplementation with flax oil, containing the omega-3 fatty acid α-linolenic acid (α-LNA), safely reduced symptom severity in youth with bipolar disorder.

Methods:  Children and adolescents aged 6–17 years with symptomatic bipolar I or bipolar II disorder (n = 51), manic, hypomanic, mixed, or depressed, were randomized to either flax oil capsules containing 550 mg α-LNA per 1 gram or an olive oil placebo adjunctively or as monotherapy. Doses were titrated to 12 capsules per day as tolerated over 16 weeks. Primary outcomes included changes in the Young Mania Rating Scale, Child Depression Rating Scale-Revised, and Clinical Global Impressions-Bipolar ratings using Kaplan-Meier survival analyses.

Results:  There were no significant differences in primary outcome measures when compared by treatment assignment. However, clinician-rated Global Symptom Severity was negatively correlated with final serum omega-3 fatty acid compositions: %α-LNA (= −0.45, p < 0.007), % eicosapentaenoic acid (EPA) (r = −0.47, p < 0.005); and positively correlated with final arachidonic acid (AA) (r = 0.36, p < 0.05) and docosapentaenoic acid (DPA) n-6 (r = 0.48, p < 0.004). The mean duration of treatment for α-LNA was 11.8 weeks versus 8 weeks for placebo; however, the longer treatment duration for α-LNA was not significant after controlling for baseline variables. Subjects discontinued the study for continued depressive symptoms.

Conclusions:  Studies of essential fatty acid supplementation are feasible and well tolerated in the pediatric population. Although flax oil may decrease severity of illness in children and adolescents with bipolar disorder who have meaningful increases in serum EPA percent levels and/or decreased AA and DPA n-6 levels, individual variations in conversion of α-LNA to EPA and docosahexaenoic acid as well as dosing burden favor the use of fish oil both for clinical trials and clinical practice. Additionally, future research should focus on adherence and analysis of outcome based on changes in essential fatty acid tissue compositions, as opposed to group randomization alone.

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