Randomized, placebo-controlled trial of flax oil in pediatric bipolar disorder.
OBJECTIVE
This clinical trial evaluated whether supplementation with flax oil, containing the omega-3 fatty acid alpha-linolenic acid (alpha-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 alpha-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: %alpha-LNA (r = -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 alpha-LNA was 11.8 weeks versus 8 weeks for placebo; however, the longer treatment duration for alpha-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 alpha-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.
Gracious
Barbara L
BL
Department of Psychiatry, University of Rochester Medical Center/Strong Memorial Hospital, Laboratory for Mood Disorders in Children and Adolescents, Rochester, NY 14642, USA. barbara_gracious@urmc.rochester.edu
Chirieac
Madalina C
MC
Costescu
Stefan
S
Finucane
Teresa L
TL
Youngstrom
Eric A
EA
Hibbeln
Joseph R
JR
D000293:Adolescent; D016718:Arachidonic Acid / Q000097:blood; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D002648:Child; D003863:Depression / Q000188:drug therapy; D015118:Eicosapentaenoic Acid / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000097:blood; D005231:Fatty Acids, Unsaturated / Q000097:blood; D005260:Female; D006801:Humans; D008043:Linseed Oil / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D008297:Male; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D017962:alpha-Linolenic Acid / Q000009:adverse effects / Q000627:therapeutic use*
D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D017962:alpha-Linolenic Acid; D016718:Arachidonic Acid; D008043:Linseed Oil; D015118:Eicosapentaenoic Acid; C026219:docosapentaenoic acid
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