title: A randomized clinical trial of high eicosapentaenoic acid omega-3 fatty acids and inositol as monotherapy and in combination in the treatment of pediatric bipolar spectrum disorders: a pilot study.
abstract: OBJECTIVE
  We conducted a 12-week, randomized, double-blind, controlled clinical trial to evaluate the effectiveness and tolerability of high eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) omega-3 fatty acids and inositol as monotherapy and in combination in children with bipolar spectrum disorders.
  
  
  METHODS
  Participants were children 5-12 years of age meeting DSM-IV diagnostic criteria for bipolar spectrum disorders (bipolar I or II disorder or bipolar disorder not otherwise specified [NOS]) and displaying mixed, manic, or hypomanic symptoms. Subjects with severe illness were excluded. Subjects were randomized to 1 of 3 treatment arms: inositol plus placebo, omega-3 fatty acids plus placebo, and the combined active treatment of omega-3 fatty acids plus inositol. Data were collected from February 2012 to November 2013.
  
  
  RESULTS
  Twenty-four subjects were exposed to treatment (≥ 1 week of study completed) (inositol [n = 7], omega-3 fatty acids [n = 7], and omega-3 fatty acids plus inositol [n =10]). Fifty-four percent of the subjects completed the study. Subjects randomized to the omega-3 fatty acids plus inositol arm had the largest score decrease comparing improvement from baseline to end point with respect to the Young Mania Rating Scale (P < .05). Similar results were found for the Children's Depression Rating Scale (P < .05) and the Brief Psychiatric Rating Scale (P <.05).
  
  
  CONCLUSIONS
  Results of this pilot randomized, double-blind, controlled trial suggest that the combined treatment of omega-3 fatty acids plus inositol reduced symptoms of mania and depression in prepubertal children with mild to moderate bipolar spectrum disorders. Results should be interpreted in light of limitations, which include exclusion of severely ill subjects, 54% completion rate, and small sample size.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01396486.
authors.affiliation: Clinical and Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital, Boston.|Harvard Medical School, Boston, Massachusetts.
authors.forename: Janet
authors.initials: J
authors.lastname: Wozniak
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: James
authors.initials: J
authors.lastname: Chan
authors.forename: Laura
authors.initials: L
authors.lastname: Tarko
authors.forename: Mariely
authors.initials: M
authors.lastname: Hernandez
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Davis
authors.forename: K Yvonne
authors.initials: KY
authors.lastname: Woodworth
authors.forename: Joseph
authors.initials: J
authors.lastname: Biederman
mesh_terms: D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007294:Inositol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010865:Pilot Projects; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D004281:Docosahexaenoic Acids; D007294:Inositol; D015118:Eicosapentaenoic Acid