Omega-3 and Therapy Study for Childhood Bipolar Disorder- Not Otherwise Specified
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Study type: Interventional
Phase: Phase 1

Summary: 
      Childhood bipolar disorder- not otherwise specified (BP-NOS) was originally considered to be
      a milder version of bipolar disorder (BD). Research now indicates that BP-NOS is a highly
      impairing condition. No pharmacologic treatment guidelines exist for BP-NOS. Available
      evidence-based pharmacotherapy guidelines are for BP1; efficacious medications are,
      unfortunately, associated with significant risk for adverse events (Kowatch et al, 2005;
      2009). Previous research on diet and nutrition suggests that omega-3 (Ω3) fatty acids have a
      beneficial effect on mood, which might provide either a primary or adjunctive treatment with
      a more favorable risk:benefit ratio for children suffering from BP-NOS than currently
      available pharmacologic interventions. Psychoeducational psychotherapy (PEP) also has shown
      promise in treating bipolar spectrum disorders in children aged 8-12 (Fristad, 2006; Fristad,
      Verducci, Walters, & Young, 2009); its efficacy in treating BP-NOS specifically has not been
      determined.

      The current study compares Ω3, PEP, and their combination to a placebo supplement and active
      monitoring (AM) in a 12-week trial of 60 children with BP-NOS (15 each with Ω3, Ω3 plus PEP,
      PEP, and placebo, all with active monitoring). Primary goals are to determine: 1) feasibility
      of a) recruiting 60 participants in 2 years; b) participant retention over a 12-week trial;
      and 2) placebo-controlled effect sizes for Ω3, PEP, and combination treatment on manic and
      depressive symptoms. Secondary goals are to explore response curves over time, mediators and
      moderators, treatment response across a broad array of outcome variables, adherence to
      treatment, impact on physiologic parameters often worsened by mood stabilizing medications,
      and experience of side-effects in participants receiving Ω3 and/or PEP. Comparisons of
      results to a parallel study of children with depression with identical design will maximize
      knowledge gained. This pilot study of Ω3, PEP, and combined treatment will provide evidence
      about whether a larger trial is feasible and justified.
    

Detailed description: 
      Research indicates BP-NOS is a highly impairing condition comparable to the other bipolar
      spectrum disorders. Considerable gains have been made recently in understanding BP-NOS, in
      large part by research utilizing clear operational definitions for BP-NOS. However, clinical
      trials have focused on youth with Bipolar Disorder- Type I (BP1). No clinical guidelines
      exist for the treatment of BP-NOS.

      No pharmacologic treatment guidelines exist for BP-NOS. Available evidence-based
      pharmacotherapy guidelines are for BP1 and are associated with significant risk for adverse
      events. Additionally, while anti-manic agents have been identified, no study has demonstrated
      an effective anti-depressant agent for youth with bipolar depression. A review of weight gain
      and metabolic side effects of mood stabilizers and antipsychotic medications in 19 studies of
      pediatric bipolar patients found significant and clinically relevant weight increases in 18
      trials. Clinical trials of depression and bipolar disorders in children and adolescents show
      approximately 20%-25% of participants dropped out of short-term psychotropic medication
      treatment trials. Additionally, a recent study of an anticonvulsant mood stabilizer in
      children failed to show any superiority to placebo.

      Previous research on diet and nutrition suggests that omega-3 (Ω3) fatty acids have a
      beneficial effect on mood with little evidence of negative side-effects or deleterious drug
      interactions, suggesting Ω3 might function as either a primary or adjunctive treatment with a
      more favorable risk-benefit ratio for children suffering from BP than currently available
      pharmacologic interventions.Psychoeducational psychotherapy (PEP) also has shown promise in
      treating bipolar spectrum disorders in children aged 8-12 its efficacy in treating BP-NOS
      specifically has not been determined.

      The current study compares Ω3, PEP, and their combination to a placebo supplement, all with
      active monitoring (AM) in a 12-week trial of 60 children with BP-NOS (15 each with Ω3, Ω3
      plus PEP, PEP, and placebo. Primary goals are to determine: 1) feasibility of a) recruiting
      60 participants in 2 years; b) participant retention over a 12-week trial; and 2)
      placebo-controlled effect sizes for Ω3, PEP, and combination treatment on manic and
      depressive symptoms. Secondary goals are to explore response curves over time, mediators and
      moderators, treatment response across a broad array of outcome variables, adherence to
      treatment, impact on physiologic parameters often worsened by mood stabilizing medications,
      and experience of side-effects in participants receiving Ω3 and/or PEP. Comparisons of
      results to a parallel study of children with depression with identical design will maximize
      knowledge gained. This pilot study of Ω3, PEP, and combined treatment will provide evidence
      about whether a larger trial is feasible and justified.
    

Intervention name(s): Omega-3 Supplementation; Psychoeducational Psychotherapy (PEP); Placebo
Intervention type(s): Drug; Behavioral; Other
Intervention description(s): The Ω3 group will receive 1000 mg Ω3 (two 500 mg capsules, each containing 350 mg EPA: 50 mg DHA; 100 other Ω3) two times daily for a total daily dose of 2000 mg Ω3 (1400 mg EPA: 200 mg DHA; 400 other Ω3). The placebo group will receive two capsules two times daily matched for odor and appearance with the active intervention.; Therapy sessions occur twice a week for up to 24 sessions of manualized treatment. The importance of separating symptoms from the individual is emphasized. The family is offered support, validation, and recognition for their own difficult experiences in living with the child's mood disorder. Family members are taught that patients are particularly vulnerable to stress and tension; thus, therapists work with families to reduce the level of stress and tension in their homes. Improvement of communication, problem solving and coping strategies can lead to restoration of hope for recovery and decrease family dysfunction. Goals include strengthening the parent-child bond and helping children and parents feel competent to manage depression now and in future recurrences.; The placebo group will receive active monitoring (no IF-PEP) and two capsules two times daily matched for odor and appearance with the active intervention.
Other intervention name(s): Omega Brite; IF-PEP; Pbo
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: childhood bipolar disorder