Omega-3 Fatty Acids & Psychoeducational Psychotherapy for Child Bipolar NOS

描述（由申请人提供）：最初被认为是双相情感障碍（BD）的轻度版本，现在研究表明双相情感障碍-未另行指定（BP-NOS）是一种高度损害的疾病。最近在了解BP-NOS方面取得了相当大的进展，这在很大程度上是通过对BP-NOS进行明确的操作定义的研究（参见nimh资助的双相青年的过程和结果[COBY]和躁狂症状的纵向评估[LAMS]研究）。然而，临床试验主要集中在青少年双相情感障碍- I型（BP1）。BP-NOS的治疗尚无临床指南。BP-NOS在高峰症状严重程度、自杀意念和合并症数量方面与BP1和BP2相似；在功能损伤方面，它与BP2相似（Axelson et al, 2006）。然而，BP-NOS患者的恢复速度比BP1或BP2患者慢三倍，并且经历更多的情绪不稳定（Birmaher et al, 2006）。与被诊断为BP1和BP2的青少年相比，他们也更有可能保持亚综合征状态，而不是变得无症状（Birmaher等人，2006）。现有的循证药物治疗指南适用于BP1；不幸的是，有效的药物与不良事件的重大风险相关（Kowatch, Fristad, Findling & Post, 2009）。因此，与我们有临床试验数据的诊断为BP1的青少年相比，用精神药物治疗这些青少年的风险：收益比存在更大的不平衡。先前关于饮食和营养的研究表明，omega-3 (？3)脂肪酸对情绪有有益的影响，与目前可用的药物干预相比，脂肪酸可作为BP-NOS患儿的主要或辅助治疗，其风险效益比更有利。心理教育心理治疗（PEP）在治疗8-12岁儿童双相情感障碍方面也显示出希望（Fristad, 2006; Fristad, Verducci, Walters, & Young, 2009）；其治疗BP-NOS的疗效尚未确定。目前的研究比较了？在一项为期12周的试验中，60名BP-NOS儿童（每个15名）接受了安慰剂补充和主动监测（AM）。3、?3加PEP， PEP和安慰剂，均有主动监测)。主要目标是确定：1)可行性a)在2年内招募60名参与者；B)参与者在12周试验期间的保留率；2)安慰剂控制的效应值为？3、PEP，以及对躁狂抑郁症状的联合治疗。次要目标是探索随时间变化的反应曲线、调节因子和调节因子、一系列结果变量的治疗反应、对治疗的依从性、对生理参数的影响（通常因情绪稳定药物而恶化），以及接受？3和/或PEP将结果与具有相同设计的抑郁症儿童的平行研究进行比较将最大限度地获得知识。这个试点研究？3、PEP和

DESCRIPTION (provided by applicant): Originally considered to be a milder version of bipolar disorder (BD), research now indicates bipolar disorder- not otherwise specified (BP-NOS) is a highly impairing condition. Considerable gains have been made recently in understanding BP-NOS, in large part by research utilizing clear operational definitions for BP-NOS (cf. the NIMH-funded Course and Outcome of Bipolar Youth [COBY] and Longitudinal Assessment of Manic Symptoms [LAMS] studies). However, clinical trials have focused on youth with Bipolar Disorder- Type I (BP1). No clinical guidelines exist for the treatment of BP-NOS. BP-NOS is similar to BP1 and BP2 in terms of peak symptom severity, suicidal ideation, and number of comorbidities; it is similar to BP2 in terms of functional impairment (Axelson et al, 2006). However, youth with BP-NOS are three times slower to recover and experience more mood lability than youth with BP1 or BP2 (Birmaher et al, 2006). They are also more likely to remain sub- syndromal rather than becoming asymptomatic compared to youth diagnosed with BP1 and BP2 (Birmaher et al, 2006). Available evidence-based pharmacotherapy guidelines are for BP1; efficacious medications are, unfortunately, associated with significant risk for adverse events (Kowatch, Fristad, Findling & Post, 2009). Thus, there is a greater imbalance in the risk:benefit ratio of treating these youth with psychotropics compared to the risk:benefit ratio of treating youth diagnosed with BP1, for whom we have clinical trial data. Previous research on diet and nutrition suggests that omega-3 (?3) 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 ?3, 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 ?3, ?3 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 ?3, 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 ?3 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 ?3, PEP, and combined treatment will provide evidence about whether a larger trial is feasible and justified. PUBLIC HEALTH RELEVANCE: Childhood onset bipolar disorder-not otherwise specified (BP-NOS) is highly impairing. However, no treatment guidelines are designed specifically for it; current clinical practice is guided by treatments for BP1. Limitations of currently available treatments have led researchers to explore alternatives for more effective and/or safer treatment options; long-chain omega-3 fatty acids and family-based psychoeducational psychotherapy (PEP) have promising but non-decisive preliminary results. This small randomized, controlled study will examine feasibility of studying the effects of ?3 dietary supplementation, PEP, and combined treatment on reducing symptoms of depression and mania in children diagnosed with BP-NOS. Knowledge will be maximized by comparing results to those from a parallel study for children with depression.