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

描述(申请人提供)：最初被认为是双相情感障碍(BD)的较轻版本，现在的研究表明双相情感障碍-未另行规定(BP-NOS)是一种高度损害的情况。最近在理解BP-NOS方面取得了相当大的进展，这在很大程度上是通过研究利用BP-NOS的明确操作定义(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，临床试验的重点是患有I型双相情感障碍(BP1)的年轻人。目前尚无治疗BP-NOS的临床指南。BP-NOS在高峰症状严重性、自杀意念和合并症数量方面与BP1和BP2相似；在功能损害方面与BP2相似(Axelson等人，2006年)。然而，患有BP-NOS的年轻人恢复速度是患有BP1或BP2的年轻人的三倍，并且经历了更多的情绪不稳定(Birmaher等人，2006年)。与诊断为BP1和BP2的年轻人相比，他们也更有可能保持亚症状，而不是变得没有症状(Birmaher等人，2006年)。现有的循证药物治疗指南适用于BP1；不幸的是，有效的药物治疗与不良事件的重大风险相关(Koatch，Fristad，Findling&Post，2009)。因此，与我们有临床试验数据的治疗确诊为BP1的年轻人的风险：收益比相比，使用精神药物治疗这些青年的风险：收益比存在更大的不平衡。以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，这可能提供一种主要或辅助治疗，具有更有利的风险：与目前可用的药物干预措施相比，对患有BP-NOS的儿童的受益比率。心理教育心理疗法(PEP)在治疗8-12岁儿童的双相情感障碍方面也显示出了希望(Fristad，2006；Fristad，Verducci，Walters，&Young，2009)；其对BP-NOS的具体治疗效果尚未确定。本研究对60名BP-NOS儿童进行了为期12周的试验，将？3、PEP及其组合与安慰剂补充剂和主动监测(AM)进行了比较(15名儿童分别服用？3、？3加PEP、PEP和安慰剂，均有积极监测)。主要目标是确定：1)在两年内招募60名参与者的可行性；b)在12周的试验中保留参与者；以及2)安慰剂对照效应大小？3，PEP，以及对躁狂和抑郁症状的联合治疗。次要目标是探索随着时间的推移的反应曲线、调节因素和调节因素、对各种结果变量的治疗反应、对治疗的坚持、对经常因情绪稳定药物而恶化的生理参数的影响，以及接受？3和/或PEP的参与者的副作用体验。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，将使获得的知识最大化。这项关于？3、PEP和 联合治疗将为更大规模的试验是否可行和合理提供证据。 公共卫生相关性：儿童期起病双相情感障碍--未另行说明(BP-NOS)严重损害健康。然而，没有专门为它设计的治疗指南；目前的临床实践是由BP1的治疗指导的。目前可用治疗的局限性导致研究人员探索更有效和/或更安全的治疗方案的替代方案；长链omega-3脂肪酸和基于家庭的心理教育心理治疗(PEP)具有有希望但非决定性的初步结果。这项小型随机对照研究将考察膳食补充、PEP和联合治疗对诊断为BP-NOS的儿童抑郁和躁狂症状的缓解效果的可行性。通过将结果与一项针对抑郁症儿童的平行研究的结果进行比较，将使知识最大化。

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.