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。

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.