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）的一种较温和的版本，现在研究表明双相情感障碍-未另行说明（BP-NOS）是一种高度损害性疾病。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利用BP-NOS的明确操作定义的研究（参见NIMH资助的双相青年[COBY]和躁狂症状纵向评估[LAMS]研究）。然而，临床试验主要集中在患有双相情感障碍-I型（BP 1）的青少年身上。目前尚无治疗BP-NOS的临床指南。BP-NOS在峰值症状严重程度、自杀意念和合并症数量方面与BP 1和BP 2相似;在功能损害方面与BP 2相似（Axelson et al，2006）。然而，患有BP-NOS的青少年比患有BP 1或BP 2的青少年恢复慢三倍，并且经历更多的情绪不稳定性（Birmaher等人，2006）。与诊断为BP 1和BP 2的青年相比，他们也更可能保持亚综合征而不是变得无症状（Birmaher et al，2006）。现有的循证药物治疗指南是针对BP 1的;不幸的是，有效的药物与不良事件的显著风险相关（Kowatch，弗里斯塔德，Findling & Post，2009）。因此，与治疗诊断为BP 1的青少年的风险：获益比相比，用精神药物治疗这些青少年的风险：获益比存在更大的不平衡，我们有临床试验数据。以前关于饮食和营养的研究表明，欧米茄-3（？3)脂肪酸对情绪有有益的影响，这可能为患有BP-NOS的儿童提供比目前可用的药物干预更有利的风险：效益比的初级或后续治疗。心理教育心理疗法（PEP）也显示出治疗8-12岁儿童双相谱系障碍的前景（弗里斯塔德，2006;弗里斯塔德，Verducci，Walters，& Young，2009）;其治疗BP-NOS的疗效尚未确定。目前的研究比较？3，PEP，和他们的组合，安慰剂补充剂和主动监测（AM）在一个为期12周的试验60名儿童BP-NOS（15个每个？3，？3加PEP、PEP和安慰剂，均进行主动监测）。主要目标是确定：1）可行性a）招募60名参与者在2年内; B）参与者保留超过12周的试验;和2）安慰剂对照效应量？3、PEP和联合治疗躁狂抑郁症状。次要目标是探索随时间变化的反应曲线、介质和调节剂、广泛结果变量的治疗反应、治疗依从性、对通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。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。这项试点研究？3、PEP， 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.