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) 的较温和版本，现在研究表明双相情感障碍 - 未另有说明 (BP-NOS) 是一种高度损害的疾病。最近在理解 BP-NOS 方面取得了相当大的进展，很大程度上是通过利用 BP-NOS 的明确操作定义进行的研究（参见 NIMH 资助的双相情感障碍青年课程和结果 [COBY] 和躁狂症状的纵向评估 [LAMS] 研究）。然而，临床试验主要针对患有 I 型双相情感障碍 (BP1) 的青少年。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 BP1 和 BP2 相似；它在功能障碍方面与 BP2 相似（Axelson 等，2006）。然而，患有 BP-NOS 的青少年的恢复速度比患有 BP1 或 BP2 的青少年慢三倍，并且情绪不稳定（Birmaher 等，2006）。与诊断为 BP1 和 BP2 的青少年相比，他们更有可能保持亚综合征状态，而不是变得无症状（Birmaher 等，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，与治疗患有 BP1 的青少年的风险：收益比相比，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，我们有针对这些青少年的临床试验数据。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影响，这可能为患有 BP-NOS 的儿童提供主要或辅助治疗，其风险：效益比比目前可用的药物干预措施更有利。心理教育心理治疗 (PEP) 在治疗 8-12 岁儿童双相谱系障碍方面也显示出前景（Fristad, 2006；Fristad, Verducci, Walters, & Young, 2009）；其具体治疗 BP-NOS 的功效尚未确定。目前的研究对 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（每 15 名儿童服用 ?3、?3 加 PEP、PEP 和安慰剂，均进行主动监测）。主要目标是确定： 1) a) 2 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； 2) β3、PEP 和联合治疗对躁狂和抑郁症状的安慰剂对照效应大小。次要目标是探索随着时间的推移的反应曲线、中介因素和调节因素、各种结果变量的治疗反应、治疗的依从性、对情绪稳定药物经常恶化的生理参数的影响，以及接受 3 和/或 PEP 的参与者的副作用经历。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提高所获得的知识。这项针对 ?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：儿童期发病的双相情感障碍（未另有说明）（BP-NOS）会造成严重损害。然而，并没有专门针对它设计的治疗指南；目前的临床实践以 BP1 的治疗为指导。目前可用治疗方法的局限性促使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) 取得了有希望但非决定性的初步结果。这项小型随机对照研究将探讨研究 β3 膳食补充剂、PEP 和联合治疗对减少诊断为 BP-NOS 的儿童抑郁和躁狂症状的影响的可行性。通过将结果与针对抑郁症儿童的平行研究的结果进行比较，可以最大限度地了解知识。

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.