Project 3 ACISR

青少年精神障碍是急性和长期的挑战，包括鉴别诊断、预后和治疗选择（Kafantaris等人，1996，1998）。当锂在美国广泛使用时，对具有精神病特征的心境障碍与精神分裂症的鉴别诊断给予了很多关注，因为对于某些患者，锂比第一代抗精神病药更有效（Janicak等，1992）。第二代抗精神病药（SGAs）已被证明是 作为单药治疗急性躁狂症有效（Perils et al. 2006），当与传统的心境稳定剂联合使用时，可提高应答率，包括在有或无精神病特征的青少年中（Del Bello et al. 2002）。在一项小型研究中，尽管正在接受锂治疗，但在研究入组时具有显著精神病特征的青少年似乎仍受益于持续抗精神病药物的连续治疗（Kafantaris et al. 2001 a，2001 b）。由于许多被批准用于双相情感障碍的治疗方法现在与用于精神分裂症的治疗方法趋同，因此准确诊断，特别是在青少年中，似乎不那么重要，并质疑是否有必要使用传统的情绪稳定剂治疗双相情感障碍。此外，尽管在一项成人研究中，在第一代抗精神病药中添加丙戊酸盐导致急性缓解率更高（Muller-Oerlinghausen et all 2000），但尚不清楚在SGA中添加传统情绪稳定剂是否有益于精神病性躁狂的急性和持续治疗。这是一个重要的问题，特别是对青少年，因为早期精神病发作的治疗对疾病的病程和发育结果有重要影响。 该研究是一项安慰剂对照、平行组、随机临床试验，比较两种治疗策略对躁狂和突出精神病特征的青少年的影响。一组将接受SGA和安慰剂，另一组将接受SGA和锂。在急性治疗阶段，在SGA中添加锂的可能益处包括更高比例的应答者，更短的应答时间和潜在的更低剂量的SGA。对于继续治疗，可能的好处包括预防抑郁症发作。本研究的结果将为更明确的试验设计提供信息。 具体目标是： 1.目的评价碳酸锂治疗青少年躁狂伴精神病性特征的疗效和安全性。 2.目的：通过6个月的随访，评估口服锂剂预防青少年精神病性情绪发作复发的有效性和安全性。

Psychotic disorders in adolescents present acute and long-term challenges, including those of differential diagnosis, prognosis and treatment choices (Kafantaris et al. 1996, 1998). When lithium became widely available in the U.S., much attention was paid to differential diagnosis of mood disorders with psychotic features from schizophrenia because, for some patients, lithium was more effective than first-generation antipsychotics (Janicak et al.1992). Second generation antipsychotics (SGAs) have been shown to be efficacious as monotherapy for the treatment of acute mania (Perils et al. 2006) and to increase response rates when added to a traditional mood stabilizer, including in adolescents with or without psychotic features (Del Bello et al. 2002). In a small study, adolescents who had prominent psychotic features at study entry appeared to benefit from continuing adjunctive treatment with an antipsychotic agent despite ongoing lithium treatment (Kafantaris et al. 2001a, 2001b). As many of the treatments approved for bipolar disorder now converge with those used for schizophrenia, pinpointing the exact diagnosis, particularly in adolescents, may seem less crucial and call into question whether treatment with traditional mood stabilizers for bipolar disorder with psychotic features is even necessary. Moreover, although the addition of valproate to a first-generation antipsychotic resulted in a higher acute response rate in one adult study (Muller-Oerlinghausen et all 2000), it is not known whether it is beneficial to add a traditional mood stabilizer to a SGA for acute and continuation the treatment of psychotic mania. This is an important question, particulariy for adolescents, as the treatment of an early psychotic episode has significant impact on course of illness and developmental outcome. The proposed study is a placebo-controlled, parallel group, randomized clinical trial comparing two treatment strategies in adolescents with mania and prominent psychotic features. One group will receive a SGA and placebo and the other will receive a SGA and lithium. During the acute treatment phase, the possible benefits of adding lithium to a SGA include a higher proportion of responders, shorter time to response, and potentially a lower dose of SGA. For continuation treatment, possible benefits include prophylaxis against episodes of depression. Results from this study will inform the design of a more definitive trial. Specific aims are: 1. To assess the efficacy and safety of adjunctive lithium in the acute treatment of mania with psychotic features in adolescents. 2. To assess the efficacy and safety of adjunctive lithium in the prophylaxis against recurrence of mood episodes with psychotic features in adolescents over a six month follow-up period.