BackgroundBipolar disorder frequently has an early onset, with an estimated 1.8% prevalence of bipolar I disorder in children and adolescents. Childhood onset of bipolar disorder is typically associated with a chronic, severe, and disabling course of illness. Relatively few prospective studies are available that evaluate the long-term efficacy of atypical antipsychotics in achieving and sustaining response or remission in pediatric patients with bipolar depression. Lurasidone has been approved by the FDA as monotherapy for bipolar depression in pediatric patients ages 10–17 years. The aim of the current post-hoc analysis was to evaluate the long-term efficacy of lurasidone in achieving response or remission in children and adolescents with bipolar depression followed over a two-year period.MethodPatients 10–17 years with bipolar I depression who completed a 6-week double-blind (DB) study of lurasidone vs. placebo were eligible to enroll in a two-year, open-label (OL) extension study in which patients were continued on flexibly-dosed lurasidone (20–80 mg/d) or switched from placebo to lurasidone. Efficacy measures included the Children’s Depression Rating Scale, Revised (CDRS-R) and the Clinical Global Impression, Bipolar Depression Severity scale (CGI-BP-S). Functioning was evaluated utilizing the Clinician-rated Children’s Global Assessment Scale (CGAS) score, with a score >70 indicating no clinically meaningful functional impairment. Responder criteria were met if a patient achieved criteria = 50% reduction from DB baseline in the CDRS-R total score: remission criteria were met if a patient achieved a CDRS-R Total Score =28 and a YMRS total score =8 and CGI-BP-S depression score =3, and a patient was considered to have met recovery criteria if they achieved remission with a CGAS score >70. In addition, a more stringent outcome, sustained remission, was also analyzed, which required a patient to meet remission criteria for =24 consecutive weeks.ResultsA total of 306 patients completed the 6-week DB study and entered the extension study; 195 (63.7%) patients completed one year of treatment and 168 (54.9%) patients completed two years of treatment. Responder rates at OL baseline, one year, and two years were: 51.0%, 88.4% and 91.1%, respectively; remission rates were 24.3%, 61.3%, and 75.6%, respectively; and recovery rates were 17.7%, 53.8%, and 73.8%. On a Pearson correlation analysis, there was a strong inverse relationship (r = −0.71) between CDRS-R total score, and global functioning as measured by the CGAS. Sustained remission was achieved by 37.2% of patients at one year and 57% of patients after two years.ConclusionsIn children and adolescents with bipolar depression, up to 2 years of treatment with lurasidone was associated with continued improvement in depressive symptoms, resulting in progressively higher rates of response, remission, recovery, and the more rigorously calculated outcome of sustained remission.FundingSunovion Pharmaceuticals Inc.

中文翻译：

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鲁拉西酮在小儿双相抑郁症中的长期疗效：反应、缓解和恢复

背景双相情感障碍通常早发，儿童和青少年双相 I 型障碍的患病率估计为 1.8%。双相情感障碍的儿童期发病通常与慢性、严重和致残的疾病过程有关。相对较少的前瞻性研究可评估非典型抗精神病药物在儿童双相抑郁症患者中实现和维持缓解或缓解的长期疗效。Lurasidone 已被 FDA 批准作为 10-17 岁儿童双相抑郁症的单一疗法。当前事后分析的目的是评估鲁拉西酮在两年内随访的双相抑郁儿童和青少年中实现缓解或缓解的长期疗效。方法 10-17 岁双相 I 型抑郁症患者完成了为期 6 周的鲁拉西酮与安慰剂双盲 (DB) 研究，有资格参加为期两年的开放标签 (OL) 扩展研究，患者继续参与该研究使用灵活剂量的鲁拉西酮（20-80 毫克/天）或从安慰剂转换为鲁拉西酮。疗效测量包括儿童抑郁评定量表修订版 (CDRS-R) 和临床总体印象双相抑郁严重程度量表 (CGI-BP-S)。使用临床医生评定的儿童全球评估量表 (CGAS) 评分评估功能，评分 > 70 表示没有临床意义的功能障碍。如果患者达到标准 = CDRS-R 总分从 DB 基线降低 50%，则满足响应者标准：如果患者达到 CDRS-R 总分 =28、YMRS 总分 =8 和 CGI​​-BP-S 抑郁评分 =3，则满足缓解标准，如果患者达到缓解并达到CGAS 评分 >70。此外，还分析了一个更严格的结果，即持续缓解，这需要患者连续=24周达到缓解标准。结果共有306名患者完成了为期6周的DB研究并进入了扩展研究；195 名（63.7%）患者完成了一年的治疗，168 名（54.9%）患者完成了两年的治疗。OL 基线、一年和两年的应答率分别为：51.0%、88.4% 和 91.1%；缓解率分别为 24.3%、61.3% 和 75.6%；回收率分别为17.7%、53.8%和73.8%。在 Pearson 相关分析中，CDRS-R 总分与 CGAS 测量的全局功能之间存在很强的反比关系（r = -0.71）。37.2% 的患者在一年内获得持续缓解，57% 的患者在两年后获得持续缓解。结论在患有双相抑郁症的儿童和青少年中，长达 2 年的鲁拉西酮治疗与抑郁症状的持续改善有关，导致抑郁症状逐渐升高缓解率、缓解率、恢复率以及更严格计算的持续缓解结果。资金来源 Sunovion Pharmaceuticals Inc.