:Background:Early-onset schizophrenia is characterized by greater severity and more functional impairment than adult-onset schizophrenia. Few studies have prospectively evaluated short- or long-term antipsychotic efficacy in treatment-naïve (vs. previously treated) first-episode schizophrenia. The aim of this post-hoc analysis was to evaluate the long-term efficacy of lurasidone in antipsychotic-naïve adolescents with schizophrenia.Method:Patients aged 13-17 years with schizophrenia were randomized to 6 weeks of double-blind (DB), fixed-dose treatment with lurasidone (40 mg/day or 80 mg/day) or placebo. Six-week completers were eligible to enroll in an open-label (OL), flexible dose 2-year lurasidone treatment study. Efficacy over 104 weeks of OL treatment with lurasidone was evaluated for 2 patient groups based on treatment status prior to entering the initial DB study (treatment-naïve [TN] vs. treated previously [TP]). Treatment-naïve was defined as never having received antipsychotic treatment prior to randomization. Efficacy measures included the PANSS total score and the Clinical Global Impressions-Severity (CGI-S) score. Treatment response was defined as ≥20% reduction from baseline in PANSS total score.Results:A total of 50 TN and 221 TP patients completed the 6-week DB study and entered the extension study; and 30 (60.0%) TN and 126 (57.0%) TP patients completed 104 weeks. In the ITT population of the initial DB study, treatment with lurasidone (vs. placebo) yielded larger effects at DB endpoint on the PANSS total score in the TN group (-25.0 vs. -14.4; P<0.02; effect size [ES]=0.75) compared to the TP group (-17.3 vs. -10.0; P<0.001; ES=0.45); and in the CGI-S score in the TN group (-1.07 vs. -0.28; P=0.002; ES=0.97) compared to the TP group (-0.91 vs. -0.55; P=0.005; ES=0.38). During OL treatment with lurasidone, the magnitude of improvement from DB baseline continued to be somewhat larger in the PANSS total score for TN patients (n=38) vs. TP patients (151) at week 52 (-32.6 vs. -28.1) and week 104 (-33.6 vs. -29.2); and in the CGI-S score for TN vs. TP patients at week 52 (-2.1 vs. -1.5) and week 104 (-2.1 vs. -1.6). Responder rates during treatment with lurasidone were 72.0% (TN group) and 61.1% (TP group) at OL baseline (number-needed-to-treat [NNT]=10), 100% and 90.1% at week 52 [NNT=11], and 100% and 88.9% at week 104 [NNT=11]. During OL treatment, the most common adverse events for TN vs. TP patients were headache (26.0% vs. 23.5%), nasopharyngitis (24.0% vs. 5.4%), nausea (16.0% vs. 11.8%), and dizziness (16.0% vs. 4.1%).Conclusion:In this post-hoc analysis of a 2-year OL extension study, antipsychotic-naïve adolescents with schizophrenia responded well to treatment with lurasidone at doses of 40 mg/day or 80 mg/day. TN patients achieved greater improvement than TP patients during acute treatment; and these greater treatment effects were largely maintained during 2 years of continued treatment with lurasidone.Funding Acknowledgements:Supported by funding from Sunovion Pharmaceuticals Inc

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104 鲁拉西酮对未使用抗精神病药物与使用抗精神病药物治疗的精神分裂症青少年的长期疗效：一项为期两年的研究分析

：背景：早发性精神分裂症的特点是比成人精神分裂症更严重，功能障碍更多。很少有研究前瞻性地评估了治疗初治（与先前治疗过的）首发精神分裂症的短期或长期抗精神病药疗效。这项事后分析的目的是评估鲁拉西酮对未使用抗精神病药物的青少年精神分裂症的长期疗效。方法：将 13-17 岁的精神分裂症患者随机分配至 6 周的双盲 (DB)，固定- 使用鲁拉西酮（40 毫克/天或 80 毫克/天）或安慰剂进行剂量治疗。六周完成者有资格参加一项开放标签 (OL)、灵活剂量的 2 年鲁拉西酮治疗研究。根据进入初始 DB 研究之前的治疗状态（初治 [TN] 与之前治疗 [TP]），对 2 个患者组使用鲁拉西酮进行 104 周的 OL 治疗的疗效进行了评估。初治被定义为在随机化之前从未接受过抗精神病药物治疗。疗效指标包括 PANSS 总分和临床总体印象-严重性 (CGI-S) 评分。治疗反应定义为PANSS总分较基线降低≥20%。 结果：共有50名TN和221名TP患者完成了为期6周的DB研究并进入扩展研究；30 名 (60.0%) TN 和 126 (57.0%) 名 TP 患者完成了 104 周。在初始 DB 研究的 ITT 人群中，鲁拉西酮治疗（与安慰剂相比）在 DB 终点对 TN 组的 PANSS 总分产生更大的影响（-25.0 与 -14. 4；P<0.02；效应量 [ES]=0.75）与 TP 组相比（-17.3 对 -10.0；P<0.001；ES=0.45）；与 TP 组相比，TN 组的 CGI-S 评分（-1.07 对 -0.28；P=0.002；ES=0.97）（-0.91 对 -0.55；P=0.005；ES=0.38）。在使用 lurasidone 进行 OL 治疗期间，在第 52 周（-32.6 对 -28.1）和第 104 周（-33.6 对 -29.2）；在第 52 周（-2.1 对 -1.5）和第 104 周（-2.1 对 -1.6）的 TN 与 TP 患者的 CGI-S 评分中。lurasidone 治疗期间的应答率为 72.0%（TN 组）和 61.1%（TP 组）在 OL 基线（需要治疗的人数 [NNT]=10），在第 52 周时分别​​为 100% 和 90.1% [NNT=11 ]，在第 104 周时分别​​为 100% 和 88.9% [NNT=11]。OL治疗期间，TN 与 TP 患者最常见的不良事件是头痛（26.0% 对 23.5%）、鼻咽炎（24.0% 对 5.4%）、恶心（16.0% 对 11.8%）和头晕（16.0% 对 4.1%） %). 结论：在这项为期 2 年的 OL 扩展研究的事后分析中，未使用抗精神病药物的精神分裂症青少年对 40 毫克/天或 80 毫克/天的鲁拉西酮治疗反应良好。TN患者在急性治疗期间比TP患者取得更大的改善；在持续使用鲁拉西酮治疗 2 年期间，这些更大的治疗效果在很大程度上得以维持。资金致谢：由 Sunovion Pharmaceuticals Inc. 提供资金支持 在这项为期 2 年的 OL 扩展研究的事后分析中，未使用抗精神病药物的精神分裂症青少年对 40 毫克/天或 80 毫克/天的鲁拉西酮治疗反应良好。TN患者在急性治疗期间比TP患者取得更大的改善；在持续使用鲁拉西酮治疗 2 年期间，这些更大的治疗效果在很大程度上得以维持。资金致谢：由 Sunovion Pharmaceuticals Inc. 提供资金支持 在这项为期 2 年的 OL 扩展研究的事后分析中，未使用抗精神病药物的精神分裂症青少年对 40 毫克/天或 80 毫克/天的鲁拉西酮治疗反应良好。TN患者在急性治疗期间比TP患者取得更大的改善；在持续使用鲁拉西酮治疗的 2 年期间，这些更大的治疗效果在很大程度上得以维持。资金致谢：由 Sunovion Pharmaceuticals Inc. 提供资金支持