PDF(Pubmed)
Abstract：
Inadequate response to antipsychotic treatment is common in patients with schizophrenia. This study evaluated pimavanserin, a 5-HT 2A receptor inverse agonist/antagonist, as adjunctive treatment in patients with inadequate response. This was a 6-week, randomized, double-blind, placebo-controlled, study conducted in North America and Europe. Adult outpatients with schizophrenia and inadequate response to current antipsychotic were enrolled. Inclusion criteria included Positive and Negative Syndrome Scale (PANSS) total score ≥65 and ≤110 and retrospective antipsychotic treatment stability of 8 weeks. Pimavanserin 20 mg/day or placebo added to ongoing antipsychotic was tested in a flexible-dose paradigm with dose adjustments allowed during the first 3 weeks. The primary efficacy endpoint, PANSS total score change from baseline to week 6, was not met, although improvement was greater with pimavanserin than placebo (LS mean difference: -2.1, [95% CI: -4.5, 0.4]; P = .094). As a hierarchical testing procedure was used, additional efficacy analyses were exploratory. Clear separation from placebo was observed with pimavanserin at week 6 for the PANSS Negative Symptoms subscale (LS mean difference: -0.7, [95% CI: -1.5, 0.0]) and Marder Negative Symptom Factor score (-0.9, [-1.7, -0.1]). Analysis of European sites (81.5% of patients) revealed a difference for pimavanserin versus placebo on PANSS total score (LS mean difference: -3.1, [95% CI: -5.8, -0.4]) and Clinical Global Impressions-Severity score (-0.2, [-0.4, -0.0]). Treatment-emergent adverse events occurred in 39.9% with pimavanserin and 36.4% with placebo. Although statistical significance for the primary endpoint was not met, a trend toward improvement in negative symptoms was observed with pimavanserin, warranting further study.
摘要：
抗精神病药物治疗反应不足在精神分裂症患者中很常见。这项研究评估了匹马色林，5-HT2A受体反向激动剂/拮抗剂，作为反应不足的患者的辅助治疗。这是一个6周,随机化，双盲,安慰剂对照,在北美和欧洲进行的研究。招募了患有精神分裂症和对当前抗精神病药反应不足的成年门诊患者。纳入标准包括阳性和阴性综合征量表（PANSS）总分≥65和≤110，回顾性抗精神病药物治疗稳定8周。在灵活的剂量范例中测试了向正在进行的抗精神病药添加的匹马舍林20mg/天或安慰剂，并在前3周内允许剂量调整。主要疗效终点，PANSS总分从基线到第6周的变化，未达到，尽管与安慰剂相比,吡马色林的改善更大(LS平均差异:-2.1,[95%CI:-4.5,0.4];P=0.094).由于使用了分层测试程序，额外的疗效分析是探索性的.在第6周，PANSS阴性症状子量表（LS平均差：-0.7，[95％CI：-1.5，0.0]）和Marder阴性症状因子评分（-0.9，[-1.7，-0.1]）与pimavanserin明显分离。对欧洲站点（81.5％的患者）的分析显示，pimavanserin与安慰剂在PANSS总分（LS平均差异：-3.1，[95％CI：-5.8，-0.4]）和临床全球印象-严重程度评分（-0.2，[-0.4，-0.0]）上存在差异。吡马色林治疗引起的不良事件发生率为39.9%，安慰剂组发生率为36.4%。尽管未达到主要终点的统计学意义，吡马色林观察到阴性症状改善的趋势，值得进一步研究。
