一项评估匹莫范色林辅助治疗对治疗反应不足的重性抑郁障碍患者的疗效和安全性的 2 期、随机、双盲、安慰剂对照研究（CLARITY）。

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Adjunctive Pimavanserin in Patients With Major Depressive Disorder and an Inadequate Response to Therapy (CLARITY).

机构信息

Department of Psychiatry, Harvard Medical School, 55 Fruit St, Bulfinch 351, Boston, MA 02114.

Department of Psychiatry, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts, USA.

出版信息

J Clin Psychiatry. 2019 Sep 24;80(6):19m12928. doi: 10.4088/JCP.19m12928.

DOI:10.4088/JCP.19m12928

PMID:31556975

Abstract

OBJECTIVE

Pimavanserin is a 5-hydroxytryptamine-2A antagonist and inverse receptor agonist. This phase 2 study examined the efficacy and safety of pimavanserin as adjunctive therapy in patients with major depressive disorder (MDD).

METHODS

This was a multicenter, randomized, double-blind, placebo-controlled study in patients with DSM-5-defined MDD and an inadequate response to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). Using a 2-stage sequential parallel-comparison design, patients were initially randomized in a 3:1 ratio to placebo or pimavanserin added to ongoing SSRI or SNRI therapy; at 5 weeks, placebo nonresponders were re-randomized to placebo or pimavanserin for an additional 5 weeks. Key endpoints were change from baseline to the end of each stage in 17-item Hamilton Depression Rating Scale (HDRS-17) total score and Sheehan Disability Scale (SDS) score.

RESULTS

Between December 2016 and October 2018, 207 patients were randomized. For the prespecified pooled Sequential Parallel Comparison Design analyses of Stages 1 and 2, the least squares (LS) mean (SE) difference for the HDRS-17 total score was -1.7 (0.85) (P = .039) and for the SDS score was -0.8 (0.29) (P = .004). At week 5 of Stage 1, LS mean (SE) difference for pimavanserin versus placebo was significant for changes on the HDRS-17 (-4.0 [1.09], P = .0003) and SDS (-1.2 [0.40], P = .0036) with effect sizes of 0.626 and 0.498, respectively. Early and sustained separation of pimavanserin from placebo (P < .05) occurred at 1 week. The most common adverse events with pimavanserin were dry mouth, nausea, and headache.

CONCLUSIONS

Pimavanserin demonstrated robust efficacy in patients with MDD and an inadequate response to an SSRI or SNRI. Tolerability was consistent with previous experience.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT03018340.

摘要

目的

匹莫范色林是一种 5-羟色胺 2A 拮抗剂和反向受体激动剂。这项 2 期研究考察了匹莫范色林作为辅助治疗对伴有抑郁障碍（MDD）的患者的疗效和安全性。

方法

这是一项多中心、随机、双盲、安慰剂对照的研究，纳入了符合 DSM-5 定义的 MDD 患者，这些患者对选择性 5-羟色胺再摄取抑制剂（SSRI）或 5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRI）治疗反应不足。采用两阶段序贯平行比较设计，患者最初以 3:1 的比例随机分配至安慰剂或匹莫范色林联合正在进行的 SSRI 或 SNRI 治疗；在第 5 周时，安慰剂无应答者被重新随机分配至安慰剂或匹莫范色林治疗，为期 5 周。主要终点是 17 项汉密尔顿抑郁评定量表（HDRS-17）总分和 Sheehan 残疾量表（SDS）评分从基线到各阶段结束的变化。

结果

2016 年 12 月至 2018 年 10 月期间，共有 207 名患者被随机分配。对于第 1 阶段和第 2 阶段的预设序贯平行比较设计分析，匹莫范色林治疗的最小二乘（LS）均值（SE）差值在 HDRS-17 总分方面为-1.7（0.85）（P=0.039），在 SDS 评分方面为-0.8（0.29）（P=0.004）。在第 1 阶段第 5 周，匹莫范色林与安慰剂相比，HDRS-17 （-4.0[1.09]，P=0.0003）和 SDS （-1.2[0.40]，P=0.0036）的变化有显著差异，效应大小分别为 0.626 和 0.498。匹莫范色林与安慰剂的早期和持续分离（P<0.05）发生在第 1 周。匹莫范色林最常见的不良反应是口干、恶心和头痛。