Atlanta Center for Medical Research, Atlanta, Georgia 30308, USA.
Clin Ther. 2012 Nov;34(11):2202-11. doi: 10.1016/j.clinthera.2012.09.002. Epub 2012 Oct 8.
A human-volunteer study reported lower sedation intensity during escalation of the extended-release formulation of quetiapine fumarate (quetiapine XR) than the immediate-release (IR) formulation.
To test the hypothesis that the profile of initial tolerability, including sedation, differs between the extended-release (XR) and immediate-release (IR) formulations of quetiapine in patients with bipolar depression.
In a randomized, double-blind, double-dummy, parallel-group, Phase IV study, male and female inpatients aged 18 to 50 years with a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnosis of bipolar I or II depression were randomized after washout to receive placebo on day 1 and quetiapine XR or IR at escalating doses of 50, 100, 200, 300, and 300 mg once daily on the evenings of days 2 to 6, with hospital discharge on day 7. Sedation intensity was assessed by a self-reported modified Bond-Lader visual analog scale (VAS) score.
Of 139 randomized patients, 134 completed the study. Mean patient age was 39.0 years; mean weight, 91.3 kg; and mean body mass index (calculated as weight in kilograms divided by height in meters squared), 31.0. Sedation intensity 1 hour after administration of the 50-mg dose (the primary study measure) was statistically significantly lower with quetiapine XR versus IR (mean [SD] VAS score: 33.4 [26.92] vs 44.0 [31.76]; least squares mean difference: 12.55, P = 0.009; modified intention-to-treat population). Sedation intensity was found in secondary analyses to be significantly lower with quetiapine XR than with quetiapine IR 1, 2, and 3 hours after each dose on days 2 to 6 (P ≤ 0.05), with similar sedation intensity between the treatment groups 4 to 14 hours postdose. Rates of treatment-related adverse events were 47.1% with quetiapine XR versus 59.4% with quetiapine IR. Three serious adverse events (4.3%) occurred in the quetiapine XR group. Adverse events led to study discontinuation in 1 patient (1.4%) in the quetiapine XR group and in 2 patients (2.9%) in the IR group.
During the initial dose-escalation period studied, patients with bipolar depression reported statistically significantly lower sedation intensity in the 1 to 3 hours after taking quetiapine XR compared with the IR formulation. Overall tolerability for both formulations was consistent with the known profile of quetiapine. ClinicalTrials.gov identifier: NCT00926393.
一项志愿者人体研究报告称，富马酸喹硫平缓释片（喹硫平 XR）在递增剂量时的镇静强度低于其即释片（IR）。
验证富马酸喹硫平 XR 和 IR 治疗双相抑郁患者时，初始耐受性（包括镇静）谱是否存在差异的假设。
这是一项随机、双盲、双模拟、平行分组的 IV 期研究，入组年龄 18 至 50 岁、符合《精神障碍诊断与统计手册（第四版修订版）》（DSM-IV-TR）双相 I 或 II 型抑郁诊断的男性和女性住院患者在洗脱期后随机分组，第 1 天接受安慰剂，第 2 至 6 天晚上接受递增剂量的 50、100、200、300 和 300mg 富马酸喹硫平 XR 或 IR，第 7 天出院。镇静强度采用改良的 Bond-Lader 视觉模拟量表（VAS）评分进行自我报告评估。
139 例随机患者中，134 例完成了研究。患者平均年龄为 39.0 岁，平均体重为 91.3kg，平均体重指数（BMI，体重以千克为单位，身高以米为单位）为 31.0。第 50mg 剂量给药后 1 小时（主要研究指标）的镇静强度，与富马酸喹硫平 XR 相比，IR 组显著升高（平均[SD]VAS 评分：33.4[26.92] vs 44.0[31.76]；最小二乘均值差：12.55，P=0.009；意向治疗人群）。在次要分析中发现，与富马酸喹硫平 IR 相比，富马酸喹硫平 XR 在第 2 至 6 天的每天晚上每个剂量后 1、2 和 3 小时的镇静强度显著降低（P≤0.05），两组在给药后 4 至 14 小时的镇静强度相似。富马酸喹硫平 XR 组和富马酸喹硫平 IR 组的治疗相关不良事件发生率分别为 47.1%和 59.4%。富马酸喹硫平 XR 组有 3 例严重不良事件（4.3%），IR 组有 2 例（2.9%）。不良事件导致 1 例（1.4%）患者和 2 例（2.9%）患者分别停止接受富马酸喹硫平 XR 和 IR 治疗。
在研究的初始剂量递增期间，与富马酸喹硫平 IR 相比，双相抑郁患者在服用富马酸喹硫平 XR 后 1 至 3 小时报告的镇静强度显著降低。两种制剂的总体耐受性与喹硫平的已知特征一致。临床试验注册编号：NCT00926393。
