Stewart Donna E, Wohlreich Madelaine M, Mallinckrodt Craig H, Watkin John G, Kornstein Susan G
University Health Network, University of Toronto, Ontario, Canada.
J Affect Disord. 2006 Aug;94(1-3):183-9. doi: 10.1016/j.jad.2006.04.006. Epub 2006 Jun 14.
While some studies have suggested sex differences in the efficacy of antidepressant medications, there have been few investigations into potential sex differences related to safety and/or tolerability. Pooled data from double-blind, placebo-controlled studies were utilized to assess the safety and tolerability of duloxetine in the treatment of major depressive disorder (MDD) in male and female patients.
Safety data were pooled from seven double-blind, placebo-controlled clinical trials of duloxetine. Patients (aged >or=18 years) meeting DSM-IV criteria for MDD received duloxetine (40-120 mg/day, male: N=318, female: N=578) or placebo (male: N=242, female: N=484) for up to 9 weeks. Safety was assessed using discontinuation rates, spontaneously reported treatment-emergent adverse events, changes in vital signs and laboratory analyses.
Discontinuation rates due to adverse events among duloxetine-treated patients were 18.6% for males and 13.5% for females. The most common treatment-emergent adverse events in both male and female patients included nausea, headache, dry mouth, diarrhea and constipation. The only event occurring at significantly different rates in male and female patients was nausea (Breslow Day p-value=0.008), and the significant difference was driven by a placebo nausea rate that was almost three times greater in females compared with males. No significant differential sex effects were found for pulse, blood pressure or weight. No laboratory analyte had an incidence of abnormal high or low values that differed significantly between male and female patients.
This was a post-hoc analysis of pooled data from acute phase clinical trials. Plasma concentrations of duloxetine were not obtained. Adverse event rates were based on spontaneous reports and differential dose-response effects were not evaluated.
No evidence of clinically meaningful sex differences in the safety and tolerability of duloxetine were uncovered.
虽然一些研究表明抗抑郁药物疗效存在性别差异，但很少有关于安全性和/或耐受性方面潜在性别差异的调查。利用双盲、安慰剂对照研究的汇总数据来评估度洛西汀治疗男性和女性重度抑郁症（MDD）的安全性和耐受性。
安全性数据来自七项度洛西汀的双盲、安慰剂对照临床试验。符合DSM-IV标准的MDD患者（年龄≥18岁）接受度洛西汀（40 - 120毫克/天，男性：N = 318，女性：N = 578）或安慰剂（男性：N = 242，女性：N = 484）治疗长达9周。通过停药率、自发报告的治疗中出现的不良事件、生命体征变化和实验室分析来评估安全性。
度洛西汀治疗患者中因不良事件导致的停药率男性为18.6%，女性为13.5%。男性和女性患者中最常见的治疗中出现的不良事件包括恶心、头痛、口干、腹泻和便秘。男性和女性患者中发生率有显著差异的唯一事件是恶心（Breslow Day p值 = 0.008），且这种显著差异是由女性安慰剂恶心率几乎是男性的三倍所驱动。在脉搏、血压或体重方面未发现显著的性别差异。在实验室分析物中，男性和女性患者之间异常高值或低值的发生率没有显著差异。
这是对急性期临床试验汇总数据的事后分析。未获取度洛西汀的血浆浓度。不良事件发生率基于自发报告，未评估剂量反应差异效应。
未发现度洛西汀在安全性和耐受性方面存在具有临床意义的性别差异的证据。
