不同起始剂量米那普仑治疗抑郁症的有效性和安全性
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摘要
目的比较米那普仑25 mg·d~(-1)起始剂量治疗抑郁症的疗效和安全性是否非劣于50 mg·d~(-1)起始剂量。方法采用多中心、随机、双盲、平行对照、非劣效临床试验设计。纳入符合研究标准的抑郁症患者,随机均分为两组,试验组患者给予米那普仑25 mg·d~(-1)起始,逐渐增加到100 mg·d~(-1);对照组患者给予米那普仑50 mg·d~(-1)起始,逐渐增加到100 mg·d~(-1)。试验周期共6周,主要疗效指标为6周末17项汉密尔顿抑郁量表(HAMD-17)相对于基线的减分值。结果共纳入180例患者,用药6周末, FAS和PPS中试验组和对照组HAMD-17评分相对于基线减分值的组间差异的校正均数(95%可信区间)分别为-1.91 (-4.17～0.34)和0.32 (-1.43～2.07),区间上限低于预先设置的δ=2.5的非劣效界值,试验组非劣于对照组(P=0.095, P=0.721)。两组患者在用药后2周及6周不良事件及不良反应的发生率均无显著差异(P> 0.05)。结论米那普仑25 mg·d~(-1)起始剂量治疗抑郁症的疗效非劣于50 mg·d~(-1)起始剂量。
AIM To compare the efficacy and safety of milnacipran 25 mg·d~(-1) initial dose in the treatment of patients with major depressive disorder(MDD) is not inferior to the 50 mg·d~(-1) initial dose.METHODS A multicenter,randomized,double-blind,parallel-controlled,non-inferior clinical trial design was used in this study.Patients with MDD following inclusion criteria were randomly allocated to two groups equally.Low initial-dose group received milnacipran regimen with an initial dose of 25 mg·d~(-1),gradually increased to 100 mg·d~(-1).High initial-dose group started with an initial dose of 50 mg·d~(-1),gradually increased to100 mg·d~(-1).All patients at both groups would receive a stable,indicated dose of 100 mg·d~(-1) until week 6(42 days).The primary endpoint was the reduction of total score of Hamilton Depression Scale 17-item(HAMD-17)from baseline to week 6.RESULTS A total of 180 patients were enrolled.At 6 weeks of treatment,the mean changes(95% confidence interval) for the difference of total score reduction of HAMD-17 from baseline to week 6 in the low initial-dose group and high initial-dose group were-1.91(-4.17-0.34) and 0.32(-1.43-2.07) with FAS analysis and PPS analysis respectively,which lower than designed non-inferiority value of 2.5,meaning a statistically non-inferiority(P = 0.095,P = 0.721).There were no significant differences in the incidence of adverse events and adverse reactions between the two group at 2 and 6 weeks(all P > 0.05).CONCLUSION The treatment of milnacipran 25 mg·d~(-1) initial dose is not inferior to the 50 mg·d~(-1) initial dose in the treatment of MDD.
AIM To compare the efficacy and safety of milnacipran 25 mg·d~(-1) initial dose in the treatment of patients with major depressive disorder(MDD) is not inferior to the 50 mg·d~(-1) initial dose.METHODS A multicenter,randomized,double-blind,parallel-controlled,non-inferior clinical trial design was used in this study.Patients with MDD following inclusion criteria were randomly allocated to two groups equally.Low initial-dose group received milnacipran regimen with an initial dose of 25 mg·d~(-1),gradually increased to 100 mg·d~(-1).High initial-dose group started with an initial dose of 50 mg·d~(-1),gradually increased to100 mg·d~(-1).All patients at both groups would receive a stable,indicated dose of 100 mg·d~(-1) until week 6(42 days).The primary endpoint was the reduction of total score of Hamilton Depression Scale 17-item(HAMD-17)from baseline to week 6.RESULTS A total of 180 patients were enrolled.At 6 weeks of treatment,the mean changes(95% confidence interval) for the difference of total score reduction of HAMD-17 from baseline to week 6 in the low initial-dose group and high initial-dose group were-1.91(-4.17-0.34) and 0.32(-1.43-2.07) with FAS analysis and PPS analysis respectively,which lower than designed non-inferiority value of 2.5,meaning a statistically non-inferiority(P = 0.095,P = 0.721).There were no significant differences in the incidence of adverse events and adverse reactions between the two group at 2 and 6 weeks(all P > 0.05).CONCLUSION The treatment of milnacipran 25 mg·d~(-1) initial dose is not inferior to the 50 mg·d~(-1) initial dose in the treatment of MDD.
引文
[1]牛雅娟.《中国抑郁障碍防治指南》药物治疗解读[J].临床药物治疗杂志,2018,16(5):6-8.
[2]胡昌清,朱雪泉,丰雷,等.中国抑郁障碍防治指南(第二版)解读:药物治疗原则[J].中华精神科杂志,2017,50(3):172-174.
[3]LEE WK,AU YEUNG KL,LAM HB,et al.Consensus statements on the clinical understanding and use of milnacipran in Hong Kong[J].Hum Psychopharmacol,2018,33(2):e2651.
[4]SZEGEDI A,KOHNEN R,DIENEL A,et al.Acute treatment of moderate to severe depression with hypericum extract WS5570(St John's wort):randomised controlled double blind noninferiority trial versus paroxetine[J].BMJ,2005,330(7490):503.
[5]RUAN CJ,LI AN,DONG F,et al.Single-and multiple-dose milnacipran pharmacokinetics in healthy Han Chinese volunteers[J].Clin Pharmacokinet,2016,55(7):889-896.
[6]SUGAWARA Y,HIGUCHI H,YOSHIDA K,et al.Response rate obtained using milnacipran depending on the severity of depression in the treatment of major depressive patients[J].Clin Neuropharmacol,2006,29(1):6-9.
[7]ANSSEAU M,FRENCKELL RV,MERTENS C,et al.Controlled comparison of two doses of milnacipran(F 2207)and amitriptyline in major depressive inpatients[J].Psychopharmacology(Berl),1989,98(2):163-168.
[8]李华芳,武春艳,许秀峰,等.盐酸米那普仑与氟西汀治疗中国抑郁症的疗效和安全性比较(英文)[J].中国新药与临床杂志,2011,30(12):895-901.
[2]胡昌清,朱雪泉,丰雷,等.中国抑郁障碍防治指南(第二版)解读:药物治疗原则[J].中华精神科杂志,2017,50(3):172-174.
[3]LEE WK,AU YEUNG KL,LAM HB,et al.Consensus statements on the clinical understanding and use of milnacipran in Hong Kong[J].Hum Psychopharmacol,2018,33(2):e2651.
[4]SZEGEDI A,KOHNEN R,DIENEL A,et al.Acute treatment of moderate to severe depression with hypericum extract WS5570(St John's wort):randomised controlled double blind noninferiority trial versus paroxetine[J].BMJ,2005,330(7490):503.
[5]RUAN CJ,LI AN,DONG F,et al.Single-and multiple-dose milnacipran pharmacokinetics in healthy Han Chinese volunteers[J].Clin Pharmacokinet,2016,55(7):889-896.
[6]SUGAWARA Y,HIGUCHI H,YOSHIDA K,et al.Response rate obtained using milnacipran depending on the severity of depression in the treatment of major depressive patients[J].Clin Neuropharmacol,2006,29(1):6-9.
[7]ANSSEAU M,FRENCKELL RV,MERTENS C,et al.Controlled comparison of two doses of milnacipran(F 2207)and amitriptyline in major depressive inpatients[J].Psychopharmacology(Berl),1989,98(2):163-168.
[8]李华芳,武春艳,许秀峰,等.盐酸米那普仑与氟西汀治疗中国抑郁症的疗效和安全性比较(英文)[J].中国新药与临床杂志,2011,30(12):895-901.