Pritchett Yili L, Marciniak Martin D, Corey-Lisle Patricia K, Berzon Richard A, Desaiah Durisala, Detke Michael J
Eli Lilly and Company, Lilly Corporate Center, DC 6112, Indianapolis, IN 46285, USA.
J Psychiatr Res. 2007 Apr-Jun;41(3-4):311-8. doi: 10.1016/j.jpsychires.2006.06.013. Epub 2006 Aug 28.
At effective doses, patients with major depressive disorder (MDD) treated with duloxetine have been found to experience significant symptom improvement as measured by HAMD(17) total score. In addition, duloxetine-treated patients have significantly higher remission and response rates compared with placebo. The objective of this analysis is to determine the optimal dose of duloxetine in MDD.
Effect size for duloxetine 40mg, 60mg, 80mg, and 120mg per day were estimated using all 6 acute phase III clinical trials in patients with MDD. The tolerability of duloxetine 40mg, 60mg, 80mg, and 120mg were evaluated using pooled data from the 6 studies. The primary efficacy measure in all trials was the HAMD(17) total score, from which were determined the effect size for HAMD(17) change scores, response rates (50% reduction from baseline to endpoint), and remission rates (HAMD(17) total score < or =7).
A total of 1619 randomized patients were included in these studies, of which 632 were treated with placebo; 177 with duloxetine 40mg/day; 251 with 60mg/day; 363 with 80mg/day; and 196 with 120mg/day. An evaluation of increments in effect size between doses consistently showed that the most notable gain in effect size for efficacy was the 40-60mg/day dosage range. All dosages from 60 to 120mg were effective. The tolerability assessment indicated duloxetine at 40-120mg/day is well tolerated. Furthermore, the initial doses of 40-80mg/day were found to have comparable tolerability.
The effect size analyses demonstrate that duloxetine 40mg has minimum efficacy, and that duloxetine 60-120mg/day is effective in the treatment of patients with MDD. An initial dose less than 60mg/day might provide better tolerability for some patients diagnosed with MDD.
研究发现，接受度洛西汀治疗的重度抑郁症（MDD）患者在使用有效剂量时，通过汉密尔顿抑郁量表（HAMD）（17项）总分测量，症状有显著改善。此外，与安慰剂相比，接受度洛西汀治疗的患者缓解率和有效率显著更高。本分析的目的是确定度洛西汀治疗MDD的最佳剂量。
使用针对MDD患者的所有6项急性期III期临床试验，估计每日40mg、60mg、80mg和120mg度洛西汀的效应量。使用这6项研究的汇总数据评估40mg、60mg、80mg和120mg度洛西汀的耐受性。所有试验的主要疗效指标是HAMD（17项）总分，据此确定HAMD（17项）变化分数的效应量、有效率（从基线到终点降低50%）和缓解率（HAMD（17项）总分≤7）。
这些研究共纳入1619例随机分组患者，其中632例接受安慰剂治疗；177例接受每日40mg度洛西汀治疗；251例接受每日60mg治疗；363例接受每日80mg治疗；196例接受每日120mg治疗。对各剂量之间效应量增加的评估一致显示，疗效效应量最显著的增加是在每日40 - 60mg剂量范围内。60至120mg的所有剂量均有效。耐受性评估表明，每日40 - 120mg的度洛西汀耐受性良好。此外，发现每日40 - 80mg的初始剂量具有相当的耐受性。
效应量分析表明，40mg度洛西汀疗效最低，而每日60 - 120mg度洛西汀对MDD患者有效。对于一些诊断为MDD的患者，每日初始剂量低于60mg可能具有更好的耐受性。
