Bipolar drug development: are we getting closer to the real world?
Bipolar drug development: are we getting closer to the real world?
复制标题
双相药物开发：我们离现实世界越来越近了吗？
DOI：
10.1176/appi.ajp.2008.08060967
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Kemp,DavidE
中科院分区：
文献类型：
--
作者：
Calabrese,JosephR;Kemp,DavidE
与既往将非典型抗精神病药与锂盐或丙戊酸盐联合使用的随机对照试验一致，根据杨氏躁狂量表总分的变化评估，连续6周阿立哌唑显著减轻了躁狂症状。然而，反映了研究者为尽量减少缺失数据所做的不懈努力，当阿立哌唑联合使用时，完成率高达79%，而单独使用锂或丙戊酸盐时，完成率为85%。尽管如此，在杨氏躁狂评定量表上比安慰剂降低2.6分表明阿立哌唑仅提供适度的疗效。虽然每例患者在进入随机化阶段前接受了至少2周的治疗性血清锂或丙戊酸盐，但未报告关于锂/丙戊酸盐使用持续时间的临床有用历史信息。此外，在被视为部分无应答的患者中，锂和丙戊酸盐的平均血药浓度分别为< 0.8 mmol/l和< 78 µg/ml。当面对具有相似血药浓度的部分反应性双相I型躁狂患者时，我们预计许多临床医生会在添加第二种药物之前进一步增加锂或丙戊酸盐的剂量。然而，关于锂的剂量和耐受性的新观点已经出现，这表明以前的锂试验使用的目标剂量和血液水平与大量副作用和脱落有关
Consistent with prior randomized controlled trials that combined an atypical antipsychotic with lithium or valproate, 6 weeks of adjunctive aripiprazole significantly reduced manic symptoms as assessed by the change in the Young Mania Rating Scale total score. However, reflective of the investigators’ diligent efforts to minimize missing data, completion rates were as high as 79% when aripiprazole was used adjunctively and 85% for the use of lithium or valproate alone. Still, the 2.6-point reduction over placebo on the Young Mania Rating Scale suggests that aripiprazole provided only modest efficacy. Although every patient received at least 2 weeks of therapeutic serum levels of lithium or valproate before entering the randomized phase, clinically useful historical information regarding the duration of lithium/valproate use was not reported. Additionally, the mean blood levels of lithium and valproate among patients who were deemed partial nonresponders were< 0.8 mmol/l and< 78 µg/ml, respectively. When faced with a partially responsive bipolar I manic patient with similar blood levels, we expect that many clinicians would increase the dose of lithium or valproate further, prior to adding a second medication. However, new perspectives on the dosing and tolerability of lithium have emerged, suggesting that previous trials of lithium used target doses and blood levels that were associated with substantial side effects and dropout