Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.
Curr Med Res Opin. 2010 Jun;26(6):1485-96. doi: 10.1185/03007991003779380.
This study evaluated the long-term tolerability and effectiveness of aripiprazole adjunctive to lithium or valproate in partial responders with bipolar mania.
Completers of a 6-week double-blind comparison of adjunctive aripiprazole versus placebo in bipolar mania partially responsive to lithium or valproate monotherapy could enter a 46-week extension treatment with open-label adjunctive aripiprazole plus lithium (ARI + LI) or valproate (ARI + VAL). Safety, efficacy and functioning were assessed.
CN138-134LT: Study of Aripiprazole in Patients With Bipolar I Disorder; ID number: NCT00257972; registry: www.clinicaltrials.gov.
In total, 283 (ARI + LI n = 108; ARI + VAL n = 175) patients entered and 146 (ARI + LI n = 55; ARI + VAL n = 91) completed the 46-week, open-label extension. Frequently reported adverse events (AEs) that occurred with ARI + LI vs. ARI + VAL were: tremor (17.0% vs. 12.1%), akathisia (6.6% vs. 8.6%), headache (6.6% vs. 4.0%), insomnia (9.4% vs. 10.3%), depression (7.5% vs. 9.2%) and weight increase (11.3% vs. 8.6%). Extrapyramidal symptom-related AEs occurred in 24 (22.6%) ARI + LI- and 38 (21.8%) ARI + VAL-treated patients, with eight discontinuations. The majority of new-onset events of akathisia and insomnia occurred early. Mean (SE) weight change from double-blind endpoint to Week 46 (LOCF) was 2.3 (0.6) kg with ARI + LI and 2.0 (0.4) kg with ARI + VAL. Significant improvements from baseline over the 52 weeks (LOCF) occurred with ARI + LI and ARI + VAL on mean (95%CI) YMRS total score (-16.5 [-18.1; -14.8] and -17.6 [-18.9; -16.3], both p < 0.001 vs. baseline) and MADRS total score (-1.7 [-3.3; -0.1], p < 0.05 vs. baseline vs. -2.7 [-4.0; -1.4], p < 0.001 vs. baseline). Over the 46-week extension, continued aripiprazole provided continued YMRS improvement with ARI + LI (-2.9) and ARI + VAL (-3.3), while mean MADRS total changes were +1.1 and +1.0, respectively, and LIFE-RIFT changes were 0.2 and -0.5, respectively.
Long-term aripiprazole adjunctive to lithium/valproate in bipolar mania was safe and well tolerated. Improvements in manic symptoms and functioning were maintained. Aripiprazole, adjunctive to either lithium or valproate, appeared to be equally safe and effective combinations for the treatment of bipolar disorder.
As an open-label extension study with a low completion rate, a conservative interpretation of the findings is warranted. Additionally, the study population was not randomly selected but chosen at the discretion of the investigator, and patients did not maintain therapeutic levels of their mood stabiliser consistently.
本研究评估了阿立哌唑作为锂或丙戊酸盐的辅助治疗在双相躁狂部分缓解患者中的长期耐受性和有效性。
在锂或丙戊酸盐单药治疗部分缓解的双相躁狂患者中，完成了为期 6 周的阿立哌唑辅助治疗与安慰剂双盲比较的患者，可以进入为期 46 周的开放标签阿立哌唑辅助治疗锂（ARI + LI）或丙戊酸盐（ARI + VAL）的扩展治疗。评估安全性、疗效和功能。
CN138-134LT：阿立哌唑治疗 I 型双相障碍患者的研究；编号：NCT00257972；注册处：www.clinicaltrials.gov。
共有 283 名（ARI + LI n = 108；ARI + VAL n = 175）患者入组，146 名（ARI + LI n = 55；ARI + VAL n = 91）患者完成了 46 周的开放标签扩展。与 ARI + LI 相比，ARI + VAL 更常报告的不良事件（AE）是：震颤（17.0% vs. 12.1%）、静坐不能（6.6% vs. 8.6%）、头痛（6.6% vs. 4.0%）、失眠（9.4% vs. 10.3%）、抑郁（7.5% vs. 9.2%）和体重增加（11.3% vs. 8.6%）。与 ARI + LI 治疗的 24 名（22.6%）患者和 ARI + VAL 治疗的 38 名（21.8%）患者相比，发生了与锥体外系症状相关的 AE，其中 8 名患者停药。大多数新发的静坐不能和失眠事件发生较早。从双盲终点到第 46 周（LOCF）的平均（SE）体重变化为 ARI + LI 组为 2.3（0.6）kg，ARI + VAL 组为 2.0（0.4）kg。在第 52 周（LOCF），与基线相比，ARI + LI 和 ARI + VAL 均显著改善了 YMRS 总分（-16.5 [-18.1；-14.8]和-17.6 [-18.9；-16.3]，均 p < 0.001）和 MADRS 总分（-1.7 [-3.3；-0.1]，p < 0.05 与基线相比；-2.7 [-4.0；-1.4]，p < 0.001 与基线相比）。在 46 周的扩展期内，阿立哌唑继续治疗可改善 YMRS 评分（ARI + LI -2.9 和 ARI + VAL -3.3），而 MADRS 总分的平均变化分别为+1.1 和+1.0，LIFE-RIFT 变化分别为 0.2 和-0.5。
阿立哌唑作为锂/丙戊酸盐的辅助治疗在双相躁狂症中是安全且耐受良好的。躁狂症状和功能的改善得以维持。阿立哌唑作为锂或丙戊酸盐的辅助治疗，对双相情感障碍的治疗似乎是同样安全和有效的组合。
由于这是一项开放标签扩展研究，且完成率较低，因此需要对研究结果进行保守解释。此外，研究人群不是随机选择的，而是由研究者自行选择的，并且患者并没有始终保持其心境稳定剂的治疗水平。
