Bell Lynum Karimah S, Castro Christine F, Zhang Zhen, Patel Mehul, Tohen Mauricio
Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA.
Lundbeck LLC, Deerfield, IL, USA.
Int J Bipolar Disord. 2024 Oct 27;12(1):37. doi: 10.1186/s40345-024-00358-3.
Increased awareness of the factors contributing to the diagnostic disparities seen in bipolar disorder between individuals of different heritage is needed to achieve equity in diagnosis and treatment. One such inequity is the provision of earlier treatment. Earlier treatment of patients diagnosed with bipolar disorder may prolong time to recurrence of mood episodes and reduce functional impairment and other poor outcomes associated with disease progression. The aim of this post hoc analysis was to study the efficacy and safety of long-acting injectable aripiprazole once-monthly 400 mg (AOM 400) in patients with earlier-stage bipolar I disorder (BP-I). Data from a 52-week multicenter, double-blind, placebo-controlled, randomized withdrawal trial of AOM 400 versus placebo in patients with BP‑I (NCT01567527) were analyzed. Those patients in the lowest quartiles for age (18-≤32 years; n = 70) or disease duration (0.13-≤4.6 years; n = 67) at baseline were categorized with earlier-stage BP-I. The primary endpoint was time from randomization to recurrence of any mood episode. Other endpoints included proportion of patients with recurrence of any mood episode, and change from baseline in Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) total scores.
Maintenance treatment with AOM 400 significantly delayed time to recurrence of any mood episode versus placebo in patients aged 18-≤32 years (hazard ratio [HR]: 2.46 [95% confidence interval (CI) 1.09, 5.55]; p = 0.0251) or with disease duration 0.13-≤4.6 years (HR: 3.21 [95% CI 1.35, 7.65]; p = 0.005). This was largely driven by a lower proportion of patients in the AOM 400 group with YMRS total score ≥15 or clinical worsening. Changes from baseline in MADRS total score in both earlier-stage groups indicated AOM 400 did not worsen depression versus placebo. The safety profile of AOM 400 was consistent with the original study. Note that the original study included patients who had previously been stabilized on AOM 400 monotherapy, which may have enriched the population with patients who respond to and tolerate AOM 400.
In this post hoc analysis, AOM 400 prolonged time to recurrence of any mood episode versus placebo in earlier-stage BP-I. These findings support early initiation of maintenance treatment with AOM 400.
为了在双相情感障碍的诊断和治疗中实现公平，需要提高对不同遗传背景个体间诊断差异相关因素的认识。其中一种不公平现象是早期治疗的提供。对被诊断为双相情感障碍的患者进行早期治疗可能会延长情绪发作复发的时间，并减少与疾病进展相关的功能损害和其他不良后果。这项事后分析的目的是研究长效注射用阿立哌唑每月400毫克（AOM 400）在早期双相I型障碍（BP-I）患者中的疗效和安全性。分析了一项为期52周的多中心、双盲、安慰剂对照、随机撤药试验的数据，该试验比较了AOM 400与安慰剂在BP-I患者中的疗效（NCT01567527）。那些在基线时年龄处于最低四分位数（18至≤32岁；n = 70）或病程处于最低四分位数（0.13至≤4.6年；n = 67）的患者被归类为早期BP-I。主要终点是从随机分组到任何情绪发作复发的时间。其他终点包括任何情绪发作复发的患者比例，以及Young躁狂评定量表（YMRS）和蒙哥马利-Åsberg抑郁评定量表（MADRS）总分相对于基线的变化。
在18至≤32岁的患者中，与安慰剂相比，AOM 400维持治疗显著延迟了任何情绪发作复发的时间（风险比[HR]：2.46[95%置信区间（CI）1.09，5.55]；p = 0.0251），在病程为0.13至≤4.6年的患者中也是如此（HR：3.21[95%CI 1.35，7.65]；p = 0.005）。这主要是由于AOM 400组中YMRS总分≥15或临床恶化的患者比例较低。两个早期组中MADRS总分相对于基线的变化表明，与安慰剂相比，AOM 400没有使抑郁加重。AOM 与原始研究一致。请注意，原始研究纳入了之前已通过AOM 400单药治疗稳定病情的患者，这可能使对AOM 400有反应并能耐受的患者群体有所富集。
在这项事后分析中，与安慰剂相比，AOM 400在早期BP-I中延长了任何情绪发作复发的时间。这些发现支持早期开始使用AOM 400进行维持治疗。
