卡利拉嗪治疗伴有混合特征的双相情感障碍躁狂症：3 项试验事后汇总分析。
Cariprazine for the treatment of bipolar mania with mixed features: A post hoc pooled analysis of 3 trials.
机构信息
Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON M5T 2S8, Canada; Brain Cognition Discovery Foundation, Toronto, Ontario, Canada.
Centers of Psychiatric Excellence, New York, New York, United States.
出版信息
J Affect Disord. 2019 Oct 1;257:600-606. doi: 10.1016/j.jad.2019.07.020. Epub 2019 Jul 5.
BACKGROUND
When bipolar I disorder (BP-I) mania is accompanied by subsyndromal depressive symptoms, a more complicated illness presentation results. To qualify for the mixed features specifier during mania, the DSM-5 requires ≥3 "non-overlapping" depressive symptoms (DS); notwithstanding, concerns of this definition's ecological validity and implications for timely diagnosis remain.
METHODS
Herein, patients were pooled from three similarly-designed pivotal trials of cariprazine compared to placebo for BP-I mania (NCT00488618/NCT01058096/NCT01058668) in post hoc analyses of mixed features using three criteria: ≥3 DS (DSM-5), ≥2 DS, and Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥10. Efficacy of cariprazine compared to placebo was assessed (Week 3) by Young Mania Rating Scale (YMRS) and MADRS scores and rates of mania response and remission.
RESULTS
In pooled patients (N = 1037), cariprazine significantly improved mean YMRS scores compared to placebo for each criterion; LSMDs were ≥3 DS = -3.79 (P = .0248), ≥2 DS = -2.91 (P = .0207), and ≥10 MADRS = -5.49 (P < .0001). More cariprazine- than placebo-treated patients met YMRS response and remission criteria, reaching significance for response in ≥2 DS (34% versus 47%; number-needed-to-treat [NNT] = 8, P = .0483) and ≥10 MADRS (31% versus 57%, NNT = 4, P < .0001) and for remission in ≥2 DS (27% versus 39%, NNT = 9, P = .0462), ≥10 MADRS (23% versus 44%, NNT = 5, P < .0001). Depressive symptoms were improved compared to placebo, reaching statistical significance in the MADRS ≥10 subgroup (LSMD = -1.59, P = .0082).
LIMITATIONS
Post hoc analysis, MADRS < 18 entry criterion may have prevented assessment of MADRS changes.
CONCLUSIONS
Cariprazine significantly reduced manic and depressive symptoms in patients with mixed features with differential efficacy across the subgroups analyzed herein.
背景
当双相情感障碍 I 型（BP-I）躁狂伴有亚综合征性抑郁症状时，会出现更复杂的疾病表现。为了在躁狂中符合混合特征的标准，DSM-5 要求至少有 3 个“不重叠”的抑郁症状（DS）；尽管如此，人们仍然对该定义的生态有效性和对及时诊断的影响表示担忧。
方法
在此，对卡利拉嗪治疗 BP-I 躁狂的三项类似设计的关键性试验（NCT00488618/NCT01058096/NCT01058668）中的患者进行了事后混合特征分析，使用三个标准来评估混合特征：≥3 个 DS（DSM-5）、≥2 个 DS 和蒙哥马利-阿斯伯格抑郁评定量表（MADRS）总分≥10。采用 Young 躁狂评定量表（YMRS）和 MADRS 评分评估卡利拉嗪与安慰剂相比的疗效（第 3 周），以及躁狂反应和缓解的比例。
结果
在汇总患者（N=1037）中，与安慰剂相比，卡利拉嗪在每个标准上均显著改善了 YMRS 评分的平均值；LS 均值分别为≥3 个 DS= -3.79（P=0.0248），≥2 个 DS= -2.91（P=0.0207），MADRS 总分≥10= -5.49（P<0.0001）。与安慰剂相比，更多的卡利拉嗪治疗患者达到了 YMRS 反应和缓解标准，在≥2 个 DS（34%对 47%；需要治疗的人数[NNT]为 8，P=0.0483）和 MADRS 总分≥10（31%对 57%，NNT 为 4，P<0.0001）方面达到了统计学意义，在≥2 个 DS（27%对 39%，NNT 为 9，P=0.0462）和 MADRS 总分≥10（23%对 44%，NNT 为 5，P<0.0001）方面达到了缓解标准。与安慰剂相比，抑郁症状得到了改善，在 MADRS 总分≥10 亚组中达到了统计学意义（LS 均值= -1.59，P=0.0082）。
局限性
事后分析，MADRS<18 的纳入标准可能阻止了 MADRS 变化的评估。
结论
卡利拉嗪显著减轻了伴有混合特征的患者的躁狂和抑郁症状，在分析的亚组中具有不同的疗效。
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