Department of Psychiatry and Psychology, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.
Department of Psychiatry and Pharmacology, University of Toronto, Toronto, ON, Canada.
J Affect Disord. 2024 Dec 1;366:136-145. doi: 10.1016/j.jad.2024.08.119. Epub 2024 Aug 24.
Patients with bipolar I disorder may experience mood destabilization or treatment-emergent affective switch (TEAS) from one symptom pole to the other spontaneously or following treatment. Optimal treatment should address symptoms from both poles without precipitating destabilization.
These were pooled post hoc analyses of data from randomized, double-blind, placebo-controlled studies of cariprazine 3-12 mg/d for bipolar I mania (NCT00488618, NCT01058096, NCT01058668) and cariprazine 1.5 mg/d or 3 mg/d for bipolar I depression (NCT01396447, NCT02670538, NCT02670551). Changes from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 6 and Young Mania Rating Scale (YMRS) total score at week 3 were analyzed in each indication using a mixed-effects model for repeated measures. Percentages of patients with increasing levels of endpoint response and TEAS (bipolar mania = MADRS total score ≥ 19; bipolar depression = YMRS score ≥ 16) were determined.
Cariprazine significantly reduced manic and depressive symptoms in patients with bipolar I disorder mood episodes. In patients with a manic episode and up to mild baseline depressive symptoms, cariprazine also significantly reduced depressive symptoms. In patients with a depressive episode and manic symptoms in remission at baseline, numerical reduction (without statistical significance) in YMRS indicated no worsening of mania. In both indications, cariprazine-treated patients had numerically greater response rates (presenting symptom pole) than placebo-treated patients; lower percentages of cariprazine- than placebo-treated patients had TEAS at visits where data were collected.
Post hoc analysis.
Results suggested that cariprazine had full-spectrum efficacy across symptoms from both poles in patients with bipolar I disorder mood episodes; TEAS risk was low. Patient-level response suggested that improvement was clinically relevant.
双相 I 型障碍患者可能会自发或在治疗后出现从一个症状极点到另一个症状极点的情绪不稳定或治疗诱发的情感转换（TEAS）。最佳治疗应针对两个极点的症状，而不会引发不稳定。
这是卡利拉嗪治疗双相 I 型躁狂症（NCT00488618、NCT01058096、NCT01058668）和卡利拉嗪治疗双相 I 型抑郁症（NCT01396447、NCT02670538、NCT02670551）的随机、双盲、安慰剂对照研究的事后分析数据的汇总。使用混合效应重复测量模型，在每个适应症中分析第 6 周时蒙特利尔抑郁评定量表（MADRS）总分和第 3 周时杨氏躁狂评定量表（YMRS）总分的变化。确定终点反应和 TEAS（双相躁狂症=MADRS 总分≥19；双相抑郁症=YMRS 评分≥16）水平升高的患者比例。
卡利拉嗪显著减轻了双相 I 型障碍发作患者的躁狂和抑郁症状。在有躁狂发作且基线时仅有轻度抑郁症状的患者中，卡利拉嗪也显著减轻了抑郁症状。在基线时有抑郁发作且躁狂症状缓解的患者中，YMRS 的数值降低（无统计学意义）表明躁狂无恶化。在这两种适应症中，卡利拉嗪治疗的患者的反应率（出现的症状极点）均高于安慰剂治疗的患者；在收集数据的就诊中，卡利拉嗪治疗的患者比安慰剂治疗的患者出现 TEAS 的比例较低。
事后分析。
结果表明，卡利拉嗪在双相 I 型障碍发作患者的两个极点的症状中具有全面的疗效；TEAS 的风险较低。患者水平的反应表明改善具有临床意义。
