Welten Carlijn C M, Koeter Maarten W J, Wohlfarth Tamar D, Storosum Jitschak G, van den Brink Wim, Gispen-de Wied Christine C, Leufkens Hubert G M, Denys Damiaan A J P
Department of Psychiatry, Academic Medical Centre, Room PA 2-179, Meibergdreef 9, 1105AZ, Amsterdam, the Netherlands.
Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
J Clin Psychiatry. 2016 Sep;77(9):e1117-e1123. doi: 10.4088/JCP.15r10051.
To investigate whether early nonresponse to antipsychotic treatment of acute mania predicts treatment failure and, if so, to establish the best definition or criterion of an early nonresponse.
Short-term efficacy studies assessing antipsychotics that were submitted to the Dutch Medicines Evaluation Board during an 11-year period as part of the marketing authorization application for the indication of acute manic episode of bipolar disorder. Pharmaceutical companies provided their raw patient data, which enabled us to perform an individual patient data meta-analysis.
All double-blind, randomized, placebo-controlled trials assessing the efficacy of antipsychotics for acute manic episode of bipolar disorder were included (10 trials).
All patients with data available for completer analysis (N = 1,243), symptom severity scores on the Young Mania Rating Scale (YMRS) at weeks 0, 1, and 2 and at study end point (week 3 or 4).
The a priori chances of nonresponse and nonremission at study end point were 40.9% (95% CI, 38.2%-43.6%) and 65.3% (95% CI, 62.0%-68.6%), respectively. Early nonresponse in weeks 1 and 2, defined by cutoff scores ranging from a ≤ 10% to a ≤ 50% reduction in symptoms compared to baseline on the YMRS, significantly predicted nonresponse (≤ 0% symptom reduction) and nonremission (YMRS score higher than 8) in week 3. The predictive value of early nonresponse (PVnr_se) at week 1 for both nonresponse and nonremission at study end point declined linearly with increasing cutoff scores of early nonresponse; nonresponse: 76.0% (95% CI, 69.7%-82.3%) for a ≤ 10% response to 48.7% (95% CI, 45.5%-51.9%) for a ≤ 50% response; nonremission: 92.2% (95% CI, 88.3%-96.1%) for a ≤ 10% response to 76.8% (95% CI, 74.4%-79.5%) for a ≤ 50% response. A similar linear decline was observed for increasing cutoff scores of early nonresponse at week 2 for nonresponse, but not for nonremission at end point: nonresponse 90.3% (95% CI, 84.6%-96.0%) for a ≤ 10% response to 65.0% (95% CI, 61.4%-68.6%) for a ≤ 50% response; nonremission: 94.2% (95% CI, 89.7%-98.7%) for a ≤ 10% response and 93.2% (95% CI, 93.1%-95.1%) for a ≤ 50% response. Specific antipsychotic characteristics did not modify these findings at either time point (week 1: P = .127; week 2: P = .213).
When patients fail to respond early (1-2 weeks) after the initiation of antipsychotic treatment for acute mania, clinicians should reconsider their treatment choice using a 2-stage strategy.
探讨急性躁狂症患者在抗精神病药物治疗初期无反应是否预示治疗失败，若如此，则确定早期无反应的最佳定义或标准。
在11年期间提交给荷兰药品评估委员会的评估抗精神病药物的短期疗效研究，作为双相情感障碍急性躁狂发作适应症上市许可申请的一部分。制药公司提供了原始患者数据，这使我们能够进行个体患者数据荟萃分析。
纳入所有评估抗精神病药物治疗双相情感障碍急性躁狂发作疗效的双盲、随机、安慰剂对照试验（共10项试验）。
所有可获得完整分析数据的患者（N = 1243），在第0、1、2周以及研究终点（第3或4周）时的杨氏躁狂量表（YMRS）症状严重程度评分。
研究终点时无反应和未缓解的先验概率分别为40.9%（95%CI，38.2%-43.6%）和65.3%（95%CI，62.0%-68.6%）。第1周和第2周的早期无反应，根据YMRS与基线相比症状减轻幅度从≤10%到≤50%的截断分数来定义，显著预测了第3周的无反应（症状减轻≤0%）和未缓解（YMRS评分高于8）。第1周早期无反应（PVnr_se）对研究终点时无反应和未缓解的预测价值随着早期无反应截断分数的增加呈线性下降；无反应：对于≤10%的反应为76.0%（95%CI, 69.7%-82.3%），对于≤50%的反应为48.7%（95%CI, 45.5%-51.9%）；未缓解：对于≤10%的反应为92.2%（95%CI, 88.3%-96.1%），对于≤50%的反应为76.8%（95%CI, 74.4%-79.5%）。第2周早期无反应截断分数增加时，对于无反应观察到类似的线性下降，但对于终点时的未缓解则未观察到：对于≤10%的反应，无反应为90.3%（95%CI, 84.6%-96.0%），对于≤50%的反应为65.0%（95%CI, 61.4%-68.6%）；未缓解：对于≤10%的反应为94.2%（95%CI, 89.7%-98.7%），对于≤50%的反应为93.2%（95%CI, 93.1%-95.1%）。在两个时间点（第1周：P = 0.127；第2周：P = 0.213）特定抗精神病药物特征均未改变这些结果。
当急性躁狂症患者在开始抗精神病药物治疗后的早期（1 - 2周）无反应时，临床医生应采用两阶段策略重新考虑治疗选择。
