Eli Lilly and Company, Indianapolis, IN 46285, USA.
J Affect Disord. 2012 Feb;136(3):733-9. doi: 10.1016/j.jad.2011.09.051. Epub 2011 Oct 28.
Bipolar disorder represents a major public health concern and, despite treatment, is characterized by recurring episodes of mania, depression, or mixed states. Prevention of relapse or recurrence is a primary treatment objective in the management of the disorder. The objective of the current study was to identify predictors of relapse/recurrence in patients with bipolar I disorder treated with olanzapine, lithium, divalproex, or olanzapine plus divalproex/lithium.
Data from four clinical trials studying the efficacy of olanzapine compared to placebo and active comparators (lithium, divalproex, olanzapine plus divalproex/lithium) for bipolar I disorder were pooled for this analysis. Patients achieving remission after pharmacological treatment and entering randomized double-blind maintenance phase for 44 to 72 weeks were included. Cox Proportional Hazard models and Kaplan-Meier analyses were used to determine predictors of relapse/recurrence for the pooled data and within each treatment group.
A total of 929 patients meeting the criteria for remission and followed by maintenance treatment were included in this analysis, and 427 patients (46.0%) experienced symptomatic relapse/recurrence during the follow-up period. A 21-item Hamilton Depression Rating Scale (HAMD-21) total score<4, gender, rapid cycling and treatment emerged as significant predictors of relapse/recurrence and may be generalized to treatment with olanzapine and to some extent to treatment with lithium and divalproex. The results on treatment-specific predictors of relapse/recurrence are considered to be exploratory and no adjustments were made for multiple comparisons.
The major findings from this study suggest that a HAMD-21 total score<4 may be a better predictor of maintenance of remission in bipolar I patients than HAMD-21 total score<8. The prophylactic effect of olanzapine, lithium, divalproex, olanzapine plus divalproex or lithium, and placebo was assessed and baseline predictors of relapse/recurrence were identified.
双相情感障碍是一个主要的公共卫生关注点，尽管进行了治疗，但仍以反复发作的躁狂、抑郁或混合状态为特征。预防复发或复发是该疾病治疗的主要目标。本研究的目的是确定接受奥氮平、锂、丙戊酸钠或奥氮平加丙戊酸钠/锂治疗的 I 型双相情感障碍患者复发/复发的预测因素。
对四项研究奥氮平与安慰剂和活性对照（锂、丙戊酸钠、奥氮平加丙戊酸钠/锂）治疗 I 型双相情感障碍疗效的临床试验数据进行了汇总分析。纳入在药物治疗后达到缓解并进入 44-72 周随机双盲维持期的患者。使用 Cox 比例风险模型和 Kaplan-Meier 分析来确定汇总数据和每个治疗组中复发/复发的预测因素。
共有 929 名符合缓解标准并接受维持治疗的患者符合本分析标准，其中 427 名（46.0%）在随访期间出现症状性复发/复发。汉密尔顿抑郁量表（HAMD-21）总分<4、性别、快速循环和治疗是复发/复发的显著预测因素，这些预测因素可能适用于奥氮平治疗，在一定程度上也适用于锂和丙戊酸钠治疗。关于复发/复发的特定治疗预测因素的结果被认为是探索性的，没有进行多次比较的调整。
本研究的主要发现表明，HAMD-21 总分<4 可能是双相 I 型患者维持缓解的更好预测指标，优于 HAMD-21 总分<8。评估了奥氮平、锂、丙戊酸钠、奥氮平加丙戊酸钠/锂和安慰剂的预防作用，并确定了复发/复发的基线预测因素。
