安慰剂对照试验未发现奥氮平与双相躁狂发作加剧之间存在关联。

Baker Robert W, Milton Denái R, Stauffer Virginia L, Gelenberg Alan, Tohen Mauricio

Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 4133, Indianapolis, IN 46285, USA.

J Affect Disord. 2003 Jan;73(1-2):147-53. doi: 10.1016/s0165-0327(02)00335-x.

BACKGROUND

Published case reports describe apparent induction or exacerbation of manic-like symptoms during treatment with the atypical antipsychotics olanzapine and risperidone. To date, such reports are from uncontrolled clinical experience and therefore cannot clarify whether the atypical antipsychotics caused such manic-like states or simply failed to prevent them. Presumably, bipolar patients would be at increased risk for this putative adverse event. Therefore, we evaluated the potential of olanzapine to exacerbate symptoms of mania compared to placebo during treatment of bipolar mania.

METHODS

Two inpatient, double-blind, randomized trials investigating the efficacy of olanzapine 5-20 mg daily versus placebo for the treatment of acute mania were combined. Two hundred and fifty-four subjects participated (placebo n=129; olanzapine n=125) in the two studies. Severity of mania was quantified with the 11-item Young-Mania Rating Scale (Y-MRS). In a post-hoc analysis, after double-blind therapy up to 3 weeks, categorical comparison of olanzapine and placebo groups was made for any worsening and worsening by 10 or 20% from baseline Y-MRS scores (LOCF).

RESULTS

The percentage of subjects with exacerbation at endpoint were: any worsening, placebo 37.7%, olanzapine 21.8% (P=0.005); >or=10% worsening, placebo 24.6%, olanzapine 14.5% (P=0.039); >or=20% worsening, placebo 15.6%, olanzapine 8.1% (P=0.064).

CONCLUSION

Mania rating scores worsened for some patients during olanzapine therapy. However, this was significantly less common with olanzapine than with placebo. These controlled data suggest that clinical case reports of occurrence of 'mania' during treatment with olanzapine, and possibly those with other atypical antipsychotics, reflect exacerbation in the natural history of bipolar illness, rather than an adverse pharmacological effect.

LIMITATIONS

Post-hoc analysis of pooled data from two different studies.

背景

已发表的病例报告描述了在使用非典型抗精神病药物奥氮平和利培酮治疗期间出现类似躁狂症状的明显诱导或加重情况。迄今为止，此类报告来自非对照临床经验，因此无法阐明非典型抗精神病药物是否导致了此类类似躁狂状态，还是仅仅未能预防它们。据推测，双相情感障碍患者出现这种假定不良事件的风险会增加。因此，我们评估了在双相躁狂症治疗期间，与安慰剂相比，奥氮平加重躁狂症状的可能性。

方法

两项针对奥氮平每日5 - 20毫克与安慰剂治疗急性躁狂症疗效的住院患者双盲随机试验进行了合并。两项研究共有254名受试者参与（安慰剂组n = 129；奥氮平组n = 125）。使用11项杨氏躁狂评定量表（Y - MRS）对躁狂严重程度进行量化。在事后分析中，双盲治疗长达3周后，对奥氮平组和安慰剂组从基线Y - MRS评分（末次观察结转）恶化10%或20%以及任何恶化情况进行分类比较。