Placebo-Controlled Adjunctive Trial of Pramipexole in Patients With Bipolar Disorder: Targeting Cognitive Dysfunction
Placebo-Controlled Adjunctive Trial of Pramipexole in Patients With Bipolar Disorder: Targeting Cognitive Dysfunction
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DOI：
10.4088/jcp.11m07299
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发表时间：
2012-01-01
影响因子：
5.3
通讯作者：
Malhotra, Anil K.
中科院分区：
文献类型：
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作者：
Burdick, Katherine E.;Braga, Raphael J.;Malhotra, Anil K.
目的：双相情感障碍患者患有严重的认知障碍，直接导致功能障碍，但很少有研究针对这些症状进行治疗，并且最佳的研究设计仍不清楚。我们评估了多巴胺 D-2/D-3 受体激动剂普拉克索对双相情感障碍认知的影响。方法：2006 年 7 月至 2010 年 4 月期间，50 名患有 DSM-IV 诊断的 I 型双相情感障碍或 II 型双相情感障碍的稳定门诊患者参加了一项为期 8 周、双盲、随机、安慰剂对照的认知增强试验。患者于 2010 年 4 月完成了神经认知测试。 基线和第 8 周，主要结果指标是为 11 项任务中每一项计算的变化分数。每周监测症状和副作用。结果：45 名患者完成了研究（安慰剂，n = 24；普拉克索，n = 21），各组在人口统计学和临床特征上匹配良好。初步认知分析表明，与安慰剂相比，普拉克索没有令人信服的认知益处；然而，二次分析强调了未来试验的几个重要的方法学问题，并确定了可能更容易从认知增强策略中受益的患者亚组。这一结果表明，研究设计在结果中发挥了非常重要的作用，意味着试验失败而不是完全负面。具体来说，我们发现，即使是基线时非常微妙的亚综合征情绪症状，也会对活性药物的改善程度产生显着影响，严格情绪正常的患者表现最好（多变量方差分析，情绪正常亚组中 P = 0.03）。此外，基线认知障碍的程度也影响治疗反应的可能性。最后，合并用药可能会减弱或在某些情况下增强对认知治疗的反应，应在研究设计中予以考虑。结论：尽管我们的结果表明普拉克索对双相情感障碍患者的认知缺乏明确的影响，但我们的数据揭示了普拉克索在亚组中的潜在有益作用，为未来开展这一研究方向提供了一些热情。此外，这项研究强调了双相情感障碍认知试验严格受试者选择的重要性。未来的研究将有必要确定这些结果可能的临床和功能影响。
Objective: Patients with bipolar disorder suffer from significant cognitive impairment that contributes directly to functional disability, yet few studies have targeted these symptoms for treatment, and the optimal study design remains unclear. We evaluated the effects of the dopamine D-2/D-3 receptor agonist pramipexole on cognition in bipolar disorder.Method: Fifty stable outpatients with DSM-IV-diagnosed bipolar I or bipolar II disorder enrolled in an 8-week, double-blind, randomized, placebo-controlled cognitive enhancement trial between July 2006 and April 2010. Patients completed neurocognitive testing at baseline and at week 8, and the primary outcome measures were change scores calculated for each of the 11 tasks. Symptoms and side effects were monitored weekly.Results: Forty-five patients completed the study (placebo, n = 24; pramipexole, n = 21), and groups were well matched on demographic and clinical features. Primary cognitive analyses indicated no compelling cognitive benefit of pramipexole versus placebo; however, secondary analyses highlight several important methodological issues for future trials and identify a subgroup of patients who might benefit more readily from cognitive enhancement strategies. This outcome suggests that the study design played a very important role in the results implying a failed rather than altogether negative trial. Specifically, we found that even very subtle, subsyndromal mood symptoms at baseline had a significant influence on the degree of improvement due to active drug, with strictly euthymic patients faring best (multivariate analysis of variance, P = .03 in euthymic subgroup). In addition, the extent of baseline cognitive impairment also contributed to the likelihood of treatment response. Finally, concomitant medications may weaken, or in some cases enhance, response to cognitive treatment and should be accounted for in study design.Conclusions: Although our results point toward a lack of clear effect of pramipexole on cognition in bipolar patients, our data revealed a potentially beneficial effect of pramipexole in a subgroup, providing some enthusiasm for pursuing this line of research in the future. Moreover, this study emphasizes the importance of rigorous subject selection for cognitive trials in bipolar illness. Future studies will be necessary to determine the possible clinical and functional implications of these results.