Department of Psychiatry, Copenhagen Psychiatric Centre, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
J Clin Psychiatry. 2014 Dec;75(12):1347-55. doi: 10.4088/JCP.13m08839.
Available drug treatments for bipolar disorder fail to reverse patients' cognitive deficits. Erythropoietin has neurotrophic actions and aids neurocognitive function. The aim of the study was to investigate the potential of erythropoietin to treat cognitive dysfunction in bipolar disorder.
Patients with an ICD-10 diagnosis of bipolar disorder in remission were randomized, with stratification by age and gender, to receive 8 weekly erythropoietin (40,000 IU) or saline (sodium chloride [NaCl], 0.9%) infusions in a double-blind, parallel-group design. The first patient was randomized in September 2009 and last assessment was completed in October 2012. Patients were assessed at baseline and at weeks 9 and 14. The primary outcome was change in verbal memory indexed by the total words recalled across Rey Auditory Verbal Learning Test learning trials (I-V) from baseline to week 9; secondary outcomes were sustained attention and facial expression recognition; and tertiary outcomes were attention, executive function, subjective cognitive function, and mood. Analysis was by intention to treat, using repeated-measures analysis of covariance adjusted for stratification variables and mood. The statistical threshold for which results were considered significant was P ≤ .05 (2-tailed).
44 patients were randomized; given 1 dropout after baseline, results were analyzed for 43 patients (erythropoietin: n = 23; saline: n = 20). There was no significant improvement of verbal memory in erythropoietin versus saline groups (P = .10). However, erythropoietin enhanced sustained attention (P = .001), recognition of happy faces (P = .03), and speed of complex information processing across learning, attention, and executive function (P = .01). These effects occurred in absence of changes in simple reaction times or mood (P values ≥ .16) and were maintained after red blood cell normalization.
This is the first trial investigating erythropoietin to treat cognitive dysfunction in bipolar disorder. The findings highlight erythropoietin as a candidate treatment for deficits in attention and executive function in bipolar disorder.
ClinicalTrials.gov identifier: NCT00916552.
现有的双相情感障碍药物治疗未能逆转患者的认知缺陷。促红细胞生成素具有神经营养作用，并有助于神经认知功能。本研究的目的是探讨促红细胞生成素治疗双相情感障碍认知功能障碍的潜力。
根据 ICD-10 诊断为缓解期双相情感障碍的患者，采用分层随机（按年龄和性别分层），接受每周 8 次促红细胞生成素（40000IU）或生理盐水（氯化钠[NaCl]，0.9%）输注的双盲、平行组设计。第一位患者于 2009 年 9 月随机分组，最后一次评估于 2012 年 10 月完成。患者在基线时和第 9 周及第 14 周进行评估。主要结局是通过 Rey 听觉言语学习测试学习试验（I-V）中总单词回忆量评估的言语记忆变化，从基线到第 9 周；次要结局为持续注意力和面部表情识别；三级结局为注意力、执行功能、主观认知功能和情绪。分析采用意向治疗，使用重复测量协方差分析，根据分层变量和情绪进行调整。结果被认为有统计学意义的统计阈值为 P ≤.05（双侧）。
44 例患者被随机分组；1 例患者在基线后退出，对 43 例患者（促红细胞生成素：n = 23；生理盐水：n = 20）进行了分析。促红细胞生成素组与生理盐水组的言语记忆无显著改善（P =.10）。然而，促红细胞生成素增强了持续注意力（P =.001）、识别快乐面孔（P =.03）以及学习、注意力和执行功能的复杂信息处理速度（P =.01）。这些作用发生在简单反应时间或情绪无变化的情况下（P 值≥.16），并且在红细胞正常化后仍然存在。
这是第一项研究促红细胞生成素治疗双相情感障碍认知功能障碍的试验。研究结果强调了促红细胞生成素作为治疗双相情感障碍注意力和执行功能缺陷的候选药物。
ClinicalTrials.gov 标识符：NCT00916552。
