Miskowiak Kamilla W, Vinberg Maj, Christensen Ellen M, Bukh Jens D, Harmer Catherine J, Ehrenreich Hannelore, Kessing Lars V
Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Department of Psychiatry, University of Oxford, Oxford, UK.
Neuropsychopharmacology. 2014 May;39(6):1399-408. doi: 10.1038/npp.2013.335. Epub 2013 Dec 10.
Pharmacological treatments for depression have insufficient efficacy in 30-40% of patients and fail to reverse cognitive deficits. Erythropoietin (EPO) has neurotrophic actions and aids neurocognitive function. The aim of this exploratory study was to determine whether recombinant human EPO improves mood and memory in treatment-resistant depression. Forty treatment-resistant depressed unipolar patients with Hamilton Depression Rating Scale-17 (HDRS-17) score ≥ 17 were randomized to eight weekly EPO (Eprex; 40,000 IU) or saline infusions in a double-blind, placebo-controlled, parallel-group design. Patients were assessed at baseline and at weeks 5, 9, and 14. Primary outcome was reduction in HDRS-17 score. Global assessment of function (GAF) was reported in addition. Secondary outcome was remission rate, and tertiary outcomes were changes in Rey Auditory Verbal Learning Test (RAVLT), Beck Depression Inventory-21 (BDI-21), and World Health Organization Quality of life-BREF (WHOQOL-BREF). Exploratory outcomes were depression and cognition composite scores. HDRS-17, GAF, and remission rates showed no effects of EPO over saline at week 9 (P-value ≥ 0.09). However, EPO improved BDI (P=0.02) and WHOQOL-BREF (P=0.01), and this was maintained at follow-up week 14 (P-values ≤ 0.04). EPO enhanced verbal recall (P=0.02) and recognition (P=0.03), which was sustained at follow-up (P-values ≤ 0.04). Exploratory analysis in patients fulfilling depression severity criteria at trial start revealed ameliorated HDRS-17 in EPO (N=14) vs saline groups (N=17), which was sustained at week 14 (P-values ≤ 0.05). Exploratory analysis in the complete cohort showed that EPO reduced depression composite at weeks 9 and 14 (P-values=0.02). The findings of this exploratory study highlight EPO as an interesting compound for treatment-resistant depression, which deserves further investigation.
抑郁症的药物治疗对30%-40%的患者疗效不足，且无法逆转认知缺陷。促红细胞生成素（EPO）具有神经营养作用，有助于神经认知功能。这项探索性研究的目的是确定重组人促红细胞生成素是否能改善难治性抑郁症患者的情绪和记忆力。40名汉密尔顿抑郁量表-17（HDRS-17）评分≥17的难治性单相抑郁症患者被随机分为两组，在双盲、安慰剂对照、平行组设计中，一组接受为期8周的促红细胞生成素（益比奥；40,000国际单位）静脉输注，另一组接受生理盐水输注。在基线以及第5、9和14周对患者进行评估。主要结局指标是HDRS-17评分的降低。此外还报告了功能的整体评估（GAF）。次要结局指标是缓解率，三级结局指标是雷伊听觉词语学习测验（RAVLT）、贝克抑郁量表-21（BDI-21）和世界卫生组织生活质量简表（WHOQOL-BREF）的变化。探索性结局指标是抑郁和认知综合评分。在第9周时，HDRS-17、GAF和缓解率显示促红细胞生成素与生理盐水相比无显著效果（P值≥0.09）。然而，促红细胞生成素改善了BDI（P=0.02）和WHOQOL-BREF（P=0.01），且在第14周随访时维持该效果（P值≤0.04）。促红细胞生成素增强了言语回忆（P=0.02）和识别能力（P=0.03），且在随访时持续存在（P值≤0.04）。对试验开始时符合抑郁症严重程度标准的患者进行的探索性分析显示，促红细胞生成素组（N=14）与生理盐水组（N=17）相比，HDRS-17有所改善，且在第14周时维持该效果（P值≤0.05）。对整个队列的探索性分析表明，促红细胞生成素在第9周和第14周时降低了抑郁综合评分（P值=0.02）。这项探索性研究的结果突出了促红细胞生成素作为一种治疗难治性抑郁症的有趣化合物，值得进一步研究。
