Schmidt Lejla Sjanic, Petersen Jeff Zarp, Vinberg Maj, Hageman Ida, Olsen Niels Vidiendal, Kessing Lars Vedel, Jørgensen Martin Balslev, Miskowiak Kamilla Woznica
Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Neurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Center, Psychiatric Center Copenhagen, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
Trials. 2018 Apr 19;19(1):234. doi: 10.1186/s13063-018-2627-2.
Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, but its use is impeded by its cognitive side effects. Novel treatments that can counteract these side effects may therefore improve current treatment strategies for depression. The present randomized trial investigates (1) whether short-term add-on treatment with erythropoietin (EPO) can reduce the cognitive side -effects of ECT and (2) whether such effects are long-lasting. Further, structural and functional magnetic resonance imaging (MRI) will be used to explore the neural underpinnings of such beneficial effects of EPO. Finally, the trial examines whether potential protective effects of EPO on cognition are accompanied by changes in markers of oxidative stress, inflammation, and neuroplasticity.
METHODS/DESIGN: The trial has a double-blind, randomized, placebo-controlled, parallel group design. Patients with unipolar or bipolar disorder with current moderate to severe depression referred to ECT (N = 52) are randomized to receive four high-dose infusions of EPO (40,000 IU/ml) or placebo (saline). The first EPO/saline infusion is administered within 24 h before the first ECT. The following three infusions are administered at weekly intervals immediately after ECT sessions 1, 4, and 7. Cognition assessments are conducted at baseline, after the final EPO/saline infusion (3 days after eight ECT sessions), and at a 3 months follow-up after ECT treatment completion. The neuronal substrates for potential cognitive benefits of EPO are investigated with structural and functional MRI after the final EPO/saline infusion. The primary outcome is change from baseline to after EPO treatment (3 days after eight ECT sessions) in a cognitive composite score spanning attention, psychomotor speed, and executive functions. With a sample size of N = 52 (n = 26 per group), we have ≥ 80% power to detect a clinically relevant between-group difference in the primary outcome measure at an alpha level of 5% (two-sided test). Behavioral, mood, and blood-biomarker data will be analyzed using repeated measures analysis of covariance. Functional MRI data will be preprocessed and analyzed using the FMRIB Software Library.
If EPO is found to reduce the cognitive side effects of ECT, this could have important implications for future treatment strategies for depression and for the scientific understanding of the neurobiological etiology of cognitive dysfunction in patients treated with ECT.
ClinicalTrials.gov, NCT03339596 . Registered on 10 November 2017.
电休克疗法（ECT）是治疗重度抑郁症最有效的方法，但其认知副作用阻碍了该疗法的应用。因此，能够抵消这些副作用的新型治疗方法可能会改善当前的抑郁症治疗策略。本随机试验旨在研究：（1）促红细胞生成素（EPO）短期附加治疗是否能减轻ECT的认知副作用；（2）这些效果是否具有持久性。此外，将使用结构和功能磁共振成像（MRI）来探究EPO这种有益效果的神经基础。最后，该试验将研究EPO对认知的潜在保护作用是否伴随着氧化应激、炎症和神经可塑性标志物的变化。
方法/设计：该试验采用双盲、随机、安慰剂对照、平行组设计。将转诊接受ECT治疗的52例单相或双相情感障碍伴中重度抑郁症患者随机分为两组，分别接受4次高剂量EPO（40,000 IU/ml）或安慰剂（生理盐水）输注。首次EPO/生理盐水输注在首次ECT治疗前24小时内进行。接下来的3次输注在ECT治疗第1、4和7次后每周立即进行。在基线、最后一次EPO/生理盐水输注后（8次ECT治疗后3天）以及ECT治疗完成后3个月随访时进行认知评估。在最后一次EPO/生理盐水输注后，通过结构和功能MRI研究EPO潜在认知益处的神经基质。主要结局指标是从基线到EPO治疗后（8次ECT治疗后3天）认知综合评分的变化，该评分涵盖注意力、精神运动速度和执行功能。样本量为N = 52（每组n = 26），在α水平为5%（双侧检验）时，我们有≥80%的把握度检测到主要结局指标上具有临床意义的组间差异。行为、情绪和血液生物标志物数据将使用重复测量协方差分析进行分析。功能MRI数据将使用FMRIB软件库进行预处理和分析。
如果发现EPO能减轻ECT的认知副作用，这可能对未来抑郁症治疗策略以及对ECT治疗患者认知功能障碍神经生物学病因的科学理解具有重要意义。
ClinicalTrials.gov，NCT03339596。于2017年11月10日注册。
