Western Elin, Nordenmark Tonje Haug, Sorteberg Wilhelm, Sorteberg Agnes, Karic Tanja, Sorteberg Angelika
1Department of Physical Medicine and Rehabilitation, Oslo University Hospital.
2Department of Psychology, University of Oslo.
J Neurosurg. 2021 Oct 29;136(6):1705-1715. doi: 10.3171/2021.7.JNS211305. Print 2022 Jun 1.
Fatigue after aneurysmal subarachnoid hemorrhage (aSAH) is common and usually long-lasting, and it has a considerable negative impact on health-related quality of life (HRQOL), social functioning, and the ability to return to work (RTW). No effective treatment exists. The dopaminergic regulator (-)-OSU6162 has shown promising results regarding the mitigation of fatigue in various neurological diseases, and therefore the authors aimed to investigate the efficacy of (-)-OSU6162 in alleviating fatigue and other sequelae after aSAH.
A double-blind, randomized, placebo-controlled, single-center trial was performed in which 96 participants with post-aSAH fatigue were administered 30-60 mg/day of (-)-OSU6162 or placebo over a period of 12 weeks. Efficacy was assessed using the Fatigue Severity Scale (FSS), the Mental Fatigue Scale (MFS), the Beck Anxiety Inventory (BAI), the Beck Depression Inventory II (BDI-II), the SF-36 questionnaire, and a neuropsychological test battery. Assessments were performed at baseline, after 1, 4, 8, and 12 weeks of treatment, and at follow-up, 8 weeks after treatment.
The 96 participants with post-aSAH fatigue were randomized to treatment with (-)-OSU6162 (n = 49) or placebo (n = 47). The FSS, MFS, and BDI scores improved significantly in both groups after 12 weeks of treatment, whereas the BAI scores improved in the placebo group only. HRQOL improved significantly in the SF-36 domain "Vitality" in both groups. Neuropsychological test performances were within the normal range at baseline and not affected by treatment. The FSS score was distinctly improved in patients with complete RTW upon treatment with (-)-OSU6162. Concomitant use of antidepressants improved the efficacy of (-)-OSU6162 on the FSS score at week 1 beyond the placebo response, and correspondingly the use of beta- or calcium-channel blockers improved the (-)-OSU6162 efficacy beyond the placebo response in MFS scores at week 4 of treatment. There was a significant correlation between improvement in FSS, BAI, and BDI scores and the plasma concentration of (-)-OSU6162 at the dose of 60 mg/day. No serious adverse events were attributable to the treatment, but dizziness was reported more often in the (-)-OSU6162 group.
Fatigue and other sequelae after aSAH were similarly alleviated by treatment with (-)-OSU6162 and placebo. (-)-OSU6162 improved fatigue, as measured with the FSS score, significantly in patients with complete RTW. There seemed to be synergetic effects of (-)-OSU6162 and medications interfering with dopaminergic pathways that should be explored further. The strong placebo response may be exploited in developing nonpharmacological treatment programs for post-aSAH fatigue.
动脉瘤性蛛网膜下腔出血（aSAH）后的疲劳很常见且通常持续时间较长，对健康相关生活质量（HRQOL）、社会功能以及重返工作岗位（RTW）的能力有相当大的负面影响。目前尚无有效治疗方法。多巴胺能调节剂（-）-OSU6162在减轻各种神经系统疾病的疲劳方面已显示出有前景的结果，因此作者旨在研究（-）-OSU6162在减轻aSAH后疲劳及其他后遗症方面的疗效。
进行了一项双盲、随机、安慰剂对照、单中心试验，96例aSAH后疲劳的参与者在12周内每天服用30 - 60 mg的（-）-OSU6162或安慰剂。使用疲劳严重程度量表（FSS）、精神疲劳量表（MFS）、贝克焦虑量表（BAI）、贝克抑郁量表第二版（BDI-II）、SF - 36问卷和一套神经心理测试来评估疗效。在基线、治疗1、4、8和12周后以及治疗后8周的随访时进行评估。
96例aSAH后疲劳的参与者被随机分为接受（-）-OSU6162治疗组（n = 49）或安慰剂组（n = 47）。治疗12周后，两组的FSS、MFS和BDI评分均显著改善，而BAI评分仅在安慰剂组有所改善。两组在SF - 36领域“活力”方面的HRQOL均显著改善。神经心理测试表现基线时在正常范围内且不受治疗影响。接受（-）-OSU6162治疗后完全RTW的患者FSS评分明显改善。同时使用抗抑郁药在第1周时使（-）-OSU616对FSS评分的疗效超过安慰剂反应，相应地，在治疗第4周时使用β受体阻滞剂或钙通道阻滞剂使（-）-OSU6162对MFS评分的疗效超过安慰剂反应。FSS、BAI和BDI评分的改善与每天60 mg剂量的（-）-OSU6162血浆浓度之间存在显著相关性。治疗未导致严重不良事件，但（-）-OSU6162组报告头晕更频繁。
（-）-OSU6162和安慰剂治疗在减轻aSAH后的疲劳及其他后遗症方面效果相似。（-）-OSU6162在完全RTW的患者中，以FSS评分衡量，显著改善了疲劳。（-）-OSU6162与干扰多巴胺能途径的药物之间似乎存在协同作用，应进一步探索。在为aSAH后疲劳制定非药物治疗方案时，可能可以利用强烈的安慰剂反应。
