Theal Jeremy J, Toosi Mohssen N, Girlan Larisa, Heslegrave Ronald J, Huet Pierre-Michel, Burak Kelly W, Swain Mark, Tomlinson George A, Heathcote E Jenny
Department of Medicine, University Health Network, University of Toronto, Toronto, Canada.
Hepatology. 2005 Jun;41(6):1305-12. doi: 10.1002/hep.20698.
Fatigue is common in primary biliary cirrhosis (PBC). Altered central serotonergic neurotransmission may be involved in its pathogenesis. This multicenter, randomized, double-blind, placebo-controlled, crossover trial evaluated the efficacy of ondansetron, a selective 5-HT3 receptor subtype antagonist, for treating fatigue in PBC. A crossover design was chosen, allowing subjects to serve as their own controls-appropriate to evaluate fatigue, a subjective symptom. Sixty patients with clinically stable PBC, a Fatigue Severity Score (FSS) > 4, and no other identifiable cause for fatigue were enrolled. Subjects were randomized to receive ondansetron (4 mg) or placebo orally 3 times daily for 4 weeks (period 1). Subjects then crossed over, after a minimum 1-week washout period, for a further 4 weeks of ondansetron or placebo (period 2). Fatigue was measured at the beginning and end of each period by using the FSS and Fatigue Impact Scale (FIS). Six patients withdrew; the remaining 54 subjects had a mean baseline FSS of 5.55 (+/-0.1). Response to study medication in period 1 versus period 2 was not uniform; thus, it was necessary to analyze the trial periods separately. In period 1, there was no significant additional fatigue reduction on ondansetron over placebo. During period 2, FSS and FIS decreased significantly on ondansetron versus placebo (P = .001). However, period 2 results were invalidated because drug side effects unblinded subjects (constipation affected 63.0% of patients taking ondansetron, versus 13.3% on placebo). In conclusion, ondansetron administration did not confer clinically significant fatigue reduction when compared with placebo in our study population.
疲劳在原发性胆汁性肝硬化（PBC）中很常见。中枢5-羟色胺能神经传递改变可能参与其发病机制。这项多中心、随机、双盲、安慰剂对照、交叉试验评估了选择性5-HT3受体亚型拮抗剂昂丹司琼治疗PBC疲劳的疗效。采用交叉设计，让受试者作为自身对照——这适合评估疲劳这种主观症状。招募了60例临床稳定的PBC患者，疲劳严重程度评分（FSS）>4，且无其他可识别的疲劳原因。受试者被随机分为口服昂丹司琼（4mg）或安慰剂，每日3次，共4周（第1阶段）。然后，在至少1周的洗脱期后，受试者交叉接受另外4周的昂丹司琼或安慰剂治疗（第2阶段）。在每个阶段开始和结束时，使用FSS和疲劳影响量表（FIS）测量疲劳程度。6例患者退出；其余54例受试者的平均基线FSS为5.55（±0.1）。第1阶段与第2阶段对研究药物的反应不一致；因此，有必要分别分析试验阶段。在第1阶段，与安慰剂相比，昂丹司琼没有显著额外减轻疲劳。在第2阶段，与安慰剂相比，昂丹司琼组的FSS和FIS显著降低（P = 0.001）。然而，第2阶段的结果无效，因为药物副作用使受试者未被盲法（便秘影响了63.0%服用昂丹司琼的患者，而服用安慰剂的患者为13.3%）。总之，在我们的研究人群中，与安慰剂相比，使用昂丹司琼并未带来临床上显著的疲劳减轻。
