Takahashi Masayoshi, Nishida Shingo, Nakamura Masaki, Kobayashi Mina, Matsui Kentaro, Ito Eiki, Usui Akira, Inoue Yuichi
Department of Somnology, Tokyo Medical University, Tokyo, Japan.
Japan Somnology Center, Neuropsychiatric Research Institute, Tokyo, Japan.
PLoS One. 2017 Mar 6;12(3):e0173535. doi: 10.1371/journal.pone.0173535. eCollection 2017.
To investigate the rate of and risk factors for restless legs syndrome (RLS) augmentation in Japanese patients receiving pramipexole (PPX) treatment. Records of 231 consecutive patients with idiopathic RLS who received PPX therapy for more than one month in a single sleep disorder center were analyzed retrospectively. Augmentation was diagnosed based on the Max Planck Institute criteria; associated factors were identified by logistic regression analysis. Mean age at PPX initiation was 60.6 ± 14.9 years and mean treatment duration was 48.5 ± 26.4 months. Augmentation was diagnosed in 21 patients (9.1%). Daily PPX dose and treatment duration were significantly associated with augmentation. By analyzing the receiver operating characteristic curve, a PPX dose of 0.375 mg/day was found to be the optimal cut-off value for predicting augmentation. After stratifying patients according to PPX treatment duration, at median treatment duration of 46 months, optimal cut-off values for daily doses were 0.375 and 0.500 mg/day for <46 months and ≥46 months of treatment, respectively. The RLS augmentation with PPX treatment in Japanese patients was occurred at rate of 9.1%, being quite compatible with previously reported rates in Caucasian patients. The symptom could appear within a relatively short period after starting the treatment in possibly vulnerable cases even with a smaller drug dose. Our results support the importance of keeping doses of PPX low throughout the RLS treatment course to prevent augmentation.
为调查日本接受普拉克索（PPX）治疗的患者中不安腿综合征（RLS）症状加重的发生率及危险因素。对在单一睡眠障碍中心接受PPX治疗超过1个月的231例连续性特发性RLS患者的记录进行回顾性分析。依据马克斯·普朗克研究所标准诊断症状加重情况；通过逻辑回归分析确定相关因素。开始使用PPX时的平均年龄为60.6±14.9岁，平均治疗时长为48.5±26.4个月。21例患者（9.1%）被诊断为症状加重。每日PPX剂量和治疗时长与症状加重显著相关。通过分析受试者工作特征曲线，发现每日0.375 mg的PPX剂量是预测症状加重的最佳临界值。根据PPX治疗时长对患者进行分层后，在治疗时长中位数为46个月时，治疗时长<46个月和≥46个月的患者每日剂量的最佳临界值分别为0.375和0.500 mg/天。日本患者接受PPX治疗时RLS症状加重的发生率为9.1%，与先前报道的白种人患者发生率相当。即使药物剂量较小，在可能易出现症状的病例中，症状可能在开始治疗后的相对短时间内出现。我们的结果支持在整个RLS治疗过程中保持低剂量PPX以预防症状加重的重要性。
