针对经选择患者组全部患者的治疗推荐
第一选择
左旋多巴/卡比多巴
:
25/100 mg,口服(速释型),每日一次,就寝前 30-60 分钟
或
罗匹尼罗
:
最初 0.25 mg,口服,每日一次,就寝前 1-3 小时,根据反应加量,最多 4 mg/日
或
普拉克索
:
最初 0.125 mg,口服,每日一次,就寝前 2-3 小时,根据反应加量,最多 0.5 mg/日
或
氯硝西泮
:
最初 0.5 mg,口服,每日三次,或 0.5 mg,每日一次,就寝前 30 分钟,根据反应加量,最多 2 mg/日
尚无大型、随机、安慰剂对照试验可评估原发性周期性肢体运动障碍的治疗。因此并没有明确证据表明在临床实践中使用药物制剂的顺序,以及哪种药物治疗对于更加严重的症状更有效。
左旋多巴/卡比多巴、[2]Garcia-Borreguero D, Ferini-Strambi L, Kohnen R, et al. European guidelines on management of restless legs syndrome: report of a joint task force by the European Federation of Neurological Societies, the European Neurological Society and the European Sleep Research Society. Eur J Neurol. 2012;19:1385-1396.http://www.ncbi.nlm.nih.gov/pubmed/22937989?tool=bestpractice.com[5]Aurora RN, Kristo DA, Bista SR, et al. The treatment of restless legs syndrome and periodic limb movement disorder in adults-an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice Guideline. Sleep. 2012;35:1039-1062.http://www.aasmnet.org/Resources/PracticeParameters/TreatmentRLS.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/22851801?tool=bestpractice.com[31]Benes H, Kurella B, Kummer J, et al. Rapid onset of action of levodopa in restless legs syndrome: a double-blind, randomized, multicenter, crossover trial. Sleep. 1999;22:1073-1081.http://www.ncbi.nlm.nih.gov/pubmed/10617168?tool=bestpractice.com[32]Collado-Seidel V, Kazenwadel J, Wetter TC, et al. A controlled study of additional sr-L-dopa in L-dopa-responsive restless legs syndrome with late-night symptoms. Neurology. 1999;52:285-290.http://www.ncbi.nlm.nih.gov/pubmed/9932945?tool=bestpractice.com[33]De Mello MT, Esteves AM, Tufik S. Comparison between dopaminergic agents and physical exercise as treatment for periodic limb movements in patients with spinal cord injury. Spinal Cord. 2004;42:218-221.http://www.nature.com/sc/journal/v42/n4/full/3101575a.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/15060518?tool=bestpractice.com罗匹尼罗、[34]Saletu M, Anderer P, Saletu B, et al. Sleep laboratory studies in periodic limb movement disorder (PLMD) patients as compared with normals and acute effects of ropinirole. Hum Psychopharmacol. 2001;16:177-187.http://www.ncbi.nlm.nih.gov/pubmed/12404588?tool=bestpractice.com减少睡眠周期性肢体运动和改善清晨性能指标:低质量的证据表明,罗匹尼罗可减少周期性肢体运动障碍患者的睡眠周期性肢体运动,并提高清晨性能指标。[34]Saletu M, Anderer P, Saletu B, et al. Sleep laboratory studies in periodic limb movement disorder (PLMD) patients as compared with normals and acute effects of ropinirole. Hum Psychopharmacol. 2001;16:177-187.http://www.ncbi.nlm.nih.gov/pubmed/12404588?tool=bestpractice.com低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。普拉克索、[37]Montplaisir J, Nicolas A, Denesle R, et al. Restless legs syndrome improved by pramipexole: a double-blind randomized trial. Neurology. 1999;52:938-943.http://www.ncbi.nlm.nih.gov/pubmed/10102409?tool=bestpractice.com减少睡眠周期性肢体运动和 PLMS-觉醒指数:中等质量证据表明,普拉克索可减少不安腿综合征患者的睡眠周期性肢体运动和 PLMS-觉醒指数。试验同时表明普拉克索可缓解睡时和夜间的腿部不适。[37]Montplaisir J, Nicolas A, Denesle R, et al. Restless legs syndrome improved by pramipexole: a double-blind randomized trial. Neurology. 1999;52:938-943.http://www.ncbi.nlm.nih.gov/pubmed/10102409?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。和阿片类药物对不安腿综合征相关的睡眠周期性肢体运动会改善症状。[5]Aurora RN, Kristo DA, Bista SR, et al. The treatment of restless legs syndrome and periodic limb movement disorder in adults-an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice Guideline. Sleep. 2012;35:1039-1062.http://www.aasmnet.org/Resources/PracticeParameters/TreatmentRLS.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/22851801?tool=bestpractice.com然而,已经开展研究评估治疗周期性肢体运动障碍的最佳阿片类药物剂量,但研究尚不充分。一项研究表明,氯硝西泮可减少原发性周期性肢体运动障碍中睡眠周期性肢体运动的发生率。[38]Ohanna N, Peled R, Rubin AH, et al. Periodic leg movements in sleep; effect of clonazepam treatment. Neurology. 1985;35:408-411.http://www.ncbi.nlm.nih.gov/pubmed/3974901?tool=bestpractice.com减少原发性周期性肢体运动障碍的睡眠周期性肢体运动的频率:低质量证据表明,氯硝西泮可减少原发性周期性肢体运动障碍中睡眠周期性肢体运动的发生率。研究表明氯硝西泮改善了睡眠周期性肢体运动患者的主观诉病并减少腿部运动的次数,且不影响运动间隔或运动持续时间。[38]Ohanna N, Peled R, Rubin AH, et al. Periodic leg movements in sleep; effect of clonazepam treatment. Neurology. 1985;35:408-411.http://www.ncbi.nlm.nih.gov/pubmed/3974901?tool=bestpractice.com低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。另一项研究表明氯硝西泮与认知行为疗法在治疗上没有差别。[39]Edinger JD, Fins AI, Sullivan RJ, et al. Comparison of cognitive-behavioral therapy and clonazepam for treating periodic limb movement disorder. Sleep. 1996;19:442-444.http://www.ncbi.nlm.nih.gov/pubmed/8843536?tool=bestpractice.com改善周期性肢体运动障碍患者的睡眠:一项小型随机研究(16 名患者)的低质量证据表明,氯硝西泮与认知行为疗法在治疗周期性肢体运动障碍的结局上没有区别。[39]Edinger JD, Fins AI, Sullivan RJ, et al. Comparison of cognitive-behavioral therapy and clonazepam for treating periodic limb movement disorder. Sleep. 1996;19:442-444.http://www.ncbi.nlm.nih.gov/pubmed/8843536?tool=bestpractice.com低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。进一步证据表明氯硝西泮显著改善客观睡眠效率和主观睡眠质量,但是没有减少每小时睡眠的 PLMS 指数。[40]Saletu M, Anderer P, Saletu-Zyhlarz G, et al. Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam. Eur Neuropsychopharmacol. 2001;11:153-161.http://www.ncbi.nlm.nih.gov/pubmed/11313161?tool=bestpractice.com改善客观睡眠效率和主观睡眠质量:一项针对 16 名周期性肢体运动障碍患者的安慰剂对照研究(低质量证据)表明,氯硝西泮显著改善了客观睡眠效率和主观睡眠质量,但却没有减少每小时睡眠的睡眠周期性肢体运动指数。[40]Saletu M, Anderer P, Saletu-Zyhlarz G, et al. Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam. Eur Neuropsychopharmacol. 2001;11:153-161.http://www.ncbi.nlm.nih.gov/pubmed/11313161?tool=bestpractice.com低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。
所有药物必须从最小起始剂量开始,在可耐受不良反应时逐渐加量。