Long-term Safety, Dose Stability, and Efficacy of Opioids for Patients With Restless Legs Syndrome in the National RLS Opioid Registry
Long-term Safety, Dose Stability, and Efficacy of Opioids for Patients With Restless Legs Syndrome in the National RLS Opioid Registry
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DOI：
10.1212/wnl.0000000000206855
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发表时间：
2023-04-04
期刊：
影响因子：
9.9
通讯作者：
Zackon, Jordana
中科院分区：
文献类型：
--
作者：
Winkelman, John Weyl;Wipper, Benjamin;Zackon, Jordana
背景与目的
不宁腿综合征（RLS）是一种感觉运动性神经系统疾病。对于难治性或症状加重的不宁腿综合征患者，会开具低剂量的阿片类药物。这些药物用于治疗不宁腿综合征的长期安全性、剂量稳定性和疗效仍不明确。在本研究中，我们报告了社区中使用阿片类药物治疗不宁腿综合征的患者样本的2年纵向数据。
方法
全国不宁腿综合征阿片类药物登记处是一项观察性纵向研究，研究对象是因确诊的不宁腿综合征而服用处方阿片类药物的个体，其中大多数人因多巴胺激动剂出现症状加重。在登记处初次登记时以及之后每6个月通过REDCap调查问卷收集有关阿片类药物剂量、副作用、过去和当前同时使用的不宁腿综合征治疗方法、不宁腿综合征严重程度、精神症状以及阿片类药物滥用风险因素等信息。研究人员未向当地医生提供反馈或干预。
结果
有2年纵向数据的登记处参与者（n = 448）大多为白人、女性、年龄超过60岁，在登记处登记时，使用阿片类药物的中位时间为1 - 3年，平均吗啡毫克当量（MME）为38.4（标准差 = 43.5）。在2年的随访期间，整个队列的不宁腿综合征严重程度没有变化。从基线到2年，每日阿片类药物剂量的中位变化为0 MME（四分位间距 = 0 - 10）。虽然41.1%的参与者在随访期间增加了剂量（中位增加量 = 10 MME），但58.9%的参与者减少了剂量或剂量无变化。只有8%和4%的参与者分别增加了>25 MME和>50 MME。那些阿片类药物剂量增加>25或>50 MME的人中，95%具有以下特征之一：更换阿片类药物、停用非阿片类不宁腿综合征治疗药物、基线时至少有轻度失眠、有抑郁症病史、男性、年龄小于45岁以及因合并疼痛使用阿片类药物。
讨论
在大多数参与者中，低剂量阿片类药物在2年的随访期间继续能充分控制难治性不宁腿综合征的症状。少数患者确实出现了较大的剂量增加，这总是与有限的一些因素相关，最显著的是阿片类和非阿片类不宁腿综合征药物的变化以及因非不宁腿综合征疾病使用阿片类药物。持续的纵向观察将有助于深入了解阿片类药物治疗严重、症状加重的不宁腿综合征的长期安全性和疗效。
证据分级
本研究提供了IV级证据，即在2年期间，当为成年难治性不宁腿综合征患者开具阿片类药物时，大约40%的患者阿片类药物剂量增加，大多数增加量较小。
Background and ObjectivesRestless legs syndrome (RLS) is a sensory-motor neurologic disorder. Low-dose opioids are prescribed for patients with refractory or augmented RLS. The long-term safety, dose stability, and efficacy of these medications for RLS treatment is still unclear. In this study, we report the 2-year longitudinal data in a sample of patients treated with opioids for RLS in the community.MethodsThe National RLS Opioid Registry is an observational longitudinal study consisting of individuals taking a prescribed opioid for diagnosed and confirmed RLS, most of whom experienced augmented symptoms from dopamine agonists. Information on opioid dosages, side effects, past and current concomitant RLS treatments, RLS severity, psychiatric symptoms, and opioid abuse risk factors was collected at initial Registry entry and every 6 months thereafter by surveys on REDCap. No feedback or intervention was provided by the study staff to local providers.ResultsRegistry participants (n = 448) with 2-year longitudinal data available were mostly White, female, older than 60 years, and, at Registry entry, had been on opioids for a median of 1-3 years at a mean morphine milligram equivalent (MME) of 38.4 (SD = 43.5). No change in RLS severity in the overall cohort was observed over the 2-year follow-up period. The median change in daily opioid dose from baseline to 2 years was 0 MME (interquartile range = 0-10). While 41.1% of participants increased their dose during the follow-up period (median increase = 10 MME), 58.9% decreased their dose or saw no change. Only 8% and 4% saw increases of >25 MME and >50 MME, respectively. Ninety-five percent of those who increased opioid dose >25 or >50 MME had one of the following features: switching opioids, discontinuation of nonopioid RLS treatment medications, at least mild insomnia at baseline, a history of depression, male sex, younger than 45 years, and opioid use for comorbid pain.DiscussionLow-dose opioid medications continue to adequately control symptoms of refractory RLS over 2 years of follow-up in most of the participants. A minority of patients did see larger dose increases, which were invariably associated with a limited number of factors, most notably changes in opioid and nonopioid RLS medications and opioid use for a non-RLS condition. Continued longitudinal observations will provide insight into the long-term safety and efficacy of opioid treatment of severe, augmented RLS.Classification of EvidenceThis study provides Class IV evidence that opioid doses increase in roughly 40% of patients, in most by small amounts, over a 2-year period when prescribed for adult refractory restless leg syndrome.