按需治疗——急救药物还是日常方案？

文献信息

中文摘要

波动是帕金森病（PD）治疗中的主要挑战，并随着疾病进展而日益普遍。虽然口服和器械辅助治疗（DAT）改善了症状控制，但患者仍经历致残性OFF发作，尤其是清晨OFF、延迟ON和无ON现象。越来越多的证据表明，运动和非运动波动比以往认为的更为常见，并显著导致生活质量受损。波动在发病五年内影响高达50%的患者，最终几乎影响所有病程较长的患者。除了中枢药效学改变外，外周机制如吞咽困难、胃轻瘫、肠道吸收改变以及微生物组介导的左旋多巴降解，也促成了波动。尽管口服辅助药物和DAT减少了每日OFF时间，但具有临床意义的OFF期往往持续存在。这正是按需治疗提供快速症状缓解并解决传统口服药物和DAT局限性的地方。因此，更规律甚至每日使用按需治疗可能改善PD患者的生活质量。然而，按需治疗对非运动OFF期的潜在影响需要进一步研究。副作用、操作和经济考虑应予以考虑。这一专家观点得出结论：鉴于波动的高患病率和临床相关性，按需治疗可被视为标准PD管理的组成部分，而不仅仅是罕见紧急情况下的抢救选择。对于经历清晨OFF、延迟和无ON以及可预测和不可预测OFF的患者，实施可能特别有益。

英文摘要

Fluctuations represent a major therapeutic challenge in Parkinson's disease (PD) and become increasingly prevalent with disease progression. While oral and device-aided therapies (DAT) improve symptom control, patients continue to experience disabling OFF episodes, in particular early morning OFFs, delayed ON, and no-ON phenomena. Increasing evidence suggests that both motor and non-motor fluctuations are more common than previously recognized and contribute substantially to impaired quality of life. Fluctuations affect up to 50% of patients within five years of disease onset to eventually affect almost all patients with longer duration. Beside altered central pharmacodynamics, peripheral mechanisms such as dysphagia, gastroparesis, altered intestinal absorption, and microbiome-mediated levodopa degradation, contribute to fluctuations. Although oral adjunct medication and DAT reduce daily OFF-time, clinically meaningful OFF periods often persist. This is where on-demand therapies provide rapid symptom relief and address the limitations of conventional oral medication and DAT. Hence, more regular, even daily use of on-demand therapies may improve quality of life in patients with PD. However, the potential impact of on-demand therapies on non-motor OFF periods needs further investigation. Side effects, handling and economic considerations should be taken into account. This expert perspective concludes that given the high prevalence and clinical relevance of fluctuations, on-demand therapies may be considered as an integral component of standard PD management rather than solely as a rescue option in rare emergency situations. Implementation may be particularly beneficial for patients experiencing early-morning-OFFs, delayed and no-ONs but also predictable and unpredictable OFFs.