Wood Lindy D, Neumiller Joshua J, Setter Stephen M, Dobbins Erin K
Elder Services, Spokane, Washington, USA.
Am J Geriatr Pharmacother. 2010 Aug;8(4):294-315. doi: 10.1016/j.amjopharm.2010.08.002.
Parkinson's disease (PD) is associated with a host of nonmotor symptoms, including psychosis, cognitive impairment, depression, sleep disturbance, swallowing disorders, gastrointestinal symptoms, and autonomic dysfunction. The nonmotor symptoms of PD have the potential to be more debilitating than the motor features of the disorder.
The aim of this article was to review treatment options for the nonmotor manifestations of PD, including pharmacologic and nonpharmacologic interventions.
The PubMed and MEDLINE databases were searched for articles published in English between January 1966 and April 2010, using the terms Parkinson's disease, nonmotor, psychosis, hallucination, antipsychotic, cognitive impairment, dementia, depression, sleep disturbance, sleepiness, REM (rapid eye movement) sleep behavior disorder, dysphagia, swallowing disorder, sialorrhea, gastrointestinal, constipation, autonomic dysfunction, orthostatic hypotension, gastroparesis, erectile dysfunction, sexual dysfunction, and urinary dysfunction. Articles were selected for review if they were randomized controlled trials (RCTs), meta-analyses, or evidence-based reviews of treatment of patients with PD, and/or expert opinion regarding the treatment of nonmotor symptoms of PD.
A total of 148 articles, including RCTs, meta-analyses, and evidence-based reviews, were included in this review. The treatment of hallucinations or psychosis in PD should include a stepwise reduction in medications for motor symptoms, followed by the use of quetiapine or clozapine. Dementia may be treated with acetylcholinesterase inhibitors. Evidence is lacking concerning the optimal pharmacologic treatment for depression in PD, with expert opinions indicating selective serotonin reuptake inhibitors as the antidepressants of choice. However, the largest study to date found nortriptyline therapy to be efficacious compared with placebo, whereas paroxetine controlled release was not. A variety of sleep disturbances may plague a person with PD, and treatment must be individualized to the patient's specific sleep disturbance pattern and contributing factors. Swallowing disorders may lead to aspiration and pneumonia, and patients with dysphagia should be referred to a speech therapist for further evaluation and treatment. Orthostasis may be treated with nonpharmacologic interventions as well as pharmacologic treatments (eg, fludrocortisone, midodrine, indomethacin). Other autonomic symptoms are managed in a manner similar to that in patients without PD, although careful attention must be aimed at avoiding dopamine-blocking therapies in the treatment of gastrointestinal dysfunction and gastroparesis.
Various pharmacologic and nonpharmacologic strategies are available for the management of the nonmotor symptoms of PD. The challenges associated with nonmotor symptoms must not be forgotten in light of the motor symptoms of PD, and treatment of nonmotor symptoms should be encouraged.
帕金森病(PD)与一系列非运动症状相关,包括精神病、认知障碍、抑郁、睡眠障碍、吞咽障碍、胃肠道症状和自主神经功能障碍。PD的非运动症状可能比该疾病的运动特征更使人衰弱。
本文旨在综述PD非运动表现的治疗选择,包括药物和非药物干预措施。
检索PubMed和MEDLINE数据库,查找1966年1月至2010年4月期间以英文发表的文章,使用的检索词为帕金森病、非运动、精神病、幻觉、抗精神病药、认知障碍、痴呆、抑郁、睡眠障碍、嗜睡、快速眼动(REM)睡眠行为障碍、吞咽困难、吞咽障碍、流涎、胃肠道、便秘、自主神经功能障碍、体位性低血压、胃轻瘫、勃起功能障碍、性功能障碍和排尿功能障碍。如果文章是随机对照试验(RCT)、荟萃分析或关于PD患者治疗的循证综述,和/或关于PD非运动症状治疗的专家意见,则选择纳入综述。
本综述共纳入148篇文章,包括RCT、荟萃分析和循证综述。PD患者幻觉或精神病的治疗应包括逐步减少运动症状的药物治疗,随后使用喹硫平或氯氮平。痴呆可用乙酰胆碱酯酶抑制剂治疗。关于PD患者抑郁的最佳药物治疗缺乏证据,专家意见表明选择性5-羟色胺再摄取抑制剂是首选的抗抑郁药。然而,迄今为止最大的一项研究发现,与安慰剂相比,去甲替林治疗有效,而控释帕罗西汀则无效。多种睡眠障碍可能困扰PD患者,治疗必须根据患者特定的睡眠障碍模式和相关因素进行个体化。吞咽障碍可能导致误吸和肺炎,吞咽困难的患者应转诊给言语治疗师进行进一步评估和治疗。体位性低血压可用非药物干预措施以及药物治疗(如氟氢可的松、米多君、吲哚美辛)。其他自主神经症状的处理方式与非PD患者相似,尽管在治疗胃肠功能障碍和胃轻瘫时必须注意避免使用多巴胺阻断疗法。
有多种药物和非药物策略可用于管理PD的非运动症状。鉴于PD的运动症状,不应忘记与非运动症状相关的挑战,应鼓励对非运动症状进行治疗。