Weintraub Daniel, Claassen Daniel O
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Parkinson's Disease and Mental Illness Research, Education and Clinical Centers, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States.
Vanderbilt University School of Medicine, Nashville, TN, United States.
Int Rev Neurobiol. 2017;133:679-717. doi: 10.1016/bs.irn.2017.04.006. Epub 2017 Jun 1.
Impulse control disorders (ICDs), such as compulsive gambling, buying, sexual, and eating behaviors, are a serious and increasingly recognized complication in Parkinson's disease (PD), occurring in up to 20% of PD patients over the course of their illness. Related behaviors include punding (stereotyped, repetitive, purposeless behaviors), dopamine dysregulation syndrome (DDS) (compulsive medication overuse), and hobbyism (e.g., compulsive internet use, artistic endeavors, and writing). These disorders have a significant impact on quality of life and function, strain interpersonal relationships, and worsen caregiver burden, and are associated with significant psychiatric comorbidity. ICDs have been most closely related to the use of dopamine agonists (DAs), while DDS is primarily associated with shorter acting, higher potency dopamine replacement therapy (DRT), such as levodopa. However, in preliminary research ICDs have also been reported to occur with monoamine oxidase inhibitor-B and amantadine treatment, and after deep brain stimulation (DBS) surgery. Other risk factors for ICDs may include sex (e.g., male sex for compulsive sexual behavior, and female sex for compulsive buying behavior); younger age overall at PD onset; a pre-PD history of an ICD; personal or family history of substance abuse, bipolar disorder, or gambling problems; and impulsive personality traits. Dysregulation of the mesocorticolimbic dopamine system is thought to be the major neurobiological substrate for ICDs in PD, but there is preliminary evidence for alterations in opiate and serotonin systems too. The primary treatment of ICDs in PD is discontinuation of the offending treatment, but not all patients can tolerate this due to worsening motor symptoms or DA withdrawal syndrome. While psychiatric medications and psychosocial treatments are frequently used to treat ICDs in the general population, there is limited empirical evidence for their use in PD, so it is critical for patients to be monitored closely for ICDs from disease onset and routine throughout its course. In the future, it may be possible to use a precision medicine approach to decrease the incidence of ICDs in PD by avoiding DA use in patients determined to be at highest risk based on their clinical and neurobiological (e.g., motor presentation, behavioral measures of medication response, genetics, dopamine transporter neuroimaging) profile. Additionally, as empirically validated treatments for ICDs and similar disorders (e.g., substance use disorders) emerge, it will also be important to examine their efficacy and tolerability in individuals with comorbid PD.
冲动控制障碍(ICDs),如强迫性赌博、购物、性行为和饮食行为,是帕金森病(PD)中一种严重且日益被认识到的并发症,在疾病过程中高达20%的PD患者会出现。相关行为包括刻板行为(刻板、重复、无目的的行为)、多巴胺调节障碍综合征(DDS)(强迫性药物过度使用)和嗜好成瘾(如强迫性上网、艺术活动和写作)。这些障碍对生活质量和功能有重大影响,给人际关系带来压力,加重照顾者负担,并且与显著的精神共病有关。ICDs与多巴胺激动剂(DAs)的使用关系最为密切,而DDS主要与作用时间较短、效力较高的多巴胺替代疗法(DRT),如左旋多巴有关。然而,在初步研究中,也有报告称ICDs发生在单胺氧化酶抑制剂 - B和金刚烷胺治疗期间,以及深部脑刺激(DBS)手术后。ICDs的其他危险因素可能包括性别(如强迫性行为多发生于男性,强迫购物行为多发生于女性);PD发病时总体年龄较轻;PD发病前有ICD病史;个人或家族有药物滥用、双相情感障碍或赌博问题的病史;以及冲动型人格特质。中脑边缘多巴胺系统失调被认为是PD中ICDs的主要神经生物学基础,但也有初步证据表明阿片类和5 - 羟色胺系统也存在改变。PD中ICDs的主要治疗方法是停用引起问题的治疗药物,但由于运动症状恶化或多巴胺戒断综合征,并非所有患者都能耐受。虽然精神科药物和心理社会治疗在普通人群中常用于治疗ICDs,但在PD中的应用经验证据有限,因此从疾病发作开始并在整个病程中对患者进行密切监测以发现ICDs至关重要。未来,有可能采用精准医学方法,通过避免在根据临床和神经生物学(如运动表现、药物反应的行为指标、遗传学、多巴胺转运体神经影像学)特征确定为最高风险的患者中使用DAs,来降低PD中ICDs的发生率。此外,随着针对ICDs和类似障碍(如物质使用障碍)的经验证治疗方法的出现,研究它们在合并PD个体中的疗效和耐受性也将很重要。