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[使用哌甲酯治疗注意力缺陷多动障碍期间的心血管风险及管理]

[Cardiovascular risks and management during Attention Deficit Hyperactivity Disorder treatment with methylphenidate].

作者信息

Bange F, Le Heuzey M-F, Acquaviva E, Delorme R, Mouren M-C

机构信息

Service de psychiatrie de l'enfant et de l'adolescent, hôpital Robert-Debré, 48, boulevard Sérurier, 75019 Paris, France.

Service de psychiatrie de l'enfant et de l'adolescent, hôpital Robert-Debré, 48, boulevard Sérurier, 75019 Paris, France.

出版信息

Arch Pediatr. 2014 Jan;21(1):108-12. doi: 10.1016/j.arcped.2013.11.001. Epub 2013 Dec 3.

Abstract

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common of the pediatric neuropsychiatric disorders. Methylphenidate is an important element of therapeutic strategies for ADHD. Clinicians are interested in the safety of methylphenidate. Because this drug raises heart rate and blood pressure, concerns have been raised about its cardiovascular safety. Concerns were based on case reports of sudden cardiac death in methylphenidate users, plausible pharmacological pathways involving well-established stimulant effects on heart rate and blood pressure. Until recently, data were limited to a number of observational studies too small to examine serious cardiac events. In the past two years, large retrospective, population-based cohort studies were performed. These studies did not show any evidence that methylphenidate was associated with an increase in risk of myocardial infarction, sudden cardiac death, or stroke. Treatment of children with methylphenidate is not significantly associated with an increase in the short term or mid-term risk of severe cardiac events. For many, available data now will be seen as reassuring. But gaps persist in the methodical and comprehensive assessments of the safety of methylphenidate. Analyses cannot be generalized to children with long-term use of stimulants. Furthermore, long-term effects of slight increases in heart rate or blood pressure are unknown. Stimulant administration continues to have a detectable adrenergic effect even after years of treatment. In the MTA study, greater cumulative stimulant exposure was associated with a higher heart rate at years 3 and 8. Although less severe, such adverse cardiac events are nonetheless alarming to patients. This adrenergic effect may have clinical implications, especially for individual patients with underlying heart abnormalities and it deserves further investigation. More research is necessary to optimize a safe use of methylphenidate regarding its cardiovascular effects. In light of the controversies surrounding the increase in the number of children being diagnosed with ADHD, the broad use of methylphenidate in these patients, and cardiovascular concerns about it, this article addresses topics of clinical significance. For ease of use by practitioners, the article summarizes the guidelines stated by the European Medicines Agency over the appropriate pretreatment evaluation and cardiovascular assessment. It advocates a thorough history and physical examination before initiating methylphenidate to treat patients with ADHD, with an emphasis on the identification of risk factors for sudden death. A cardiac sub-specialist consultation is mandatory in case of history or physical examination findings. In other cases, an electrocardiographic screening is recommended in order to check out previously unrecognized heart disease.

摘要

注意缺陷多动障碍(ADHD)是最常见的儿科神经精神疾病之一。哌甲酯是ADHD治疗策略的重要组成部分。临床医生关注哌甲酯的安全性。由于这种药物会提高心率和血压,人们对其心血管安全性提出了担忧。这些担忧基于哌甲酯使用者猝死的病例报告,以及涉及对心率和血压有明确刺激作用的合理药理途径。直到最近,数据还仅限于一些规模太小无法检测严重心脏事件的观察性研究。在过去两年中,进行了大规模的基于人群的回顾性队列研究。这些研究没有显示任何证据表明哌甲酯与心肌梗死、猝死或中风风险增加有关。用哌甲酯治疗儿童与短期或中期严重心脏事件风险增加没有显著关联。对许多人来说,现有的数据现在会被视为令人安心的。但在哌甲酯安全性的系统和全面评估方面仍然存在差距。分析不能推广到长期使用兴奋剂的儿童。此外,心率或血压轻微升高的长期影响尚不清楚。即使经过多年治疗,兴奋剂给药仍有可检测到的肾上腺素能效应。在多模式治疗研究(MTA)中,累积兴奋剂暴露量越大,在第3年和第8年时心率越高。尽管不那么严重,但这种不良心脏事件对患者来说仍然令人担忧。这种肾上腺素能效应可能具有临床意义,特别是对于有潜在心脏异常的个体患者,值得进一步研究。需要更多研究来优化哌甲酯在心血管方面的安全使用。鉴于围绕被诊断患有ADHD的儿童数量增加、哌甲酯在这些患者中的广泛使用以及对其心血管方面的担忧存在争议,本文讨论了具有临床意义的话题。为便于从业者使用,本文总结了欧洲药品管理局关于适当的预处理评估和心血管评估的指南。它主张在开始使用哌甲酯治疗ADHD患者之前进行全面的病史和体格检查,重点是识别猝死的危险因素。如果有病史或体格检查结果,必须进行心脏专科会诊。在其他情况下,建议进行心电图筛查以检查出先前未被识别的心脏病。

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