Long-term safety of methylphenidate in children with ADHD.
Long-term safety of methylphenidate in children with ADHD.
复制标题
哌醋甲酯治疗多动症儿童的长期安全性。
DOI：
10.1016/s2215-0366(23)00092-5
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Moran,LaurenV
中科院分区：
文献类型：
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作者：
Moran,LaurenV
哌甲酯治疗ADHD的短期疗效和安全性已经确定，但这种广泛使用的药物的长期安全性数据很少。在《柳叶刀精神病学》中，Kenneth Man及其同事试图通过对未使用兴奋剂的ADHD儿童和青少年进行前瞻性队列设计来填补这一空白：756名参与者开始接受哌甲酯治疗，391名参与者未接受哌甲酯治疗。[1]在为期2年的时间里，欧洲社区儿童和青少年精神卫生中心的研究人员使用一套全面的标准化评估，监测了参与者的生长轨迹以及心血管、精神和神经系统的结果，包括精神病、自杀、抽搐和物质使用。毫不奇怪，没有开始哌甲酯治疗的ADHD患者ADHD严重程度较低，并且不太可能患有其他精神疾病。在调整基线差异后，接受哌甲酯治疗的参与者在开始治疗后6个月体重增速下降，在2年随访期间的后期评估中不再明显。哌甲酯治疗与未治疗的受试者在精神或神经安全性结局方面的变化无差异。在2年的随访期内，接受哌甲酯治疗的受试者的心率、收缩压和舒张压均略有增加。鉴于过去的研究未发现服用兴奋剂的儿童和青少年发生严重心脏不良事件的风险增加，2在适当监测脉搏和血压的情况下，儿童和青少年长期使用哌醋甲酯治疗的风险似乎很小。这项研究增加了文献，因为缺乏哌甲酯的长期安全性数据。哌甲酯的随机对照试验时间较短，很少有研究评估超过12周的安全性。3行业赞助的试验通常包括过去使用兴奋剂的患者，4这可能会选择耐受兴奋剂的患者，导致高估安全性。通过将研究入组限制在未使用过兴奋剂的个体中，当前研究提供了额外的数据来支持哌甲酯在儿童和青少年中的安全性，并更好地反映现实世界的临床实践。然而，体重增加短期减速的发现在2年随访结束时不再存在，这与过去的研究不一致。ADHD多模式治疗研究（MTA）最初旨在测试哌甲酯在14个月内对儿童的有效性，并跟踪了一部分参与者。5根据使用足够剂量兴奋剂的持续时间对个体进行分类，以评估累积暴露对生长的影响。在12岁至15岁之间，持续使用兴奋剂的人和青春期使用兴奋剂可忽略不计的人的生长曲线出现分歧，持续使用兴奋剂的人在成年后的身高比使用兴奋剂可忽略不计的人降低。5此外，本研究的共同作者进行的荟萃分析确定了与哌甲酯相关的生长抑制超过2年。6
The short-term efficacy and safety of methylphenidate for the treatment of ADHD have been established but data on long-term safety of this widely used medication are scarce. In the Lancet Psychiatry, Kenneth Man and colleagues sought to fill this gap using a prospective cohort design in stimulant-naive children and adolescents with ADHD: 756 participants initiated treatment with methylphenidate and 391 were not treated with methylphenidate. 1 Using a comprehensive set of standardised assessments over a 2-year period, investigators at community-based child and adolescent mental health centres throughout Europe monitored growth trajectories of participants as well as cardiovascular, psychiatric, and neurological outcomes including psychosis, suicidality, tics, and substance use. Not surprisingly, patients with ADHD who were not initiated on methylphenidate had lower ADHD severity and were less likely to have other psychiatric comorbidities. After adjusting for baseline differences, participants treated with methylphenidate had decreased weight velocity 6 months after initiating treatment that was no longer apparent at later assessments during the 2-year follow-up period. There were no differences in changes in psychiatric or neurological safety outcomes between participants treated versus not treated with methylphenidate. Participants treated with methylphenidate had modest increases in heart rate and both systolic and diastolic blood pressure throughout the 2-year follow-up period. Given that past studies have found no increased risk of serious cardiac adverse events in children and adolescents taking stimulants, 2 with appropriate monitoring of pulse and blood pressure, long-term treatment with methylphenidate in children and adolescents appears to be of minimal risk. This study adds to the literature as there is a scarcity of long-term safety data on methylphenidate. Randomised controlled trials of methylphenidate are short, with few studies assessing safety for longer than 12 weeks. 3 Industry-sponsored trials often include patients with past stimulant use, 4 which could select for patients who tolerate stimulants leading to overestimating safety. By restricting study enrollment to stimulant-naive individuals, the current study provides additional data that support the safety of methylphenidate in children and adolescents and better reflect real-world clinical practice.However, the finding of short-term deceleration in weight gain that was no longer present at the end of the 2 year follow-up is inconsistent with past studies. The Multimodal Treatment of ADHD Study (MTA), which was initially designed to test the effectiveness of methylphenidate in children over a 14-month period, followed a subset of participants through young adulthood. 5 Individuals were classified based on duration of use of an adequate dose of stimulant to assess the effect of cumulative exposure on growth. Growth curves diverged for individuals who consistently used stimulants and those with negligible stimulant use during puberty, between the ages of 12 and 15 years, with individuals with consistent use of stimulants having decreased height in adulthood than those with negligible stimulant use. 5 In addition, a meta-analysis conducted by co-authors of the current study identified growth suppression associated with methylphenidate over a 2-year period. 6