Risks and Benefits of ADHD Medication for Psychiatric and Neurologic Problems

描述(申请人提供)：随机对照试验表明ADHD药物有有益的短期效果。然而，由于对ADHD药物的短期和长期影响的担忧，ADHD药物的越来越多的使用正受到激烈的辩论。这项建议的总体目标是通过在两个大型数据集中进行高级药物流行病学分析，更准确地估计ADHD药物对严重精神疾病(药物滥用、自杀行为、躁狂/双相情感障碍和严重抑郁症)和神经(癫痫/癫痫)结果的短期和长期风险和益处的程度，其中包括关于处方ADHD药物和医疗问题的前瞻性纵向信息。我们将使用根据国家登记诊断为ADHD的瑞典队列患者7.5万人。而且，我们将根据保险索赔对美国的大样本进行分析，其中包括230万ADHD患者。这两个数据集中的分析将使用相同的分析方法，包括个人内部比较和先进的统计技术，以解释稳定和时变的混淆。我们的中心假设是，ADHD药物治疗将与减少精神和神经问题有关，不良结果(例如短期癫痫发作和长期药物使用问题)的风险将很小，特别是当我们比较个体内部的关系时。第一个目标是检查ADHD药物对这些问题的短期影响。第二个目标是检查ADHD药物对这些问题的长期影响。这项拟议研究的基本原理是，严格的药物流行病学研究--采用先进的设计和大量人口样本的统计分析--可以更准确地表征ADHD药物的风险和益处。这项拟议的研究的意义在于，研究结果将更准确地确定与ADHD药物相关的特定风险和好处，而这些风险和好处是以前的研究无法充分探索的。拟议的分析基于两个大型数据集，还将探索这些发现在不同国家、文化和医学背景下的普适性。这些努力将直接为医疗实践提供信息，并影响许多领域的后续研究，如药物流行病学和随机对照试验。这项拟议的研究具有创新性，因为研究团队将分析两个数据集(瑞典和美国)；将个人内部比较与复杂的分析策略相结合，以排除混杂因素；并汇集一支在ADHD病因学和治疗、药物流行病学、准实验设计以及对这两个数据集的分析方面具有专业知识的国际研究团队。因此，我们建议对与ADHD药物相关的严重精神和神经学问题进行迄今为止最全面的研究。

DESCRIPTION (provided by applicant): Randomized controlled trials suggest that ADHD medication has beneficial short-term effects. The increasing use of ADHD medications is being heavily debated, however, because of concerns regarding the short- and long-term effects of ADHD medications. The overall objective for this proposal is to more precisely estimate the magnitude of the short- and long-term risks and benefits of ADHD medications on serious psychiatric (substance abuse, suicidal behavior, mania/bipolar disorder, and major depression) and neurological (seizures/epilepsy) outcomes by conducting advanced pharmaco-epidemiologic analyses in two large datasets that include prospective longitudinal information on prescribed ADHD medications and medical problems. We will use a Swedish cohort of 75,000 patients with a diagnosis of ADHD based on national registers. And, we will conduct analyses on a large US sample based on insurance claims, including 2.3 million patients with ADHD. The analyses in both datasets will use the same analytical approaches, including within-individual comparisons and advanced statistical techniques to account for stable and time-varying confounding. Our central hypothesis is that ADHD medication will be associated with reduced psychiatric and neurological problems and that risk for adverse outcomes (e.g., short-term seizures and long-term substance use problems) will be minor, especially when we compare the relations within individuals. The first aim is to examine the short-term effects of ADHD medications on these problems. The second aim is to examine the long-term effects of ADHD medications on these problems. The rationale for the proposed research is that rigorous pharmaco-epidemiologic studies-employing advanced designs and statistical analyses with large, population samples-can more precisely characterize the risks and benefits of ADHD medication. The significance of the proposed research is that the results will more precisely identify the specific risks and benefits associated with ADHD medication, which previous studies have been unable to adequately explore. The proposed analyses, which are based on the two large datasets, also will explore the generalizability of the findings across different national, cultural, and medical contexts. These efforts would directly inform medical practice and influence subsequent research in numerous fields, such as pharmaco-epidemiology and randomized controlled trials. The proposed research is innovative because the research team will analyze two datasets (in Sweden and the United States); combine within-individual comparisons with sophisticated analytical strategies to rule out confounding factors; and bring together a team of international researchers with expertise in the etiology and treatment of ADHD, pharmaco-epidemiology, quasi-experimental designs, and analyses of both datasets. We propose, therefore, to conduct the most comprehensive study of serious psychiatric and neurologic problems associated with ADHD medication to date.