Risk Factors for Psychosis and Mania with Prescription Amphetamine Use

文摘：处方安非他明在治疗注意缺陷多动障碍中的应用 (ADHD)在过去15年中显著增加，青少年和青少年的增加幅度最大。 成年人。2007年，FDA要求更改兴奋剂标签，以警告精神病和躁狂症的增加。 没有既往疾病的患者。我们来自布里格姆和女子大学的多学科研究团队 医院和McLean医院最近发表了一项里程碑式的队列研究，表明 青少年和青年苯丙胺新使用者与哌醋甲酯患者的精神病发作比较 患有多动症的成年人。令人震惊的是，安非他明的使用量在研究期间增加了四倍(2004- 2015年)。此外，我们的数据显示，处方安非他明在患者中的使用大幅增加 患有先前存在的双相情感障碍。因此，迫切需要加快对处方者水平的了解 增加精神病和躁狂症风险的因素、患者水平的因素和疾病状态 处方安非他明。使用真实数据进行大规模研究是研究糖尿病风险的唯一选择 罕见且严重的不良后果。在目标1中，使用事件-用户队列研究设计，我们将利用 来自两个国家行政索赔数据库的数据，以确定增加 约220,000名患有ADHD的青少年和成人服用安非他明后出现首发精神病的风险。我们 假设精神病的风险会有剂量依赖性的增加。目标2的目标是 确定使用处方安非他明的精神病/躁狂风险较高的患者亚群。至 为了实现这一目标，我们将使用电子病历(EMR)进行病例对照研究 McLean医院在约1,650名因精神病或躁狂症首次发作而住院的患者中与 约3,300名对照，首次因精神病或躁狂症以外的原因住院治疗。我们会申请 对非结构化叙述性笔记进行自然语言处理，以捕获中未提供的详细患者数据 索赔数据。我们假设有精神疾病家族史的患者将有更高的风险 与没有家族史的患者相比，服用安非他明的患者患精神病/躁狂症的风险更高。我们还假设 同时吸食大麻的患者患精神错乱/安非他明躁狂症的风险增加 与不使用大麻的患者相比。目标3比较了约52,000人中接受治疗的风险--突发躁狂症 既往双相情感障碍患者队列研究中苯丙胺与哌醋甲酯的新使用者 无序，这是一个紧迫的问题，因为使用兴奋剂存在躁狂的已知风险。综合起来，这些研究将 提供可操作的证据，纳入临床实践指南，目的是减轻 服用处方兴奋剂有精神错乱和躁狂的风险。建议的研究议程与NIMH一致 关于在实际实践环境中测试干预措施的战略目标3.3“努力预防和治疗” 评估患者和提供者水平的因素对临床结果的影响。

ABSTRACT: The use of prescription amphetamines for the treatment of attention-deficit hyperactivity disorder (ADHD) has markedly increased in the last fifteen years, with the greatest increase in adolescents and young adults. In 2007, the FDA mandated changes to stimulant labels to warn of increases in psychosis and mania in patients without pre-existing conditions. Our multidisciplinary research team from Brigham and Women's Hospital and McLean Hospital recently published a landmark cohort study demonstrating an increased risk of psychotic episodes in new users of amphetamine compared to methylphenidate in adolescents and young adults with ADHD. Alarmingly, the use of amphetamines increased four-fold over the study period (2004 – 2015). In addition, our data show that prescription amphetamine use has dramatically increased in patients with pre-existing bipolar disorder. Thus, there is an urgent need to accelerate knowledge about prescriber-level factors, patient-level factors and disease states that potentiate the risk of psychosis and mania with prescription amphetamines. Large-scale studies using real-world data are the only option to study the risk of infrequent and serious adverse outcomes. In Aim 1, using incident-user cohort study designs, we will utilize data from two national administrative claims databases to identify prescriber dosing strategies that increase the risk of first-episode psychosis in ~220,000 adolescents and adults with ADHD initiating amphetamines. We hypothesize that there will be a dose-dependent increase in the risk of psychosis. The goal of Aim 2 is to identify patient subgroups at heightened risk of psychosis/mania with prescription amphetamine use. To accomplish this goal, we will perform a case control study using electronic medical records (EMR) from McLean Hospital in ~1,650 patients hospitalized for an initial episode of psychosis or mania compared to ~3,300 controls with a first psychiatric hospitalization for reasons other than psychosis or mania. We will apply natural language processing to unstructured narrative notes to capture detailed patient data not available in claims data. We hypothesize that patients with a family history of psychiatric illness will have an increased risk of psychosis/mania with amphetamines compared to patients without a family history. We also hypothesize that patients with concurrent cannabis use will have an increased risk of psychosis/mania with amphetamines compared to patients without cannabis use. Aim 3 compares the risk of treatment-emergent mania in ~52,000 new users of amphetamine versus methylphenidate in a cohort study of patients with pre-existing bipolar disorder, an urgent issue given the known risk of mania with stimulant use. Combined, these studies will provide actionable evidence to be incorporated into clinical practice guidelines with the goal of mitigating the risk of psychosis and mania with prescription stimulants. The proposed research agenda aligns with NIMH Strategic Objective 3.3 “Striving for Prevention and Cure” on testing interventions in real-world practice settings to evaluate the impact of patient- and provider-level factors on clinical outcomes.