From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston (L.V.M., S.S.); the Division of Psychotic Disorders, McLean Hospital, Belmont, MA (L.V.M., D.O.); and the Department of Health Care Policy (J.H.), Harvard Medical School (L.V.M., D.O., J.H., R.H.P., S.S.), the Mongan Institute Health Policy Center (J.H.) and the Center for Quantitative Health, Department of Psychiatry (R.H.P.), Massachusetts General Hospital, and Partners Research Computing, Partners HealthCare System (V.M.C.) - all in Boston.
N Engl J Med. 2019 Mar 21;380(12):1128-1138. doi: 10.1056/NEJMoa1813751.
The prescription use of the stimulants methylphenidate and amphetamine for the treatment of attention deficit-hyperactivity disorder (ADHD) has been increasing. In 2007, the Food and Drug Administration mandated changes to drug labels for stimulants on the basis of findings of new-onset psychosis. Whether the risk of psychosis in adolescents and young adults with ADHD differs among various stimulants has not been extensively studied.
We used data from two commercial insurance claims databases to assess patients 13 to 25 years of age who had received a diagnosis of ADHD and who started taking methylphenidate or amphetamine between January 1, 2004, and September 30, 2015. The outcome was a new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis. To estimate hazard ratios for psychosis, we used propensity scores to match patients who received methylphenidate with patients who received amphetamine in each database, compared the incidence of psychosis between the two stimulant groups, and then pooled the results across the two databases.
We assessed 337,919 adolescents and young adults who received a prescription for a stimulant for ADHD. The study population consisted of 221,846 patients with 143,286 person-years of follow up; 110,923 patients taking methylphenidate were matched with 110,923 patients taking amphetamines. There were 343 episodes of psychosis (with an episode defined as a new diagnosis code for psychosis and a prescription for an antipsychotic medication) in the matched populations (2.4 per 1000 person-years): 106 episodes (0.10%) in the methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard ratio with amphetamine use, 1.65; 95% confidence interval, 1.31 to 2.09).
Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients. Amphetamine use was associated with a greater risk of psychosis than methylphenidate. (Funded by the National Institute of Mental Health and others.).
用于治疗注意缺陷多动障碍（ADHD）的兴奋剂哌醋甲酯和安非他命的处方使用量一直在增加。2007 年，美国食品和药物管理局根据新出现的精神病学发现，要求改变兴奋剂的药物标签。在患有 ADHD 的青少年和年轻成年人中，各种兴奋剂的精神病发病风险是否存在差异，尚未得到广泛研究。
我们使用来自两个商业保险索赔数据库的数据，评估了在 2004 年 1 月 1 日至 2015 年 9 月 30 日期间接受 ADHD 诊断且开始服用哌醋甲酯或安非他命的 13 至 25 岁的患者。结果是在精神病发作后的 60 天内开出了抗精神病药物的新诊断为精神病。为了估计精神病的风险比，我们使用倾向评分在每个数据库中将接受哌醋甲酯的患者与接受安非他命的患者进行匹配，比较两组兴奋剂之间的精神病发生率，然后将两个数据库的结果汇总。
我们评估了 337919 名接受 ADHD 兴奋剂处方的青少年和年轻成年人。研究人群包括 221846 名患者，随访 143286 人年；110923 名服用哌醋甲酯的患者与 110923 名服用安非他命的患者相匹配。在匹配人群中，有 343 例精神病发作（以新诊断为精神病和抗精神病药物处方的新诊断代码为定义）（每 1000 人年 2.4 例）：哌醋甲酯组 106 例（0.10%），安非他命组 237 例（0.21%）（安非他命使用的危险比，1.65；95%置信区间，1.31 至 2.09）。
在接受处方兴奋剂治疗的 ADHD 青少年和年轻成年人中，新发精神病的发病率约为每 660 名患者中就有 1 例。与哌醋甲酯相比，安非他命的使用与精神病的风险增加相关。（由美国国家心理健康研究所等资助）。
