Lu Christine Y, Zhang Fang, Lakoma Matthew D, Butler Melissa G, Fung Vicki, Larkin Emma K, Kharbanda Elyse O, Vollmer William M, Lieu Tracy, Soumerai Stephen B, Chen Wu Ann
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts.
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts.
Clin Ther. 2015 Jun 1;37(6):1280-91. doi: 10.1016/j.clinthera.2015.03.027. Epub 2015 Apr 25.
In 2009, the US Food and Drug Administration (FDA) mandated a label change for leukotriene inhibitors (LTIs) to include neuropsychiatric adverse events (eg, depression and suicidality) as a precaution. This study investigated how this label change affected the use of LTIs and other asthma controller medications, mental health visits, and suicide attempts.
We analyzed data (2005-2010) from 5 large health plans in the US Population-Based Effectiveness in Asthma and Lung Diseases (PEAL) Network. The study cohort included children and adolescents (n = 30,000), young adults (n = 20,000), and adults (n = 90,000) with asthma. We used interrupted time series to examine changes in rates of LTI dispensings, non-LTI dispensings, mental health visits, and suicide attempts (using a validated algorithm based on a combination of diagnoses of injury or poisoning and psychiatric conditions).
The label change was associated with abrupt reductions in LTI use among all age groups (relative reductions of 8.3%, 15.1%, and 6.0% among adolescents, young adults, and adults, respectively, compared with expected rates at 1 year after the warnings). Although we detected immediate offset increases in non-LTI asthma medication use, these increases were not sustained among adolescents and young adults. There were small increases in mental health visits among LTI users.
The FDA label change for LTIs communicated possible risk of neuropsychiatric events. Communication and enhanced awareness may have increased reporting of mental health symptoms among young adults and adults. It is important to assess intended and unintended consequences of FDA warnings and label changes.
2009年，美国食品药品监督管理局（FDA）要求对白三烯抑制剂（LTI）的标签进行更改，将神经精神方面的不良事件（如抑郁和自杀倾向）作为一项预防措施列入其中。本研究调查了这一标签更改如何影响LTI及其他哮喘控制药物的使用、心理健康就诊情况以及自杀未遂事件。
我们分析了美国哮喘和肺部疾病人群有效性（PEAL）网络中5个大型健康计划的数据（2005 - 2010年）。研究队列包括患有哮喘的儿童和青少年（n = 30,000）、青年（n = 20,000）和成年人（n = 90,000）。我们使用中断时间序列来研究LTI配药率、非LTI配药率、心理健康就诊率和自杀未遂事件（使用基于伤害或中毒诊断与精神疾病诊断相结合的经验证算法）的变化。
标签更改与所有年龄组中LTI使用量的突然减少相关（与警告发出后1年的预期使用率相比，青少年、青年和成年人的相对减少率分别为8.3%、15.1%和6.0%）。尽管我们检测到非LTI哮喘药物使用量立即出现抵消性增加，但这些增加在青少年和青年中并未持续。LTI使用者的心理健康就诊量有小幅增加。
FDA对白三烯抑制剂的标签更改传达了神经精神事件的潜在风险。沟通和意识增强可能增加了青年和成年人中心理健康症状的报告。评估FDA警告和标签更改的预期和非预期后果很重要。
