Department of Health Outcomes Research and Policy, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.
Biomedical Informatics Research Center, Marshfield Clinic Research Institute, Marshfield, WI, USA.
Drug Saf. 2018 Apr;41(4):363-376. doi: 10.1007/s40264-017-0624-0.
Several different types of drugs acting on the central nervous system (CNS) have previously been associated with an increased risk of suicide and suicidal ideation (broadly referred to as suicide). However, a differential association between brand and generic CNS drugs and suicide has not been reported.
This study compares suicide adverse event rates for brand versus generic CNS drugs using multiple sources of data.
Selected examples of CNS drugs (sertraline, gabapentin, zolpidem, and methylphenidate) were evaluated via the US FDA Adverse Event Reporting System (FAERS) for a hypothesis-generating study, and then via administrative claims and electronic health record (EHR) data for a more rigorous retrospective cohort study. Disproportionality analyses with reporting odds ratios and 95% confidence intervals (CIs) were used in the FAERS analyses to quantify the association between each drug and reported suicide. For the cohort studies, Cox proportional hazards models were used, controlling for demographic and clinical characteristics as well as the background risk of suicide in the insured population.
The FAERS analyses found significantly lower suicide reporting rates for brands compared with generics for all four studied products (Breslow-Day P < 0.05). In the claims- and EHR-based cohort study, the adjusted hazard ratio (HR) was statistically significant only for sertraline (HR 0.58; 95% CI 0.38-0.88).
Suicide reporting rates were disproportionately larger for generic than for brand CNS drugs in FAERS and adjusted retrospective cohort analyses remained significant only for sertraline. However, even for sertraline, temporal confounding related to the close proximity of black box warnings and generic availability is possible. Additional analyses in larger data sources with additional drugs are needed.
先前已有几种作用于中枢神经系统（CNS）的不同类型药物与自杀和自杀意念（广义上称为自杀）风险增加相关。然而，尚未报告品牌和仿制药 CNS 药物之间与自杀的差异关联。
本研究使用多种数据源比较品牌与仿制药 CNS 药物的自杀不良事件发生率。
通过美国 FDA 不良事件报告系统（FAERS）对 CNS 药物（舍曲林、加巴喷丁、唑吡坦和哌甲酯）的选定示例进行假设生成研究，然后通过行政索赔和电子健康记录（EHR）数据进行更严格的回顾性队列研究。在 FAERS 分析中，使用报告比值比和 95%置信区间（CI）进行不均衡性分析，以量化每种药物与报告自杀之间的关联。对于队列研究，使用 Cox 比例风险模型，控制人口统计学和临床特征以及参保人群自杀的背景风险。
FAERS 分析发现，与所有四种研究产品的仿制药相比，品牌的自杀报告率明显较低（Breslow-Day P <0.05）。在基于索赔和 EHR 的队列研究中，仅舍曲林的调整后危害比（HR）具有统计学意义（HR 0.58；95%CI 0.38-0.88）。
在 FAERS 和调整后的回顾性队列分析中，与品牌 CNS 药物相比，仿制药的自杀报告率不成比例地更高，仅舍曲林的结果仍然显著。然而，即使对于舍曲林，也可能存在与黑框警告和仿制药供应密切相关的时间性混杂。需要在更大的数据源中使用其他药物进行进一步分析。
