PolicyLab, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania2Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia3Division of General Pediatrics, The Children's Hospital of Philadelphia, Phi.
PolicyLab, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
JAMA Pediatr. 2015 Apr;169(4):e150285. doi: 10.1001/jamapediatrics.2015.0285. Epub 2015 Apr 6.
Second-generation antipsychotics (SGAs) have increasingly been prescribed to Medicaid-enrolled children, either singly or in a medication combination. Although metabolic adverse effects have been linked to SGA use in youths, estimating the risk for type 2 diabetes mellitus, a rarer outcome, has been challenging.
To determine whether SGA initiation was associated with an increased risk for incident type 2 diabetes mellitus. Secondary analyses examined the risk associated with multiple-drug regimens, including stimulants and antidepressants, as well as individual SGAs.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective national cohort study of Medicaid-enrolled youths between January 2003 and December 2007. In this observational study using national Medicaid Analytic eXtract data files, initiators and noninitiators of SGAs were identified in each month. Included in this study were US youths aged 10 to 18 years with a mental health diagnosis and enrolled in a Medicaid fee-for-service arrangement during the study. Those with chronic steroid exposure, a diagnosis of diabetes mellitus, or SGA use during a 1-year look-back period were ineligible. The mean follow-up time for all participants was 17.2 months. Youths were followed up until diagnosis of diabetes mellitus or end of follow-up owing to censoring caused by the transition into a Medicaid managed care arrangement or Medicaid ineligibility (the end of available data). Propensity weights were developed to balance observed demographic and clinical characteristics between exposure groups. Discrete failure time models were fitted using weighted logistic regression to estimate the risk for incident diabetes mellitus between initiators and noninitiators.
A filled SGA prescription.
Incident type 2 diabetes mellitus identified through visit and pharmacy claims during the observation period.
Among 107,551 SGA initiators and 1,221,434 noninitiators, the risk for incident diabetes mellitus was increased among initiators (odds ratio [OR], 1.51; 95% CI, 1.35-1.69; P < .001). Compared with youths initiating only SGAs, the risk was higher among SGA initiators who used antidepressants concomitantly at the time of SGA initiation (OR, 1.54; 95% CI, 1.17-2.03; P = .002) but was not significantly different for SGA initiators who were concomitantly using stimulants. As compared with a reference group of risperidone initiators, the risk was higher among those initiating ziprasidone (OR, 1.61; 95% CI, 0.99-2.64; P = .06) and aripiprazole (OR, 1.58; 95% CI, 1.21-2.07; P = .001) but not quetiapine fumarate or olanzapine.
The risk for incident type 2 diabetes mellitus was increased among youths initiating SGAs and was highest in those concomitantly using antidepressants. Compared with risperidone, newer antipsychotics were not associated with decreased risk.
第二代抗精神病药物(SGAs)越来越多地被开给参加医疗补助计划的儿童,无论是单独使用还是与其他药物联合使用。尽管代谢不良反应与青少年使用 SGA 有关,但评估 2 型糖尿病这种罕见结果的风险一直具有挑战性。
确定 SGA 起始治疗是否与 2 型糖尿病发病风险增加相关。次要分析检查了与多种药物治疗方案(包括兴奋剂和抗抑郁药)以及个别 SGA 相关的风险。
设计、设置和参与者:这是一项针对 2003 年 1 月至 2007 年 12 月期间参加医疗补助计划的青少年的全国性回顾性队列研究。在这项使用全国性医疗补助分析提取数据文件的观察性研究中,每个月都会确定 SGA 的起始治疗者和非起始治疗者。本研究包括美国年龄在 10 至 18 岁之间、有精神健康诊断并在研究期间参加医疗补助服务收费安排的青少年。那些有慢性类固醇暴露、糖尿病诊断或在 1 年回顾期内使用 SGA 的患者不符合条件。所有参与者的平均随访时间为 17.2 个月。所有参与者都随访至糖尿病诊断或因过渡到医疗补助管理式医疗安排或医疗补助资格丧失(可用数据结束)而导致随访结束。为了平衡暴露组之间观察到的人口统计学和临床特征,开发了倾向权重。使用加权逻辑回归拟合离散失效时间模型,以估计起始治疗者和非起始治疗者之间新发糖尿病的风险。
填写的 SGA 处方。
通过观察期间的就诊和药房记录来确定 2 型糖尿病的发病情况。
在 107551 名 SGA 起始治疗者和 1221434 名非起始治疗者中,起始治疗者发生 2 型糖尿病的风险增加(比值比[OR],1.51;95%置信区间[CI],1.35-1.69;P<0.001)。与仅起始 SGA 的青少年相比,同时在 SGA 起始时使用抗抑郁药的 SGA 起始治疗者的风险更高(OR,1.54;95%CI,1.17-2.03;P=0.002),但同时使用兴奋剂的 SGA 起始治疗者的风险没有显著差异。与利培酮起始治疗者的参考组相比,起始治疗者使用齐拉西酮(OR,1.61;95%CI,0.99-2.64;P=0.06)和阿立哌唑(OR,1.58;95%CI,1.21-2.07;P=0.001)的风险更高,但喹硫平富马酸盐或奥氮平则不然。
开始使用 SGA 的青少年发生 2 型糖尿病的风险增加,同时使用抗抑郁药的风险最高。与利培酮相比,新型抗精神病药物与降低风险无关。