Burcu Mehmet, Zito Julie M, Safer Daniel J, Magder Laurence S, dosReis Susan, Shaya Fadia T, Rosenthal Geoffrey L
1 Department of Pharmaceutical Health Services Research, University of Maryland , Baltimore, Baltimore, Maryland.
2 Department of Psychiatry, University of Maryland , Baltimore, Baltimore, Maryland.
J Child Adolesc Psychopharmacol. 2018 Sep;28(7):445-453. doi: 10.1089/cap.2017.0121. Epub 2018 Jul 5.
To assess the risk of incident cardiovascular events that led to hospitalizations or emergency department visits following atypical antipsychotic (AAP) treatment initiation in youth according to dose, duration of use, and concomitant use of leading psychotropic medication classes.
We used computerized Medicaid claims to conduct a retrospective cohort study of youth (5-20 years) who initiated AAP treatment. AAP use was operationalized in a time-dependent manner according to current vs. former use, average daily dose (in risperidone dose equivalents), and duration of use. In a secondary analysis, concomitant use of (1) stimulants and (2) serotonin-reuptake inhibitors (SSRI/SNRIs) with AAPs was also assessed. To account for confounding, disease risk score methodology was used in discrete time failure models.
There were 74,700 youth who initiated AAP treatment (average follow-up = 24.8 months). During follow-up, the risk of cardiovascular events was significantly greater during current than former AAP use (RR = 1.55, 95% CI = 1.09-2.21). Furthermore, for current users of AAPs, the risk of cardiovascular events intensified with average daily dose (RR = 2.04, 95% CI = 1.11-3.77 for >3.75 mg/day vs. ≤1.25 mg/day). The risk of cardiovascular events did not significantly differ according to duration of AAP use. In AAP-treated youth, concomitant SSRI/SNRI use was associated with an increased risk of cardiovascular events (RR = 1.61, 95% CI = 1.01-2.57). By contrast, stimulant use concomitant with AAPs was not significantly associated with an increased risk of cardiovascular events.
In publicly insured U.S. youth, current AAP use was associated with an increased risk of incident cardiovascular events, which intensified with increasing dose and with concomitant SSRI/SNRI use. Prudent interpretation of these findings suggests that further research is needed to identify youth subpopulations with the greatest risk of developing AAP treatment-emergent cardiovascular events.
根据剂量、使用时长以及主要精神类药物的联合使用情况，评估青少年开始使用非典型抗精神病药物（AAP）后发生导致住院或急诊就诊的心血管事件的风险。
我们利用医疗补助计划的计算机化索赔数据，对开始使用AAP治疗的青少年（5 - 20岁）进行回顾性队列研究。AAP的使用根据当前使用与既往使用情况、平均日剂量（以利培酮等效剂量计）以及使用时长进行时间依赖性操作化定义。在二次分析中，还评估了（1）兴奋剂和（2）5-羟色胺再摄取抑制剂（SSRI/SNRI）与AAP的联合使用情况。为了控制混杂因素，在离散时间失败模型中使用疾病风险评分方法。
有74,700名青少年开始使用AAP治疗（平均随访时间 = 24.8个月）。在随访期间，当前使用AAP时心血管事件的风险显著高于既往使用AAP时（风险比[RR]=1.55，95%置信区间[CI]=1.09 - 2.21）。此外，对于当前使用AAP的患者，心血管事件的风险随平均日剂量增加而增强（对于每日剂量>3.75毫克/天与≤1.25毫克/天相比，RR = 2.04，95% CI = 1.11 - 3.77）。心血管事件的风险根据AAP使用时长无显著差异。在接受AAP治疗的青少年中，联合使用SSRI/SNRI与心血管事件风险增加相关（RR = 1.61，95% CI = 1.01 - 2.57）。相比之下，AAP与兴奋剂联合使用与心血管事件风险增加无显著关联。
在美国有公共保险的青少年中，当前使用AAP与心血管事件发生风险增加相关，该风险随剂量增加以及联合使用SSRI/SNRI而增强。对这些研究结果的审慎解读表明，需要进一步研究以确定发生AAP治疗引发的心血管事件风险最高的青少年亚组。
