Burcu Mehmet, Zito Julie M, Safer Daniel J, Magder Laurence S, dosReis Susan, Shaya Fadia T, Rosenthal Geoffrey L
Department of Pharmaceutical Health Services Research, University of Maryland, Baltimore.
Department of Psychiatry, University of Maryland, Baltimore.
JAMA Pediatr. 2017 Dec 1;171(12):1200-1207. doi: 10.1001/jamapediatrics.2017.2896.
Antidepressants are one of the most commonly prescribed classes of psychotropic medications among US youths. For adults, there is emerging evidence on the increased risk of type 2 diabetes in association with antidepressant use. However, little is known about the antidepressant treatment-emergent risk of type 2 diabetes among youths.
To assess the association between antidepressant use and the risk of incident type 2 diabetes in youths by antidepressant subclass and according to duration of use, cumulative dose, and average daily dose.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted using Medicaid claims data from 4 geographically diverse, large states of youths 5 to 20 years of age who initiated antidepressant treatment from January 1, 2005, to December 31, 2009.
Antidepressant use (selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs], tricyclic or other cyclic antidepressants, and other antidepressants) was assessed using the following 4 time-varying measures: current or former use, duration of use, cumulative dose, and average daily dose.
Incident type 2 diabetes was assessed using discrete-time failure models, adjusting for disease risk score estimated using more than 125 baseline and time-dependent covariates.
In this cohort of 119 608 youths aged 5 to 20 years who initiated antidepressant treatment (59 087 female youths and 60 521 male youths; 54.7% between 5 and 14 years of age) with a mean follow-up of 22.8 months, 79 285 [66.3%] had SSRI or SNRI exposure. The risk of type 2 diabetes was significantly greater during current use than former use of SSRIs or SNRIs (absolute risk, 1.29 per 10 000 person-months vs 0.64 per 10 000 person-months; adjusted relative risk [RR], 1.88; 95% CI, 1.34-2.64) and tricyclic or other cyclic antidepressants (absolute risk, 0.89 per 10 000 person-months vs 0.48 per 10 000 person-months; RR, 2.15; 95% CI, 1.06-4.36), but not of other antidepressants (absolute risk, 1.15 per 10 000 person-months vs 1.12 per 10 000 person-months; RR, 0.99; 95% CI, 0.66-1.50). Furthermore, for youths currently using SSRIs or SNRIs, the risk of type 2 diabetes increased with the duration of use (RR, 2.66; 95% CI, 1.45-4.88 for >210 days and RR, 2.56; 95% CI, 1.29-5.08 for 151-210 days compared with 1-90 days) and with the cumulative dose (RR, 2.44; 95% CI, 1.35-4.43 for >4500 mg and RR, 2.17; 95% CI, 1.07-4.40 for 3001-4500 mg compared with 1-1500 mg in fluoxetine hydrochloride dose equivalents). By contrast, neither the duration nor the cumulative dose of other antidepressants was associated with an increased risk of type 2 diabetes. The risk of type 2 diabetes increased significantly with the average daily dose among youths with more than 150 days of SSRI or SNRI use (RR, 2.39; 95% CI, 1.04-5.52 for >15.0 vs ≤15.0 mg/d) but not among youths with 1 to 150 days of SSRI or SNRI use.
In a large cohort of youths insured by Medicaid, the use of SSRIs or SNRIs-the most commonly used antidepressant subclass-was associated with an increased risk of type 2 diabetes that intensified with increasing duration of use, cumulative dose, and average daily dose.
抗抑郁药是美国青少年中最常处方的精神类药物之一。对于成年人，有新出现的证据表明使用抗抑郁药会增加患2型糖尿病的风险。然而，关于青少年使用抗抑郁药后出现2型糖尿病的风险却知之甚少。
按抗抑郁药亚类以及使用持续时间、累积剂量和日均剂量评估青少年使用抗抑郁药与发生2型糖尿病风险之间的关联。
设计、设置和参与者：一项回顾性队列研究使用了来自4个地理位置不同的大州的医疗补助索赔数据，这些数据涉及2005年1月1日至2009年12月31日开始接受抗抑郁治疗的5至20岁青少年。
使用以下4种随时间变化的测量方法评估抗抑郁药的使用情况（选择性5-羟色胺再摄取抑制剂[SSRI]或5-羟色胺-去甲肾上腺素再摄取抑制剂[SNRI]、三环或其他环类抗抑郁药以及其他抗抑郁药）：当前或以前使用情况、使用持续时间、累积剂量和日均剂量。
使用离散时间失效模型评估2型糖尿病的发生情况，并根据使用超过125个基线和随时间变化的协变量估计的疾病风险评分进行调整。
在这个队列中，119608名5至20岁开始接受抗抑郁治疗的青少年（59087名女性青少年和60521名男性青少年；其中54.7%年龄在5至14岁之间）平均随访22.8个月，79285名（66.3%）曾暴露于SSRI或SNRI。当前使用SSRI或SNRI期间患2型糖尿病的风险显著高于以前使用期间（绝对风险，每10000人月1.29例 vs 每10000人月0.64例；调整后相对风险[RR]，1.88；95%置信区间[CI]，1.34 - 2.64）以及三环或其他环类抗抑郁药（绝对风险，每10000人月0.89例 vs 每10000人月0.48例；RR，2.15；95%CI，1.06 - 4.36），但其他抗抑郁药并非如此（绝对风险，每10000人月1.15例 vs 每10000人月1.12例；RR，0.99；95%CI，0.66 - 1.50）。此外，对于当前使用SSRI或SNRI的青少年，患2型糖尿病的风险随使用持续时间增加（与1 - 90天相比，使用>210天的RR为2.66；95%CI，1.45 - 4.88，使用151 - 210天的RR为2.56；95%CI，1.29 - 5.08）以及累积剂量增加（与1 - 1500毫克盐酸氟西汀等效剂量相比，使用>4500毫克的RR为2.44；95%CI，1.35 - 4.43，使用3001 - 4500毫克的RR为2.17；95%CI，1.07 - 4.40）而增加。相比之下，其他抗抑郁药的使用持续时间和累积剂量均与2型糖尿病风险增加无关。在使用SSRI或SNRI超过150天的青少年中，2型糖尿病风险随日均剂量显著增加（与≤15.0毫克/天相比，>15.0毫克/天的RR为2.39；95%CI，1.04 - 5.52），但在使用SSRI或SNRI 1至150天的青少年中并非如此。
在一个由医疗补助承保的大量青少年队列中，使用最常用的抗抑郁药亚类SSRI或SNRI与2型糖尿病风险增加相关，且随着使用持续时间、累积剂量和日均剂量的增加而加剧。
