Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Québec, Canada; Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Québec, Canada.
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Québec, Canada.
J Affect Disord. 2022 Dec 1;318:231-237. doi: 10.1016/j.jad.2022.08.094. Epub 2022 Sep 6.
Selective serotonin reuptake inhibitors (SSRIs) have been associated with type 2 diabetes mellitus (T2DM) in youths, possibly via 5-HT, H receptors and serotonin transporter (SERT). SSRIs have similar affinity for SERT but variable affinity for 5-HT and H. This study assessed whether SSRIs with strong affinity for 5-HT and H (relative to SERT) were associated with T2DM risk compared with weak-affinity SSRIs.
Using the UK Clinical Practice Research Datalink, we assembled a cohort of patients aged 5-24, newly prescribed a strong-affinity SSRI (citalopram, escitalopram, fluoxetine) or weak affinity (paroxetine, sertraline, fluvoxamine) between 1990 and 2019. We controlled for confounding using standardized mortality ratio weighting, estimated from calendar time-specific propensity scores. We used weighted Cox proportional hazards models to estimate hazard ratios (HRs) of incident T2DM with 95 % confidence intervals (CIs).
The cohort included 347,368 new users of strong-affinity SSRIs and 131,359 of weak-affinity SSRIs. Strong-affinity SSRIs were not associated with an increased T2DM risk compared with weak-affinity SSRIs (incidence rate 2.8 vs 2.7 per 1000 person-years; HR 1.03, 95 % CI 0.85-1.25). T2DM risk did not vary with duration of use, age or sex. However, the HR was numerically higher in youths with normal or low weight (HR 1.30, 95 % CI 0.85-1.98) and with prior antipsychotic use (HR 1.62, 95 % CI 0.83-3.18).
Median duration of SSRI use, in line with real-world SSRI prescribing, was relatively short.
T2DM risk did not differ between strong- and weak-affinity SSRIs, providing reassurance for clinicians when choosing between SSRIs in youths.
选择性 5-羟色胺再摄取抑制剂（SSRIs）与青少年 2 型糖尿病（T2DM）有关，可能通过 5-HT、H 受体和血清素转运体（SERT）。SSRIs 对 SERT 具有相似的亲和力，但对 5-HT 和 H 的亲和力不同。本研究评估了与弱亲和力 SSRIs 相比，对 5-HT 和 H（相对于 SERT）具有强亲和力的 SSRIs 是否与 T2DM 风险相关。
使用英国临床实践研究数据链接，我们组建了一个年龄在 5-24 岁之间、1990 年至 2019 年间新处方强亲和力 SSRIs（西酞普兰、艾司西酞普兰、氟西汀）或弱亲和力 SSRIs（帕罗西汀、舍曲林、氟伏沙明）的患者队列。我们使用标准化死亡率比加权法进行混杂因素控制，该方法是根据特定日历时间的倾向评分估算的。我们使用加权 Cox 比例风险模型估计 T2DM 发生率的风险比（HR）及其 95%置信区间（CI）。
队列包括 347368 名新使用强亲和力 SSRIs 的患者和 131359 名新使用弱亲和力 SSRIs 的患者。与弱亲和力 SSRIs 相比，强亲和力 SSRIs 与 T2DM 风险增加无关（发病率为每 1000 人年 2.8 例 vs 2.7 例；HR 1.03，95%CI 0.85-1.25）。T2DM 风险与使用时间、年龄或性别无关。然而，在体重正常或偏低的青少年（HR 1.30，95%CI 0.85-1.98）和有既往抗精神病药物使用史的患者（HR 1.62，95%CI 0.83-3.18）中，HR 数值较高。
SSRIs 的使用中位数与真实世界的 SSRIs 处方一致，相对较短。
强亲和力 SSRIs 和弱亲和力 SSRIs 之间的 T2DM 风险没有差异，为临床医生在青少年中选择 SSRIs 时提供了保证。
