Department of Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece.
Br J Clin Pharmacol. 2018 Oct;84(10):2405-2414. doi: 10.1111/bcp.13699. Epub 2018 Jul 28.
Recent data suggest that antidepressants are associated with incident diabetes but the possible pharmacological mechanism is still questioned. The aim of the present study was to evaluate antidepressant's risk for reporting diabetes using disproportionality analysis of the FDA adverse events spontaneous reporting system (FAERS) database and to investigate possible receptor/transporter mechanisms involved.
Data from 2004 to 2017 were analysed using OpenVigil2 and adjusted reporting odds ratio (aROR) for reporting diabetes was calculated for 22 antidepressants. Events included in the narrow scope of the SMQ 'hyperglycaemia/new-onset diabetes mellitus' were defined as cases and all the other events as non-cases. The pharmacodynamic profile was extracted using the PDSP and IUPHAR/BPS databases and the occupancy on receptors (serotonin, alpha adrenoreceptors, dopamine, muscarinic, histamine) and transporters (SERT, NET, DAT) was estimated. The relationship between aROR for diabetes and receptor occupancy was investigated with Pearson's correlation coefficient (r) and univariate linear regression.
Six antidepressants were associated with diabetes: nortriptyline with aROR [95% CI] of 2.01 [1.41-2.87], doxepin 1.97 [1.31-2.97], imipramine 1.82 [1.09-3.06], sertraline 1.47 [1.29-1.68], mirtazapine 1.33 [1.04-1.69] and amitriptyline 1.31 [1.09-1.59]. Strong positive correlation coefficients between occupancy and aROR for diabetes were identified for the receptors M , M , M , M and H .
Most of the tricyclic antidepressants, mirtazapine and sertraline seem to be associated with reporting diabetes in FAERS. Higher degrees of occupancy on muscarinic receptors and H may be a plausible pharmacological mechanism. Further clinical assessment and pharmacovigilance data is needed to validate this potential safety signal.
最近的数据表明，抗抑郁药与新发糖尿病有关，但潜在的药理学机制仍存在争议。本研究旨在通过 FDA 不良事件自发报告系统（FAERS）数据库的不比例分析评估抗抑郁药报告糖尿病的风险，并探讨可能涉及的受体/转运体机制。
使用 OpenVigil2 分析 2004 年至 2017 年的数据，计算 22 种抗抑郁药报告糖尿病的调整报告比值比（aROR）。将“高血糖/新发糖尿病”SMQ 窄范围包括的事件定义为病例，其他所有事件定义为非病例。使用 PDSP 和 IUPHAR/BPS 数据库提取药效学特征，并估计受体（5-羟色胺、α肾上腺素能受体、多巴胺、毒蕈碱、组胺）和转运体（SERT、NET、DAT）的占有率。用 Pearson 相关系数（r）和单变量线性回归研究 aROR 与糖尿病受体占有率之间的关系。
六种抗抑郁药与糖尿病相关：去甲替林 aROR [95%CI]为 2.01 [1.41-2.87]，多塞平 1.97 [1.31-2.97]，丙咪嗪 1.82 [1.09-3.06]，舍曲林 1.47 [1.29-1.68]，米氮平 1.33 [1.04-1.69]和阿米替林 1.31 [1.09-1.59]。受体 M 、M 、M 、M 和 H 占有率与糖尿病 aROR 之间存在很强的正相关系数。
大多数三环类抗抑郁药、米氮平和舍曲林似乎与 FAERS 中报告的糖尿病有关。毒蕈碱受体和 H 的占有率较高可能是一种合理的药理学机制。需要进一步的临床评估和药物警戒数据来验证这一潜在的安全信号。
