Associations of antidepressants and antipsychotics with lipid parameters: Do CYP2C19/CYP2D6 genes play a role? A UK population-based study.
Associations of antidepressants and antipsychotics with lipid parameters: Do CYP2C19/CYP2D6 genes play a role? A UK population-based study.
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DOI：
10.1177/02698811231152748
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发表时间：
2023-04
影响因子：
4.1
通讯作者：
Bramon, Elvira
中科院分区：
文献类型：
--
作者：
Richards-Belle, Alvin;Austin-Zimmerman, Isabelle;Wang, Baihan;Zartaloudi, Eirini;Cotic, Marius;Gracie, Caitlin;Saadullah Khani, Noushin;Wannasuphoprasit, Yanisa;Wronska, Marta;Dawda, Yogita;Osborn, David P. J.;Bramon, Elvira
血脂异常是严重精神疾病患者的一个重要心血管风险因素，导致过早死亡。抗精神病药物和血脂异常之间的联系是明确的，而抗抑郁药的证据是混合的。研究抗抑郁药/抗精神病药的使用是否与英国生物样本库参与者的血脂参数相关，以及CYP 2C 19和CYP 2D 6遗传变异是否起作用。对自我报告的处方药进行审查，确定了服用抗抑郁药/抗精神病药的受试者。来自血液样本的总、低和高密度脂蛋白胆固醇（L/HDL-C）和甘油三酯。根据遗传数据分配CYP 2C 19和CYP 2D 6代谢表型。线性回归研究了目标，并针对关键协变量进行了调整。在469，739名参与者中，36，043人服用抗抑郁药（53%女性，中位年龄58岁，17%服用降胆固醇药物），3255人服用抗精神病药（58%女性，中位年龄57岁，27%服用降胆固醇药物）。与未服用每种药物的受试者相比，阿米替林、氟西汀、西酞普兰/艾司西酞普兰、舍曲林、帕罗西汀和文拉法辛的使用与总胆固醇、LDL-C和甘油三酯升高以及HDL-C降低之间存在显著相关性。文拉法辛与最差的血脂相关（总胆固醇，校正平均差异：0.21 mmol/L，95%置信区间（CI）：0.17至0.26，p < 0.001）。抗精神病药物的使用与低HDL-C和高甘油三酯显著相关。在服用舍曲林的受试者中，与正常代谢者相比，CYP 2C 19中间代谢者的HDL-C较高（0.05 mmol/L，95% CI：0.01至0.09，p = 0.007），甘油三酯较低（−0.17 mmol/L，95% CI：−0.29至−0.05，p = 0.007）。抗抑郁药与不良血脂谱显著相关，可能导致基线和定期监测。进一步的研究应调查潜在的机制途径的CYP 2C 19中间代谢表型对HDL-C和甘油三酯的人服用舍曲林的保护作用。
Dyslipidaemia is an important cardiovascular risk factor for people with severe mental illness, contributing to premature mortality. The link between antipsychotics and dyslipidaemia is well established, while evidence on antidepressants is mixed. To investigate if antidepressant/antipsychotic use was associated with lipid parameters in UK Biobank participants and if CYP2C19 and CYP2D6 genetic variation plays a role. Review of self-reported prescription medications identified participants taking antidepressants/antipsychotics. Total, low-, and high-density lipoprotein cholesterol (L/HDL-C) and triglycerides derived from blood samples. CYP2C19 and CYP2D6 metabolic phenotypes were assigned from genetic data. Linear regression investigated aims, adjusted for key covariates. Of 469,739 participants, 36,043 took antidepressants (53% female, median age 58, 17% taking cholesterol-lowering medications) and 3255 took antipsychotics (58% female, median age 57, 27% taking cholesterol-lowering medications). Significant associations were found between use of each amitriptyline, fluoxetine, citalopram/escitalopram, sertraline, paroxetine and venlafaxine with higher total cholesterol, LDL-C, and triglycerides and lower HDL-C, compared to participants not taking each medication. Venlafaxine was associated with the worst lipid profile (total cholesterol, adjusted mean difference: 0.21 mmol/L, 95% confidence interval (CI): 0.17 to 0.26, p < 0.001). Antipsychotic use was significantly associated with lower HDL-C and higher triglycerides. In participants taking sertraline, CYP2C19 intermediate metabolisers had higher HDL-C (0.05 mmol/L, 95% CI: 0.01 to 0.09, p = 0.007) and lower triglycerides (−0.17 mmol/L, 95% CI: −0.29 to −0.05, p = 0.007), compared to normal metabolisers. Antidepressants were significantly associated with adverse lipid profiles, potentially warranting baseline and regular monitoring. Further research should investigate the mechanistic pathways underlying the protective effects of the CYP2C19 intermediate metaboliser phenotype on HDL-C and triglycerides in people taking sertraline.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
2.1
作者：
Conomos MP;Miller MB;Thornton TA
通讯作者：
Thornton TA
影响因子：
6.7
作者：
Cicali EJ;Elchynski AL;Cook KJ;Houder JT;Thomas CD;Smith DM;Elsey A;Johnson JA;Cavallari LH;Wiisanen K
通讯作者：
Wiisanen K
影响因子：
6.7
作者：
Gaedigk, A.;Simon, S. D.;Leeder, J. S.
通讯作者：
Leeder, J. S.
影响因子：
9.8
作者：
Browning, Brian L.;Zhou, Ying;Browning, Sharon R.
通讯作者：
Browning, Sharon R.