Improved Antidepressant Remission in Major Depression via a Pharmacokinetic Pathway Polygene Pharmacogenetic Report.
Improved Antidepressant Remission in Major Depression via a Pharmacokinetic Pathway Polygene Pharmacogenetic Report.
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DOI：
10.9758/cpn.2015.13.2.150
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发表时间：
2015-08-31
期刊：
影响因子：
--
通讯作者：
Singh AB
中科院分区：
文献类型：
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作者：
Singh AB
预计到2030年，重度抑郁症（MDD）将成为全球致残的主要原因。只有少数患者服用抗抑郁药后病情好转。如果检测影响中枢神经系统（CNS）生物利用度的多态性可以指导处方者更有效地给患者用药，缓解率可能会提高，MDD的疾病负担也会减少。肝和血脑屏障（BBB）多态性似乎影响抗抑郁药中枢神经系统的生物利用度。对高加索成年重度抑郁症患者（n=148）进行了一项为期12周的前瞻性双盲随机遗传指导与非遗传指导的抗抑郁药物剂量试验。接受遗传指导处方的受试者有2.52倍的缓解机会（95%可信区间[CI]= 1.71-3.73, z=4.66, p<0.0001）。基因型(NNG)=3所需的数量（95% CI= 1.7-3.5）产生额外的缓解。这些数据表明，药理学剂量报告（CNSDose®）可提高抗抑郁药的疗效。效应量是足够的，如果结果是独立复制的，可能会出现转化为临床护理。
Major depressive disorder (MDD) is projected to be a leading cause of disability globally by 2030. Only a minority of patients remit with antidepressants. If assay of polymorphisms influencing central nervous system (CNS) bioavailability could guide prescribers to more effectively dose patients, remission rates may improve and the burden of disease from MDD reduce. Hepatic and blood brain barrier (BBB) polymorphisms appear to influence antidepressant CNS bioavailability. A 12-week prospective double blind randomized genetically guided versus unguided trial of antidepressant dosing in Caucasian adults with MDD (n=148) was conducted. Subjects receiving genetically guided prescribing had a 2.52-fold greater chance of remission (95% confidence interval [CI]=1.71–3.73, z=4.66, p<0.0001). The number needed to genotype (NNG)=3 (95% CI=1.7–3.5) to produce an additional remission. These data suggest that a pharmacogenetic dosing report (CNSDose®) improves antidepressant efficacy. The effect size was sufficient that translation to clinical care may arise if results are independently replicated.