Towards the clinical implementation of pharmacogenetics in bipolar disorder.
Towards the clinical implementation of pharmacogenetics in bipolar disorder.
复制标题
致力于在躁郁症中进行药物遗传学的临床实施。
DOI：
10.1186/1741-7015-12-90
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发表时间：
2014-05-30
期刊：
影响因子：
9.3
通讯作者：
Kelsoe JR
中科院分区：
文献类型：
--
作者：
Salloum NC;McCarthy MJ;Leckband SG;Kelsoe JR
双相情感障碍（BD）是一种精神疾病，其定义为躁狂和抑郁情绪状态之间的病理变化，导致残疾，增加医疗费用并增加自杀风险。尽管存在有效的BD治疗方法，但结果的可变性会导致大量治疗失败，通常随后会经历可能需要数年时间的药物转换试错过程。药物遗传学测试（PGT），通过定制药物选择到一个人，可以个性化和加快治疗，以便更快地确定药物非常适合个别BD患者。在BD中，药物反应表型和特定遗传标记物之间存在许多关联。然而，到目前为止，PGT的临床应用仍然有限，经常引用在广泛应用之前必须回答的问题。这些问题包括：支持性证据的要求是什么？临床相关影响有多大？需要何种程度的特异性和敏感性？给定的标记物是否影响决策并具有临床实用性？在许多情况下，这些问题的答案仍然是未知的，最终，PGT是否有效和有用的问题必须根据经验来确定。为此，我们回顾了文献，并选择了在BD中具有最强有力证据的药物基因型相关性。基于这些发现，我们提出了一种用于PGT的初步小组，以及一种可以将PGT小组的结果整合用于临床解释的方法。最后，我们认为，基于足够的积累的证据，PGT实施的研究，现在是必要的。我们提出并讨论了随机临床试验的设计，以测试使用PGT治疗BD。
Bipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients. A number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD. Based upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD.
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DOI：
10.1016/j.pnpbp.2013.03.005
发表时间：
2013-07-01
影响因子：
5.6
作者：
Calati, Raffaella;Crisafulli, Concetta;Mendlewicz, Julien
通讯作者：
Mendlewicz, Julien
影响因子：
30.8
作者：
Chambers, John C.;Elliott, Paul;Kooner, Jaspal S.
通讯作者：
Kooner, Jaspal S.
影响因子：
5.3
作者：
Berghoefer, Anne;Alda, Martin;Pfennig, Andrea
通讯作者：
Pfennig, Andrea
影响因子：
30.8
作者：
Binder, EB;Salyakina, D;Muller-Myhsok, B
通讯作者：
Muller-Myhsok, B
影响因子：
6.7
作者：
Brockmöller, J;Kirchheiner, J;Roots, I
通讯作者：
Roots, I