Preskorn Sheldon H
PRESKORN: University of Kansas School of Medicine-Wichita and Kansas University-Wichita Clinical Trials Unit.
J Psychiatr Pract. 2014 Mar;20(2):133-7. doi: 10.1097/01.pra.0000445247.54048.68.
In this column, the first in a series discussing why therapeutic drug monitoring (TDM) is a seriously underutilized tool in psychiatry, the author explains why standard antidepressant registration trials are not able to establish a correlation between antidepressant response and the plasma concentration of biogenic amine antidepressants, such as selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. The problem is that such studies have a poor signal-to- noise ratio. In such studies, approximately one third of participants receiving drug respond specifically because of the drug, one third of participants receiving drug respond not because of the drug but rather because of the "placebo" effect inherent in participating in such a study, and one third of participants on drug do not respond sufficiently to be counted as responders. In analyzing the results of such studies, the data from these last two groups make it impossible to identify whether there is any relationship between drug concentration and antidepressant response. The next column in this series will discuss how TDM can be used as a "personalized medicine" tool to evaluate patients who are at risk for less than optimum response either because they may have much more rapid or much slower clearance of a drug than is usual as well as to identify adherence problems.
在本专栏（这是关于探讨为何治疗药物监测（TDM）在精神病学领域严重未得到充分利用的系列文章中的第一篇）中，作者解释了为何标准的抗抑郁药物注册试验无法确立抗抑郁反应与生物胺类抗抑郁药（如选择性5-羟色胺再摄取抑制剂和5-羟色胺-去甲肾上腺素再摄取抑制剂）血浆浓度之间的相关性。问题在于此类研究的信噪比很低。在此类研究中，大约三分之一接受药物治疗的参与者出现特定反应是因为药物本身，三分之一接受药物治疗的参与者出现反应并非因为药物，而是因为参与此类研究所固有的“安慰剂”效应，另外三分之一接受药物治疗的参与者反应不足，不能算作有反应者。在分析此类研究结果时，后两组的数据使得无法确定药物浓度与抗抑郁反应之间是否存在任何关系。本系列的下一篇专栏文章将讨论如何将TDM用作“个性化医疗”工具，以评估那些因药物清除速度可能比正常情况快得多或慢得多而有反应欠佳风险的患者，以及识别依从性问题。
