Anderson George M, Bruno-Pacella Isabella
The Child Study Center and the Department of Laboratory Medicine, Yale University School of Medicine, 230 S. Frontage Rd, New Haven, CT, 06519, USA.
Connecticut College, New London, CT, USA.
Psychopharmacology (Berl). 2023 Jan;240(1):1-13. doi: 10.1007/s00213-022-06276-5. Epub 2022 Nov 18.
Assessment of the bioeffect of serotonin reuptake inhibitors (SRIs, including both selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)) at the serotonin transporter (SERT) in patients and healthy controls can have important theoretical and clinical implications.
Bioeffect at SERT has been assessed by neuroimaging of brain SERT occupancy, through in vitro measurements of platelet serotonin (5-HT) uptake, and by measuring platelet 5-HT content pre- and post-initiation of SRI administration. Studies of platelet 5-HT content were reviewed in order to (1) determine the overall apparent bioeffect of SRIs; (2) compare bioeffect across types of SRIs; (3) compare the three approaches to assessing SRI bioeffect; and (4) determine how the findings might inform clinical practice.
We performed a systematic review of the published studies that measured platelet 5-HT content to assess SRI bioeffect at the platelet SERT. Studies using neuroimaging and in vitro platelet 5-HT uptake to assess SRI bioeffect were reviewed for comparison purposes.
Clinical doses of SRIs typically resulted in 70-90% reductions in platelet 5-HT content. The observed bioeffect at the platelet SERT appeared similar among different SSRIs and SNRIs. The bioeffect estimations based on platelet 5-HT content were consistent with those obtained using neuroimaging to assess brain SERT occupancy and those based on the in vitro measurement of platelet 5-HT uptake.
In general, excellent agreement was seen in the apparent SRI bioeffect (70-90% inhibition) among the platelet 5-HT content studies and across the three bioeffect approaches. Theoretical and practical clinical implications are discussed.
评估5-羟色胺再摄取抑制剂（SRIs，包括选择性5-羟色胺再摄取抑制剂（SSRIs）和5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRIs））对患者及健康对照者5-羟色胺转运体（SERT）的生物效应，具有重要的理论和临床意义。
通过脑SERT占有率的神经影像学检查、血小板5-羟色胺（5-HT）摄取的体外测量以及测量SRI给药前后的血小板5-HT含量，对SERT的生物效应进行评估。对血小板5-HT含量的研究进行综述，以便（1）确定SRIs的总体表观生物效应；（2）比较不同类型SRIs的生物效应；（3）比较评估SRI生物效应的三种方法；（4）确定这些发现如何为临床实践提供参考。
我们对已发表的测量血小板5-HT含量以评估血小板SERT处SRI生物效应的研究进行了系统综述。为作比较，对使用神经影像学和体外血小板5-HT摄取评估SRI生物效应的研究也进行了综述。
SRI的临床剂量通常会使血小板5-HT含量降低70-90%。不同的SSRIs和SNRIs在血小板SERT处观察到的生物效应似乎相似。基于血小板5-HT含量的生物效应估计值与使用神经影像学评估脑SERT占有率以及基于体外测量血小板5-HT摄取所获得的估计值一致。
总体而言，血小板5-HT含量研究之间以及三种生物效应评估方法之间，在SRI的表观生物效应（70-90%抑制）方面具有高度一致性。文中讨论了其理论和实际临床意义。
