Data_Sheet_1_Therapeutic Reference Ranges for Psychotropic Drugs: A Protocol for Systematic Reviews.docx

Background: For many psychotropic drugs, monitoring of drug concentrations in the blood (Therapeutic Drug Monitoring; TDM) has been proven useful to individualize treatments and optimize drug effects. Clinicians hereby compare individual drug concentrations to population-based reference ranges for a titration of prescribed doses. Thus, established reference ranges are pre-requisite for TDM. For psychotropic drugs, guideline-based ranges are mostly expert recommendations derived from a conglomerate of cohort and cross-sectional studies. A systematic approach for identifying therapeutic reference ranges has not been published yet. This paper describes how to search, evaluate and grade the available literature and validate published therapeutic reference ranges for psychotropic drugs.Methods/Results: Following PRISMA guidelines, relevant databases have to be systematically searched using search terms for the specific psychotropic drug, blood concentrations, drug monitoring, positron emission tomography (PET) and single photon emission computed tomography (SPECT). The search should be restricted to humans, and diagnoses should be pre-specified. Therapeutic references ranges will not only base upon studies that report blood concentrations in relation to clinical effects, but will also include implications from neuroimaging studies on target engagement. Furthermore, studies reporting concentrations in representative patient populations are used to support identified ranges. Each range will be assigned a level of underlying evidence according to a systematic grading system.Discussion: Following this protocol allows a comprehensive overview of TDM literature that supports a certain reference range for a psychotropic drug. The assigned level of evidence reflects the validity of a reported range rather than experts' opinions.

背景：对于众多精神活性药物，血液中药物浓度（治疗药物监测；TDM）的监控已被证实有助于个体化治疗方案并优化药物疗效。临床医生据此将个体药物浓度与基于人群的参考范围进行对比，以调整处方剂量。因此，已建立的参考范围是TDM的先决条件。对于精神活性药物，基于指南的参考范围大多为专家基于队列研究和横断面研究综合得出的建议。尚未发表关于识别治疗参考范围的系统性方法。本文描述了如何检索、评估和分级现有文献，并验证已发表的针对精神活性药物的治疗参考范围。方法/结果：遵循PRISMA指南，需系统性地使用针对特定精神活性药物、血液浓度、药物监测、正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）的搜索词检索相关数据库。搜索应限于人类研究对象，且诊断需预先指定。治疗参考范围不仅基于报告与临床效果相关的血液浓度研究，还将包括关于靶点结合的神经影像学研究的影响。此外，报告代表性患者群体中浓度的研究也被用于支持确定的范围。每个范围将根据系统性分级系统分配一个潜在证据级别。讨论：遵循此方案可全面概述支持特定精神活性药物参考范围的TDM文献。所分配的证据级别反映了报告范围的有效性，而非专家意见。