Department of Psychiatry and Psychotherapy, University Medical Center of Mainz, Germany.
Pharmacopsychiatry. 2011 Sep;44(6):195-235.
Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from “strongly recommended” to “potentially useful”. Evidence-based “therapeutic reference ranges” and “dose related reference ranges” were elaborated after an extensive literature search and a structured internal review process. A “laboratory alert level” was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint eff ort.
治疗药物监测（therapeutic drug monitoring，TDM），即定量检测血清或血浆中的药物浓度以优化剂量，已被证明是一种非常有价值的工具，可用于个体化的精神药理学治疗。当存在药物服用不确定、不耐受、治疗剂量无反应或药物-药物相互作用等情况时，测量药物浓度有助于确定问题所在。在精神医学领域，可能主要从 TDM 中受益的患者人群包括儿童、孕妇、老年患者、智力障碍患者、法医患者、已知或疑似存在遗传决定的药代动力学异常的患者或存在与药代动力学相关合并症的患者。然而，只有当 TDM 方法充分融入临床治疗过程时，才能获得优化药物治疗的潜在益处。为了促进 TDM 的合理应用，德国神经精神药理学和精神药理学协会（Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie，AGNP）的 TDM 专家组于 2004 年发布了精神医学 TDM 指南。此后，相关知识取得了显著进展，并且引入了新的精神药理学药物，这些药物也可作为 TDM 的候选药物。因此，对 TDM 共识指南进行了更新和扩展，涵盖了 128 种神经精神药物。根据推荐级别，将 TDM 的应用分为“强烈推荐”至“可能有用”四个级别。在广泛的文献检索和结构化内部审查过程之后，制定了基于证据的“治疗参考范围”和“剂量相关参考范围”。引入了“实验室警示水平”，即实验室应立即将其通知治疗医生的血浆水平。还提供了有关药物细胞色素 P450 底物和抑制剂特性、药物代谢产物与母体药物浓度比值的正常范围以及解释服务建议的支持信息。还提供了何时将 TDM 与药物遗传学检测相结合的建议。遵循这些指南将有助于改善许多患者的精神药物治疗效果，尤其是在存在药代动力学问题的情况下。因此，人们永远不应忘记 TDM 是一项跨学科任务，有时需要尊重地讨论看似不一致的数据，以便最终使患者从这种共同努力中受益。
