■精神病学治疗的标准方法被称为“照常治疗”(TAU),其中对一组患者进行相同类型的治疗。由于无效和/或药物不良反应(ADR)的发生,TAU通常需要大量的剂量调整和药物变化。这个过程不仅耗时而且昂贵。抗精神病药物通常用于治疗各种精神疾病,例如精神分裂症和情绪障碍。在精神药物治疗中观察到的疗效和ADR的一些个体间差异可以通过抗精神病药物的药代动力学和药效学的遗传变异来解释。通过对与抗精神病药代谢有关的基因进行药物遗传学分析,可以更好地了解(中)功效和可能的ADR。大多数精神药物通过遗传可变的CYP2D6,CYP1A2,CYP3A4和CYP2C19酶代谢。为了证明药物遗传学测试在定制抗精神病药物治疗中的实用性,在本文中,我们介绍了一个患者的案例,在该患者中,药物遗传学方法显著改变了使用抗精神病药的不耐受或无效的常规TAU.
■在此案例报告中,我们介绍了一名60岁的精神病患者,他在利培酮治疗期间患有严重的锥体外系症状和恶性精神抑制综合征,氟奋乃静,阿立哌唑,布立哌唑,还有奥氮平.因此,我们通过对处方抗精神病药物的药代动力学途径中涉及的基因中的常见功能变体进行基因分型来进行药物遗传学分析,即,CYP2D6、CYP3A4、CYP3A5、CYP1A2、ABCB1和ABCG2。根据荷兰药物遗传学工作组(DPWG)或临床药物遗传学实施联盟(CPIC)提供的基于证据的药物遗传学建议,提出了药物-基因对的治疗建议。
■药物遗传学测试揭示了患者的特定代谢特征和药代动力学表型,回想起来,这为观察到的ADR提供了可能的解释。根据药物遗传学结果,事实证明,选择有效和安全的药物要容易得多。治疗后精神病症状消失,而阴性症状持续的程度较小。
■根据案例,我们已经证明,考虑到患者的药物遗传学特征可以解释抗精神病药物治疗的反应和相关副作用。此外,药物遗传学检测可以在知情的情况下选择最合适的药物和最佳剂量调整.这种方法可以避免或最小化潜在的严重剂量相关不良反应和治疗无效。然而,由于精神病理学的复杂性和该领域使用的多重药物,进一步进行药代动力学和药物遗传学研究以更好地评估基因-药物和基因-基因-药物相互作用非常重要。
UNASSIGNED: The standard approach to treatment in psychiatry is known as \"treatment as usual\" (TAU), in which the same types of treatment are administered to a group of patients. TAU often requires numerous dose adjustments and medication changes due to ineffectiveness and/or the occurrence of adverse drug reactions (ADRs). This process is not only time-consuming but also costly. Antipsychotic medications are commonly used to treat various psychiatric disorders such as schizophrenia and mood disorders. Some of the inter-individual differences in efficacy and ADRs observed in psychopharmacotherapy can be explained by genetic variability in the pharmacokinetics and pharmacodynamics of antipsychotics. A better understanding of (in)efficacy and possible ADRs can be achieved by pharmacogenetic analysis of genes involved in the metabolism of antipsychotics. Most psychotropic drugs are metabolized by genetically variable CYP2D6, CYP1A2, CYP3A4, and CYP2C19 enzymes. To demonstrate the utility of pharmacogenetic testing for tailoring antipsychotic treatment, in this paper, we present the
case of a patient in whom a pharmacogenetic approach remarkably altered an otherwise intolerant or ineffective conventional TAU with antipsychotics.
UNASSIGNED: In this
case report, we present a 60-year-old patient with psychotic symptoms who suffered from severe extrapyramidal symptoms and a malignant neuroleptic syndrome during treatment with risperidone, fluphenazine, aripiprazole, brexpiprazole, and olanzapine. Therefore, we performed a pharmacogenetic analysis by genotyping common functional variants in genes involved in the pharmacokinetic pathways of prescribed antipsychotics, namely, CYP2D6, CYP3A4, CYP3A5, CYP1A2, ABCB1, and ABCG2. Treatment recommendations for drug-gene pairs were made according to available evidence-based pharmacogenetic recommendations from the Dutch Pharmacogenetics Working Group (DPWG) or Clinical Pharmacogenetics Implementation Consortium (CPIC).
UNASSIGNED: Pharmacogenetic testing revealed a specific metabolic profile and pharmacokinetic phenotype of the patient, which in retrospect provided possible explanations for the observed ADRs. Based on the pharmacogenetic results, the choice of an effective and safe medication proved to be much easier. The psychotic symptoms disappeared after treatment, while the negative symptoms persisted to a lesser extent.
UNASSIGNED: With the
case presented, we have shown that taking into account the pharmacogenetic characteristics of the patient can explain the response to antipsychotic treatment and associated side effects. In addition, pharmacogenetic testing enabled an informed choice of the most appropriate drug and optimal dose adjustment. This approach makes it possible to avoid or minimize potentially serious dose-related ADRs and treatment ineffectiveness. However, due to the complexity of psychopathology and the polypharmacy used in this field, it is of great importance to conduct further pharmacokinetic and pharmacogenetic studies to better assess gene-drug and gene-gene-drug interactions.