Khorassani Farah, Azevedo Ricardo, Farokhpay Reza
University of California, Irvine, School of Pharmacy and Pharmaceutical Sciences, 802 W Peltason Dr, Irvine, CA, 92617, USA.
University of California, Irvine, School of Medicine, 1001 Health Sciences Road, Irvine, CA, 92697, USA.
BMC Psychiatry. 2024 Dec 4;24(1):885. doi: 10.1186/s12888-024-06319-5.
Strong evidence for therapeutic drug monitoring exists for olanzapine and clozapine, however, olanzapine therapeutic drug monitoring is often underutilized. Evidence for pharmacogenomic-guided dosing of antipsychotics is not as robust, especially for cytochrome P450 1A2 metabolized agents such as olanzapine and clozapine. Herein, we present a case involving a patient suspected of having poor CYP1A2 metabolism. Therapeutic drug monitoring of olanzapine was employed to guide the titration of clozapine following olanzapine failure. Despite pursuing pharmacogenetic testing, no meaningful results were obtained due to the omission of CYP1A2 variants associated with poor metabolism.
A 32-year-old Caucasian male with schizoaffective disorder-bipolar type, ADHD, and autism spectrum disorder presented with extrapyramidal symptoms due to antipsychotic polypharmacy, resulting in multiple falls. He experienced a partial response to olanzapine 40 mg, thus his dose was increased to 50 mg. Sampling an olanzapine trough revealed a supratherapeutic level of 152 ng/mL. Given his history of EPS and other reported adverse effects from antipsychotics, including clozapine, pharmacogenomic testing was pursued. The patient cross-tapered to clozapine slowly, with the knowledge that the patient would likely exhibit elevated levels of olanzapine. Clozapine was efficacious and tolerated well. As expected, the patient exhibited higher clozapine trough concentrations for someone of his age, ethnicity, and gender. Pharmacogenomic testing yielded no relevant findings relating to olanzapine or clozapine metabolism.
This case highlights the utility of TDM over pharmacogenetic testing for patients on these medications with a suspected alteration in CYP1A2 metabolism. therapeutic drug monitoring emerges as a more practical approach with stronger evidence for its use, particularly in cases of suspected reduced CYP1A2 activity, where suballeles resulting in decreased enzyme function are not readily detectable on standard commercial pharmacogenomic panels.
对于奥氮平和氯氮平，有强有力的证据支持治疗药物监测，然而，奥氮平治疗药物监测的应用常常不足。抗精神病药物的药物基因组学指导给药的证据并不那么充分，尤其是对于细胞色素P450 1A2代谢的药物，如奥氮平和氯氮平。在此，我们呈现一个涉及疑似CYP1A2代谢不良患者的病例。在奥氮平治疗失败后，采用奥氮平治疗药物监测来指导氯氮平的滴定。尽管进行了药物基因组学检测，但由于遗漏了与代谢不良相关的CYP1A2变体，未获得有意义的结果。
一名32岁患有双相型分裂情感障碍、注意力缺陷多动障碍和自闭症谱系障碍的白人男性，因联用多种抗精神病药物出现锥体外系症状，导致多次跌倒。他对40毫克奥氮平有部分反应，因此剂量增加到50毫克。奥氮平谷浓度采样显示超治疗水平为152纳克/毫升。鉴于他有锥体外系反应病史以及其他抗精神病药物（包括氯氮平）报告的不良反应，进行了药物基因组学检测。患者在知晓其奥氮平水平可能升高的情况下，缓慢交叉减量至氯氮平。氯氮平有效且耐受性良好。正如预期的那样，该患者的氯氮平谷浓度高于同年龄、种族和性别的其他人。药物基因组学检测未得出与奥氮平或氯氮平代谢相关的相关结果。
该病例突出了治疗药物监测相对于药物基因组学检测对这些疑似CYP1A2代谢改变的用药患者的实用性。治疗药物监测成为一种更实用的方法，有更强的使用证据，特别是在疑似CYP1A2活性降低的情况下，在标准商业药物基因组学检测板上不容易检测到导致酶功能降低的亚等位基因。
