Pham Mia, Caglayan Aydin
General Internal Medicine, St. George's Hospital, London, GBR.
General Surgery, Medway NHS Foundation Trust, London, GBR.
Cureus. 2024 Jul 24;16(7):e65279. doi: 10.7759/cureus.65279. eCollection 2024 Jul.
Some patients with schizophrenia fail to respond to standard antipsychotics and are considered treatment-resistant. In these cases, clozapine is the only antipsychotic with proven efficacy, but its use is complicated by severe adverse effects, complex monitoring requirements, and non-response. Variation within the CYP450 enzymes CYP1A2, CYP2D6, CYP3A4, and CYP2C19 has been linked to the differential metabolism of antipsychotics. Testing for CYP450 single nucleotide polymorphisms may be a useful predictor of treatment resistance and could inform pharmacogenetic recommendations to identify potential treatment non-responders. Nonetheless, it remains uncertain whether differential antipsychotic metabolism is directly related to treatment efficacy. This comprehensive narrative review endeavours to delve into the molecular and genetic basis of schizophrenia, and discuss the current treatments available. In particular, we aim to examine the aetiology of treatment resistance in schizophrenia through available literature and discuss current challenges within the field.
一些精神分裂症患者对标准抗精神病药物无反应，被认为是难治性的。在这些情况下，氯氮平是唯一经证实有效的抗精神病药物，但其使用因严重不良反应、复杂的监测要求和无反应而变得复杂。细胞色素P450（CYP450）酶CYP1A2、CYP2D6、CYP3A4和CYP2C19的变异与抗精神病药物的代谢差异有关。检测CYP450单核苷酸多态性可能是治疗抵抗的有用预测指标，并可为药物遗传学建议提供依据，以识别潜在的治疗无反应者。尽管如此，抗精神病药物代谢差异是否与治疗效果直接相关仍不确定。这篇全面的叙述性综述旨在深入探讨精神分裂症的分子和遗传基础，并讨论现有的治疗方法。特别是，我们旨在通过现有文献研究精神分裂症治疗抵抗的病因，并讨论该领域当前的挑战。
