Fundació Docència i Recerca Mútua Terrassa, Terrassa, Spain.
Centro de Investigación en Red de Salud Mental, CIBERSAM, Madrid, Spain.
Transl Psychiatry. 2019 Jul 25;9(1):177. doi: 10.1038/s41398-019-0511-9.
Antipsychotic drugs fail to achieve adequate response in 30-50% of treated patients and about 50% of them develop severe and lasting side effects. Treatment failure results in poorer prognosis with devastating repercussions for the patients, carers and broader society. Our study evaluated the clinical benefits of a pharmacogenetic intervention for the personalisation of antipsychotic treatment. Pharmacogenetic information in key CYP polymorphisms was used to adjust clinical doses in a group of patients who started or switched treatment with antipsychotic drugs (PharmG+, N = 123), and their results were compared with those of a group of patients treated following existing clinical guides (PharmG-, N = 167). There was no evidence of significant differences in side effects between the two arms. Although patients who had their antipsychotic dose adjusted according to CYPs polymorphisms (PharmG+) had a bigger reduction in side effects than those treated as usual (PharmG-), the difference was not statistically significant (p > 0.05 for all comparisons). However, PharmG+ patients treated with CYP2D6 substrates that were carriers of CYP2D6 UMs or PMs variants showed a significantly higher improvement in global, psychic and other UKU side effects than PharmG- patients (p = 0.02, p = 0.05 and p = 0.01, respectively). PharmG+ clozapine treated patients with CYP1A2 or CYP2C19 UM and PMs variants also showed higher reductions in UKU scores than PharmG- clozapine patients in general. However, those differences were not statistically significant. Pharmacogenetic interventions may improve the safety of antipsychotic treatments by reducing associated side effects. This intervention may be particularly useful when considering treatment with antipsychotics with one major metabolic pathway, and therefore more susceptible to be affected by functional variants of CYP enzymes.
抗精神病药物在 30-50%的治疗患者中未能达到充分反应，其中约 50%的患者出现严重且持久的副作用。治疗失败导致预后较差，给患者、护理人员和更广泛的社会带来破坏性影响。我们的研究评估了药物遗传学干预对抗精神病治疗个体化的临床益处。关键 CYP 多态性的药物遗传学信息用于调整开始或转换抗精神病药物治疗的一组患者的临床剂量（PharmG+，N=123），并将其结果与一组根据现有临床指南治疗的患者（PharmG-，N=167）进行比较。两组之间的副作用没有证据表明存在显著差异。尽管根据 CYP 多态性调整抗精神病药物剂量的患者（PharmG+）比常规治疗的患者（PharmG-）的副作用减少幅度更大，但差异无统计学意义（所有比较的 p 值均>0.05）。然而，PharmG+患者治疗 CYP2D6 底物时，如果是 CYP2D6 UMs 或 PMs 变体的携带者，在全球、精神和其他 UKU 副作用方面的改善明显高于 PharmG-患者（p=0.02，p=0.05 和 p=0.01，分别）。PharmG+氯氮平治疗 CYP1A2 或 CYP2C19 UMs 和 PMs 变体的患者，在 UKU 评分降低方面也明显优于 PharmG-氯氮平患者，但差异无统计学意义。药物遗传学干预可能通过减少相关副作用来提高抗精神病药物治疗的安全性。当考虑使用一种主要代谢途径的抗精神病药物治疗时，这种干预可能特别有用，因为这些药物更容易受到 CYP 酶功能变体的影响。
